Project

Complexity in Medicine: Practical Problems, Their Definitions, Models, and Solutions

Goal: Have you ever thought about doing biomedical research differently? Had you ever wondered about the complicatedness of the body functioning? Do you feel lost in all available data? Then you are at the right place where you can discover research, medical methods, and mathematics capable to help you and others.

Medicine is facing on many scales of its functioning real-world challenges that are beyond linear, mechanistic thinking and solutions. It is getting gradually revealed that the complexity of our bodies is much greater than we thought before. We know that we function as networks of networks of biological processes. It is becoming gradually known that our own bodies are ecosystems immersed in higher-level ecosystems. This all is potentiated by increasing complexity of medical care itself.

We are looking for a better understanding of medicine and the challenges that it is currently facing. One of the most promising tools capable to shed light on this convoluted structure of mutually entangled processes is provided by complexity, self-organization, emergence, self-repair, and beyond.

Briefly explained, complexity is a fast-developing research area sitting at the borders of mathematics, computational mathematics, computer science, and related scientific areas that enables us to solve challenges that were sofar intractable. Problems of the same grade, as the medicine itself is facing, are known from other scientific disciplines: this is the source to learn.

This project heavily relies on a tight cooperation of medical doctors, biomedical researchers, computer scientists, and mathematicians. No one working in complexity as a single discipline is capable to grasp it as the whole and to solve such kinds of very diverse problems on his/her own.

Together in tight cooperation, we can gradually gain a greater insight into this extremely challenging task. It is a long term project. We are aware of the fact that it will take decades to develop the right understanding and machinery.

There is a lot of work, beautiful work, in front of us. :-)

Methods: Medicine, Psychology, Physiological Processes, Stress, Complexity Theory, Traditional Medicine, Methodology, Healing, Mathematics

Date: 7 March 2020

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Jiří Kroc
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Gaetan Chevalier, Stephen T. Sinatra, James L. Oschman, PhD & Richard M. Delany
THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE 19:2 (2013) 102–110
DOI: 10.1089/acm.2011.0820
Abstract Objectives: Emerging research is revealing that direct physical contact of the human body with the surface of the earth (grounding or earthing) has intriguing effects on human physiology and health, including beneficial effects on various cardiovascular risk factors. This study examined effects of 2 hours of grounding on the electrical charge (zeta potential) on red blood cells (RBCs) and the effects on the extent of RBC clumping. Design/interventions: Subjects were grounded with conductive patches on the soles of their feet and palms of their hands. Wires connected the patches to a stainless-steel rod inserted in the earth outdoors. Small fingertip pinprick blood samples were placed on microscope slides and an electric field was applied to them. Electrophoretic mobility of the RBCs was determined by measuring terminal velocities of the cells in video recordings taken through a microscope. RBC aggregation was measured by counting the numbers of clustered cells in each sample. Settings/location: Each subject sat in a comfortable reclining chair in a soundproof experiment room with the lights dimmed or off. Subjects: Ten (10) healthy adult subjects were recruited by word-of-mouth. Results: Earthing or grounding increased zeta potentials in all samples by an average of 2.70 and significantly reduced RBC aggregation. Conclusions: Grounding increases the surface charge on RBCs and thereby reduces blood viscosity and clumping. Grounding appears to be one of the simplest and yet most profound interventions for helping reduce cardiovascular risk and cardiovascular events.
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Conclusions
Increased blood viscosity in the general population may be a predictor of cardiovascular events because of its influences on hypertension, thrombogenesis, ischemia, and arthrogenesis. Unfortunately, blood viscosity has become a forgotten risk factor and is rarely measured in clinical practice.45 Interventions that reduce blood viscosity and RBC aggregation are important. Statins appear to be effective for modulating blood viscosity, but can have serious side-effects including death.3 Moreover, some patients have statin intolerance. The use of a safe effective anti-inflammatory strategy that is not dependent on isoprenoid inhibition is therefore desirable. Grounding or earthing the body is virtually harmless. To date, there has been no systematic study of the effects of grounding on BP. However, there are anecdotal reports that patients using blood-thinning drugs, such as warfarin (Coumadin), need to have their clotting time monitored when they begin to make more frequent conductive contact with the earth. When physicians recommend evidencebased, harmless, and simple natural interventions, alleviation of human suffering and improved quality of life can be realized. The findings in this pilot study indicate that grounding has a safe and significant effect on zeta potential and that further study is warranted.
 
Jiří Kroc
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Everyone is welcomed to watch the recording of "Czech Christmas Mass" ("Česká mše vánoční ") composed by Jakub Jan Ryba given in the Saint Vite Cathedral in the Prague Castle in 2010 where Czech kings were crowned.
Enjoy this extraordinary, spirit rejuvenating music.
( concert starts at 5:30 min).  🙏
 
Jiří Kroc
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Gregory D. Sloop, Quirijn De Mast, Gheorghe Pop, Joseph J. Weidman  & John A. St. Cyr
Cureus 12(2): e7090.
DOI 10.7759/cureus.7090
Abstract:
Blood viscosity is increased by elevated concentrations of acute phase reactants and hypergammaglobulinemia in inflammation. These increase blood viscosity by increasing plasma viscosity and fostering erythrocyte aggregation. Blood viscosity is also increased by decreased erythrocyte deformability, as occurs in malaria. Increased blood viscosity contributes to the association of acute infections with myocardial infarction (MI), venous thrombosis, and venous thromboembolism. It also increases vascular resistance, which decreases tissue perfusion and activates stretch receptors in the left ventricle, thereby initiating the systemic vascular resistance response. This compensates for the increased vascular resistance by vasodilation, lowering hematocrit, and decreasing intravascular volume. This physiological response causes the anemias associated with malaria, chronic inflammation, and other chronic diseases. Since tissue perfusion is inversely proportional to blood viscosity, anemia may be beneficial as it increases tissue perfusion when erythrocyte aggregating factors or erythrocytes with decreased deformability are present in the blood.
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Conclusions
Both acute and chronic inflammation has the potential to increase blood viscosity. Because increased blood viscosity increases the risk of thrombosis, a wide variety of infections are associated with MI. Increased blood viscosity decreases tissue perfusion, further increasing the risk of MI, particularly in the presence of pre-existing vascular or lung disease. Because blood is a non-Newtonian fluid, the increase in blood viscosity caused by inflammation is even greater in low-shear conditions in veins, increasing the risk of venous thrombosis. Without negative feedback, increased blood viscosity will cause fatal polycythemia: increased blood viscosity will decrease renal perfusion, which will increase erythropoietin secretion, further increasing viscosity, decreasing perfusion, and so on. The systemic vascular resistance response is the adaptive mechanism that prevents this scenario by decreasing hematocrit and intravascular volume and causing vasodilation. This response causes the anemias associated with malaria and chronic inflammation, thereby reducing blood viscosity and improving tissue perfusion.
 
Jiří Kroc
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Laura Di Lodovico, Stanislas Mondotc, Joël Doréc, Isabelle Mackd, Mouna Hanachia &  Philip Gorwood
Progress in Neuro-Psychopharmacology and Biological Psychiatry 106:2 (2021) 110114
DOI: 10.1016/j.pnpbp.2020.110114
Abstract:
Background
Alterations of gut microbiota may play a role in Anorexia Nervosa (AN) through perturbations of the gut-brain axis. Some studies found differences in the gut microbiota of patients with AN compared to healthy controls, but results are heterogeneous. The aim of this work was to systematically review the existing studies comparing gut microbial composition in AN and healthy controls, and to perform a quantitative synthesis of the pooled clinical and microbiological data, when available.
Methods
A comprehensive literature search was performed to identify human studies investigating relationships between AN and gut microbiota. Microbiome datasets from studies were pooled and analysed focusing on alpha and beta-diversity and the relative abundance of microbial species in patients' gut microbiota compared to healthy controls.
Results
Nine studies were eligible for the systematic review, of which 4 were included in the quantitative synthesis. Preserved alpha-diversity and decreased beta-diversity in AN emerged from the qualitative synthesis, while a slight increase of alpha-diversity (d < 0.4) and comparable beta-diversity were reported by the quantitative synthesis. Out of the 46 common species compared, three had a large combined effect size (d ≥ 0.9) to differentiate patients from controls, namely Alistipes, Parabacterioides and Roseburia. The latter was also correlated with BMI (ρ = 0.29).
Conclusions
The decrease of butyrate-producing species and the increase of mucine-degrading species may represent hallmarks of the gut microbiota alterations in AN, and therefore potentially interesting therapeutic targets. The heterogeneity of clinical and methodological characteristics hampers the generalizability of the results. Standardized research methods could improve comparability among studies to better identify the alterations of gut microbiota in AN.
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From Discussion:
The decrease of relative abundance of Roseburia deserves particular attention. The decrease of this butyrate-producing species had a large effect size due to the homogeneity of results among studies, and largely confirms the findings of previous literature (Mack et al., 2016). Roseburia is a butyrate-producing firmicute playing an important role in the control of gut inflammatory processes (La Rosa et al., 2019), the maintenance of the immune system and in colonic motility (Tamanai- Shacoori et al., 2017). The decrease of the relative abundance of Roseburia in AN is largely responsible for the decrease of SCFA (Borgo et al., 2017). Butyrate, acetate and propionate, products of the fermentation of indigestible carbohydrates in the colon, represent a source of energy for colonocytes and are able to affect cell signalling, neurotransmitter synthesis and release, free radical production, and mitochondrial function (den Besten et al., 2013). Butyrate and propionate also modulate gene expression at the CNS level after crossing the blood- brain-barrier, being inhibitors of histone deacetylase (Borgo et al., 2017), and play a role in appetite regulation by modulating PYY peptide and ghrelin (Byrne et al., 2015). Propionate has metabolic effects such as regulating cholesterol synthesis and gluconeogenesis, while acetate acts as a substrate for lipogenesis. The decrease of the relative abundance of Butyrivibria found in patients with AN may further explain the decrease of faecal butyrate concentration and the increase of functional intestinal symptoms, given its potential in the protection of the gut barrier (Ohkawara et al., 2005). Taken together, these findings indicate decreased butyrate-producing bacteria as potential hallmarks of the gut microbiota in AN and suggest them as targets for prebiotic use to enhance bacterial abundance and butyrate concentrations with potentially beneficial effects on mood, behaviour, appetite regulation and immune balance (Scott et al., 2015). Though no effect was found on weight gain, probiotic administration may exert a beneficial effect on psychopathological aspects of the disease, having provided a significant amelioration of compulsive behaviour in gnotobiotic mice transplanted with stools from patients suffering from AN (Hata et al., 2019).
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Conclusions:
This systematic review and quantitative synthesis on the role of the gut microbiota in AN underlined heterogeneity among studies, with some discrepancies between qualitative and quantitative synthesis, potentially favoured by smoothing the methodological heterogeneities in the analysis of the gut microbiota. The elaboration of standardized recommendations for future research should enhance comparability among studies and allow a generalization of results. Findings such as the decrease of the relative abundance of butyrate producing species, in particular Roseburia, and the increase of Parabacterioides, Alistipes and mucin degrading bacteria such as Akkermansia, and could pave the way to the identification of biomarkers of the gut microbiota of patients with AN and represent important therapeutic targets. The administration of pro- and prebiotics could represent a promising strategy for restoring the gut microbiota of patients suffering from AN.
 
Jiří Kroc
added an update
Pete C. Arambula, Erik Peper, Mitsumasa Kawakami & Katherine Hughes Gibney
Abstract:
This study explores the physiological correlates of a highly practiced Kundalini Yoga meditator. Thoracic and abdominal breathing patterns, heart rate (HR), occipital parietal electroencephalograph (EEG), skin conductance level (SCL), and blood volume pulse (BVP) were monitored during prebaseline, meditation, and postbaseline periods. Visual analyses of the data showed a decrease in respiration rate during the meditation from a mean of 11 breaths/min for the pre-and 13 breaths/min for the postbaseline to a mean of 5 breaths/min during the meditation, with a predominance of abdominal/diaphragmatic breathing. There was also more alpha EEG activity during the meditation (M D 1.71 ¹V) compared to the pre-(M D .47 ¹V) and postbaseline (M D .78 ¹V) periods, and an increase in theta EEG activity immediately following the meditation (M D .62 ¹V) compared to the pre-baseline and meditative periods (each with M D .26 ¹V). These findings suggest that a shift in breathing patterns may contribute to the development of alpha EEG, and those patterns need to be investigated further.
KEYWORDS: meditation; EEG; alpha; respiration; breathing.
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Discussion:
The decrease in respiration from 11 (prebaseline) and 13 (postbaseline) to 5 breaths/min, with continued slow breathing at 5 breaths/min during the meditation period, demonstrates significant meditative control and experience by this Yogi. It suggests a decrease in arousal that appears consistent with other findings on the physiological correlates of meditation that show a decrease in respiration. Although previous studies have reported a decrease in breathing rate, the pattern of breathing is not usually noted. In this subject there was a consistent increase in abdominal over thoracic breathing seen during the meditation period. Abdominal/diaphragmatic breathing seems to be an integral part of many relaxation techniques. Because of this, aclose rexamination of abdominal breathing patterns of well-trained practitioners of meditation may reveal important findings. Researchers may discover, for example, that breathing plays a much more pivotal role in acquiring and maintaining a meditative state than previously thought.
There appears to be a significant increase in alpha wave production by the Yogi when he entered his meditative state, which was closely associated with the slower abdominal breathing discussed above. This production of alpha EEG is consistent with many other f indings on the physiological correlates of meditation and yoga (Anad et al., 1961; Corby et al., 1978; Delmonte, 1984a; Dostalek et al., 1979; Kamatsu et al., 1957; Woolfolk, 1975). However, none have discussed the possible influence of respiration on alpha EEG production. The correlation between deep, slow, abdominal breathing and alpha EEG production suggests that this type of breathing pattern may contribute to the increase in alpha EEG as proposed by Fried (1987). A measure of metabolic rate and PCO2 may help further our understanding of physiological processes during meditation. These findings further suggest that respiration may play an integral role in acquiring and maintaining a meditative state.
An increase in theta activity immediately following the meditation also seemed apparent in this case study. Although there are studies reporting some theta activity during meditation (Corbyetal., 1978; Herbert &Lehmann,1977;Jevningetal.,1992),thereareno studies reporting on this kind of activity following a period of meditation. Because theta can be associated with pleasure, it is not surprising that it was recorded following an activity for which the subject has many years experience. One would expect an individual to continue practicing meditation for such a long period of time only if it were enjoyable to him or her.
Manyof the findings here are similar to those in previous reports on the physiological correlates of meditation and yoga (Jevning et al., 1992; Morse et al., 1984; Delmonte, 1984a; Woolfolk, 1975). The uniqueness of this investigation is in the level and expertise of the subject that was studied. Examining such individuals may help to better identify the physiological correlates, and benefits of the exercise by revealing development that takes place only after achieving a high level of proficiency. This may help explain the contradictory findings surrounding the physiological correlates of meditation by creating a more accurate and complete picture of physiology during meditative practices.
Although respiration patterns have often been associated with meditation, few studies report  on this data. The finding that a subject can breathe continuously at about 5 breaths/min without experiencing any air hunger or excessive arousal, with a concurrent increase in occipital alpha EEG activity, demonstrates the meditative skills of the subject. Breathing may also be one of the physiological mechanisms by which the meditation experience can easily be integrated and anchored into daily life. By refocusing on breathing during the day, the meditative state may be reestablished. Further studies comparing advanced practitioners of yoga to those who are less proficient would be desirable, as would research on larger groups of expert practitioners so that meaningful statistical analyses could be done.
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FOR DETAILS AND RELATED RESEARCH FOLLOW THE LINK:
 
Jiří Kroc
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Mark Alber, Adrian Buganza Tepole, William R. Cannon, Suvranu De, Salvador Dura-Bernal, Krishna Garikipati, George Karniadakis, William W. Lytton, Paris Perdikaris, Linda Petzold and Ellen Kuhl
Abstract:
Fueled by breakthrough technology developments, the biological, biomedical, and behavioral sciences are now collecting more data than ever before. There is a critical need for time-and cost-efficient strategies to analyze and interpret these data to advance humanhealth. The recent rise of machine learning as a powerful technique to integrate multimodality, multifidelity data, and reveal correlations between intertwined phenomena presents a special opportunity in this regard. However, machine learning alone ignores the fundamental laws of physics and can result in ill-posed problems or non-physical solutions. Multiscale modeling is a successful strategy to integrate multiscale, multiphysics data and uncover mechanisms that explain the emergence of function. However, multiscale modeling alone often fails to efficiently combine large datasets from different sources and different levels of resolution. Here we demonstrate that machine learning and multiscale modeling can naturally complement each other to create robust predictive models that integrate the underlying physics to manage ill-posed problems and explore massive design spaces. Wereview the current literature, highlight applications and opportunities, address open questions, and discuss potential challenges and limitations in four overarching topical areas: ordinary differential equations, partial differential equations, data-driven approaches, and theory-driven approaches. Towards these goals, we leverage expertise in applied mathematics, computer science, computational biology, biophysics, biomechanics, engineering mechanics, experimentation, and medicine. Our multidisciplinary perspective suggests that integrating machine learning and multiscale modeling can provide new insights into disease mechanisms, help identify new targets and treatment strategies, and inform decision making for the benefit of human health.
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CONCLUSIONS
Machine learning and multiscale modeling naturally complement and mutually benefit from one another. Machine learning can explore massive design spaces to identify correlations and multiscale modeling can predict system dynamics to identify causality. Recent trends suggest that integrating machine learning and multiscale modeling could become key to better understand biological, biomedical, and behavioral systems. Along those lines, we have identified five major challenges in moving the field forward.
The first challenge is to create robust predictive mechanistic models when dealing with sparse data. The lack of sufficient data is a common problem in modeling biological, biomedical, and behavioral systems. For example, it can result from an inadequateexperimental resolution or an incomplete medical history. A critical first step is to systematically identify the missing information. Experimentally, this can guide the judicious acquisition of new data or even the design of new experiments to complement the knowledge base. Computationally, this can motivate supplementing the available training data by performing computational simulations. Ultimately, the challenge is to maximize information gain and optimize efficiency by combining low-and highresolution data and integrating data from different sources, which, in machine learning terms, introduces a multifidelity, multimodality approach.
The second challenge is to manage ill-posed problems. Unfortunately, ill-posed problems are relatively common in the biological, biomedical, and behavioral sciences and can result from inverse modeling, for example, when identifying parameter values or identifying system dynamics. A potential solution is to combine deterministic and stochastic models. Coupling the deterministic equations of classical physics—the balance of mass, momentum, and energy—with the stochastic equations of living systems—cell-signaling networks or reaction-diffusion equations —could help guide the design of computational models for problems that are otherwise ill-posed. Along those lines, physicsinformed neural networks and physics-informed deep learning are promising approaches that inherently use constrained parameter spaces and constrained design spaces to manage ill-posed problems. Beyond improving and combining existing techniques, we could even think of developing entirely novel architectures and new algorithms to understand ill-posed biological problems inspired by biological learning.
The third challenge is to efficiently explore massive design spaces to identify correlations. With the rapid developments in gene sequencing and wearable electronics, the personalized biomedical data has become as accessible and inexpensive as never before. However, efficiently analyzing big datasets within massive design spaces remains a logistic and computational challenge. Multiscale modeling allows us to integrate physicsbased knowledge to bridge the scales and efficiently pass information across temporal and spatial scales. Machine learning can utilize these insights for efficient model reduction towards creating surrogate models that drastically reduce the underlying parameter space. Ultimately, the efficient analytics of big data, ideally in real time, is a challenging step towards bringing artificial intelligence solutions into the clinic.
The fourth challenge is to robustly predict system dynamics to identify causality. Indeed, this is the actual driving force behind integrating machine learning and multiscale modeling for biological, biomedical, and behavioral systems. Can we eventually utilize our models to identify relevant biological features and explore their interaction in real time? A very practical example of immediate translational value is whether we can identify disease progression biomarkers and elucidate mechanisms from massive datasets, for example, early biomarkers of neurodegenerative disease, by exploiting the fundamental laws of physics. On a more abstract level, the ultimate challenge is to advance data-and theory-driven approaches to create a mechanistic understanding of the emergence of biological function to explain phenomena at higher scale as a result of the collective action on lower scales.
The fifth challenge is to know the limitations of machine learning and multiscale modeling. Important steps in this direction are analyzing sensitivity and quantifying of uncertainty. While machine learning tools are increasingly used to perform sensitivity analysis and uncertainty quantification for biological systems, they are at a high risk of overfitting and generating non-physical predictions. Ultimately, our approaches can only be as good as the underlying models and the data they have been trained on, and we have to be aware of model limitations and data bias. Preventing overfitting, minimizing data bias, and increasing rigor and reproducibility have been and will always remain the major challenges in creating predictive models for biological, biomedical, and behavioral systems.
Please, find m9re at the following link:
 
Johannes W. Dietrich
added a research item
Is data-driven analysis sufficient for understanding the COVID-19 pandemic and for justifying public health regulations? In this paper, we argue that such analysis is insufficient. Rather what is needed is the identification and implementation of over-arching hypothesis-related and/or theory-based rationales to conduct effective SARS-CoV2/COVID-19 (Corona) research. To that end, we analyse and compare several published recommendations for conceptual and methodological frameworks in medical research (e.g., public health, preventive medicine and health promotion) to current research approaches in medical Corona research. Although there were several efforts published in the literature to develop integrative conceptual frameworks before the COVID-19 pandemic, such as social ecology for public health issues and systems thinking in health care, only a few attempts to utilize these concepts can be found in medical Corona research. For this reason, we propose nested and integrative systemic modelling approaches to understand Corona pandemic and Corona pathology. We conclude that institutional efforts for knowledge integration and systemic thinking, but also for integrated science, are urgently needed to avoid or mitigate future pandemics and to resolve infection pathology.
Jiří Kroc
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Francesca Borgo, Alessandra Riva Sara Bertelli, Stefania Garbossa E. Pontiroli, Giulia Morace, Alberto Benetti, Maria Cristina Casiraghi, Simona Anselmetti, Silvio Scarone, Antonio & Elisa Borghi
PLoS ONE 12:6 (2017)
DOI: 10.1371/journal.pone.0179739
Abstract:
Anorexia nervosa (AN) is a psychiatric disease with devastating physical consequences, with a pathophysiological mechanism still to be elucidated. Metagenomic studies on anorexia nervosa have revealed profound gut microbiome perturbations as a possible environmental factor involved in the disease. In this study we performed a comprehensive analysis integrating data on gut microbiota with clinical, anthropometric and psychological traits to gain new insight in the pathophysiology of AN. Fifteen AN women were compared with fifteen age-, sex-and ethnicity-matched healthy controls. AN diet was characterized by a significant lower energy intake, but macronutrient analysis highlighted a restriction only in fats and carbohydrates consumption. Next generation sequencing showed that AN intestinal microbiota was significantly affected at every taxonomic level, showing a significant increase of Enterobacteriaceae, and of the archeon Methanobrevibacter smithii compared with healthy controls. Onthecontrary, the genera Roseburia, Ruminococcus and Clostridium, were depleted, in line with the observed reduction in AN of total short chain fatty acids, butyrate, and propionate. Butyrate concentrations inversely correlated with anxiety levels, whereas propionate directly correlated with insulin levels and with the relative abundance of Roseburia inulinivorans, a knownpropionate producer. BMI represented the best predictive value for gut dysbiosis and metabolic alterations, showing a negative correlation with Bacteroides uniformis (microbiota), with alanine aminotransferase (liver function), and with psychopathological scores (obsession-compulsion, anxiety, and depression), and a positive correlation with white blood cells count. In conclusion, our findings corroborate the hypothesis that the gut dysbiosis could take part in the AN neurobiology, in particular in sustaining the persistence of alterations that eventually result in relapses after renourishment and psychological therapy, but causality still needs to be proven.
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Discussion:
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Changes in the abundance of microbial communities lead to changes in the quantity/quality of microbial metabolites. Indeed, reduction in Firmicutes is in line with the lower fecal butyrate concentration in AN group. Interestingly, butyrate was negatively correlated with depression and anxiety. Sodium butyrate has been demonstrated to elicit antidepressant effects on murine brain. When injected systemically, sodium butyrate induced a short-lasting, transient acetylation of histones in frontal cortex and hippocampus, in conjunction with dynamic changes in expression of brain-derived neurotrophic factor (BDNF), thereby resulting in an antidepressant-like behavioral response [55].
Faecal propionate was also significantly reduced in AN subjects. A depletion in Roseburia species, and in particular of Roseburia inulinivorans, could result in a decrease production of propionate [56]. R. inulinivorans produces propionate from fucose via propanediol, and butyrate when grown in the presence of glucose [57]. Interestingly, our data showed a significant direct correlation between this species and insulin concentration, and insulin levels in AN group were significantly lower than healthy controls. This “profile” suggests a possible link between Roseburia species and insulin metabolism. A reduced insulin is a phenomenon well documented in literature [58] that helps AN subjects to preserve euglycemia.
Propionate has beneficial effects on β-cell function, potentiating glucose-stimulated insulin release and maintaining β-cell mass through inhibition of apoptosis [59]. On the other hand, propionate has been shown to inhibit adipogenesis [60], and the link might be represented by reduced insulin levels.
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Anorexic patients, as expected, showed reduced BMI, fat mass, and free fat mass if compared with healthy subjects. BMI is considered a severity index in AN patients, especially to define enduring AN [62]. Despite nutritional and psychological support, all enrolled subjects failed to recover BMI or stabilize weight gain, leading to a fluctuation in BMI as previously reported [63].
BMI resulted a good predictive value for dysbiosis level. The correlation analysis revealed that Bacteroides uniformis was negatively correlated with BMI, in agreement with our recent study on obese children in which members of the Bacteroidetes phylum were generally good predictors of BMI [20].
BMI was also inversely correlated with all psychological tests, and in particular with obsession-compulsion, depression, and anxiety. Longitudinal studies on AN cohorts suggested that weight gain during renourishment, leads to improvements of psychological symptoms [6].
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Jiří Kroc
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Anna Jaśkiewicz, Beata Pająk, Anna Litwiniuk, Kaja Urbańska & Arkadiusz Orzechowski
Oxidative Medicine and Cellular Longevity 2018(11):1-22
DOI: 10.1155/2018/6463807
Abstract:
The present study investigated the cytotoxic effects of statins (atorvastatin (ATR) and simvastatin (SIM), resp.) and methyl-betacyclodextrin (MβCD), at their respective IC50 concentrations, on muscle regeneration in the in vitro model of murine C2C12 myoblasts. Cotreatment with mevalonate (MEV), farnesol (FOH), geranylgeraniol (GGOH), or water-soluble cholesterol (Chol-PEG) was employed to determine whether the statin-dependent myotoxicity resulted from the lower cholesterol levels or the attenuated synthesis of intermediates of mevalonate pathway. Our findings demonstrated that while GGOH fully reverted the statin-mediated cell viability in proliferating myoblasts, Chol-PEG exclusively rescued MβCD-induced toxicity in myocytes. Statins caused loss of prenylated RAP1, whereas the GGOH-dependent positive effect was accompanied by loss of nonprenylated RAP1. Geranylgeranyltransferases are essential for muscle cell survival as inhibition with GGTI-286 could not be reversed by GGOH cotreatment. The increase in cell viability correlated with elevated AKT 1(S463) and GSK-3β(S9) phosphorylations. Slight increase in the levels of autophagy markers (Beclin 1, MAP LC-3IIb) was found in response to GGOH cotreatment. Autophagy rose time-dependently during myogenesis and was inhibited by statins and MβCD. Statins and MβCD also suppressed myogenesis and neither nonsterol isoprenoids nor Chol-PEG could reverse this effect. These results point to GGOH as the principal target of statin-dependent myotoxicity, whereas plasma membrane cholesterol deposit is ultimately essential to restore viability of MβCD-treated myocytes. Overall, this study unveils for the first time a link found between the GGOH-and Chol-PEG-dependent reversal of statin-or MβCD-mediated myotoxicity and cytoprotective autophagy, respectively.
Introduction:
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There is evidence that statin-induced muscle toxicity is associated with inhibition of protein geranylgeranylation [16]. Prenylation with nonsterol isoprenoids is an essential step in activating certain small GTPases including RAP. This reactionissolelydependentongeranylgeranylationofRAP1A catalysed in skeletal muscle by prenyltransferases including protein geranylgeranyltransferase type I, EC 2.5.1.59, and protein geranylgeranyltransferase type II, EC 2.5.1.60 [17]. Skeletal muscle growth and regeneration (myogenesis) take place in two subsequent phases. After an initial stage of cell proliferation, myoblasts withdraw from the cell cycle and differentiate and fuse to form multinucleated myotubes and muscle fibers [18, 19]. The exact role of RAP1A in each one of these steps is not known, although some studies conducted with RAP1A overexpressing muscle cells indicate that while GTP-bound RAP1A inhibits myogenic differentiation, the GDP-bound protein favors the formation of myotubes [20]. Previous studies from the same group also indicate that RAP1A may regulate the structural organization of late endosomes and lysosomes and therefore influence intracellular degradative pathways [21]. In this sense, GDP-bound RAP1A clustered with acidic structures in the perinuclear region of the myoblasts where the lysosomal proteolytic enzymes likely play an important role during myogenic differentiation [22]. Current research also points out to autophagy as an important tool supporting the intracellular reorganization processes needed for conversion of myoblasts to myotubes [23].
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Conclusions:
Myotoxicity induced by ATR and SIM is associated with the reduced GGOH-dependent prenylation of RAP1 protein. (2) Lower myotoxicity is reflected by the respective increase in AKT 1 (S463) and GSK-3β (S9) phosphorylation. (3) Geranylgeranyltransferases (GGTs) control myocyte viability through GGOH, which in excess is likely myotoxic. (4) Cytoprotective autophagy is elevated in myocytes during myogenesis. MEV, GGOH, and Chol-PEG are able to reverse statin-or MβCD-impaired autophagy. (5) Plasma membrane cholesterol is fundamental for the survival of MβCD-challenged myocytes. (6) Muscle differentiation is impaired by statins or MβCD, and nonsterol isoprenoids or Chol-PEG could not reverse this effect.
 
Oleksandr P. Romanchuk
added a research item
The aim of this study was to determine the changes in the cardiorespiratory system activity under the influence of traction manipulations in the thoracic spine. The study involved 26 adults, including 18 women aged 39.6 ± 12.1 years and 8 men aged 36.3 ± 8.3 years. The mean age of patients was 38.6 ± 11.2 years. The work used an integral method of studying the cardiorespiratory system-spiroarteriocardiorhythmography (SAKR). SACR registration was performed before and after traction manipulations in the thoracic spine directly in the procedure of manual therapy. The study of the immediate effect of traction manipulations of SMT in the thoracic spine on the cardiorespiratory system allowed establishing the main significant effects: decrease in HR (min-1) from 85.1 (77.1; 94.2) to 79.5 (69.8; 87.6), p=0.000, decrease in duration of QTC (s) from 0.419 (0.404; 0.434) to 0.413 (0.401; 0.427), p=0.012, decrease in CO (dm 3) from 5.2 (4.6; 5.8) to 4.9 (4.4; 5.6), p=0.000, SI (dm 3 /m 2) from 3.05 (2.75; 3.30) to 2.90 (2.62; 3.20), p=0.000, increase in Vexp (L/s) from 0.28 (0.22; 0.34) to 0.31 (0.25; 0.39), p=0.030. The obtained data suggest that the main effects of traction manipulations on the thoracic spine are associated more with the changes in hemodynamic parameters of blood circulation due to activation of expiratory muscles and chest mobility, when the suction mechanisms of the chest and cardiovascular function of diaphragm are activated.
Jiří Kroc
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Mattias Desmet
Book, Chelsea Green Publishing (2022) 256 pages
ISBN 1645021726 (ISBN13: 9781645021728)
The world is in the grips of mass formation—a dangerous, collective type of hypnosis—as we bear witness to loneliness, free-floating anxiety, and fear giving way to censorship, loss of privacy, and surrendered freedoms. It is all spurred by a singular, focused crisis narrative that forbids dissident views and relies on destructive groupthink.
Desmet’s work on mass formation theory was brought to the world’s attention on The Joe Rogan Experience and in major alternative news outlets around the globe. Read this book to get beyond the sound bites!
Totalitarianism is not a coincidence and does not form in a vacuum. It arises from a collective psychosis that has followed a predictable script throughout history, its formation gaining strength and speed with each generation—from the Jacobins to the Nazis and Stalinists—as technology advances. Governments, mass media, and other mechanized forces use fear, loneliness, and isolation to demoralize populations and exert control, persuading large groups of people to act against their own interests, always with destructive results.
In The Psychology of Totalitarianism, world-renowned Professor of Clinical Psychology Mattias Desmet deconstructs the societal conditions that allow this collective psychosis to take hold. By looking at our current situation and identifying the phenomenon of “mass formation”—a type of collective hypnosis—he clearly illustrates how close we are to surrendering to totalitarian regimes.
With detailed analyses, examples, and results from years of research, Desmet lays out the steps that lead toward mass formation, including:
• An overall sense of loneliness and lack of social connections and bonds
• A lack of meaning—unsatisfying “bullsh*t jobs” that don’t offer purpose
• Free-floating anxiety and discontent that arise from loneliness and lack of meaning
• Manifestation of frustration and aggression from anxiety
• Emergence of a consistent narrative from government officials, mass media, etc., that exploits and channels frustration and anxiety 
 
In addition to clear psychological analysis—and building on Hannah Arendt’s essential work on totalitarianism, The Origins of Totalitarianism—Desmet offers a sharp critique of the cultural “groupthink” that existed prior to the pandemic and advanced during the COVID crisis. He cautions against the dangers of our current societal landscape, media consumption, and reliance on manipulative technologies and then offers simple solutions—both individual and collective—to prevent the willing sacrifice of our freedoms.
“We can honor the right to freedom of expression and the right to self-determination without feeling threatened by each other,” Desmet writes. “But there is a point where we must stop losing ourselves in the crowd to experience meaning and connection. That is the point where the winter of totalitarianism gives way to a spring of life.”
"Desmet has an . . . important take on everything that’s happening in the world right now."—Aubrey Marcus, podcast host
"[Desmet] is waking a lot of people up to the dangerous place we are now with a brilliant distillation of how we ended up here."—Robert F. Kennedy, Jr.
"One of the most important books I’ve ever read."—Ivor Cummins, The Fat Emperor Podcast
 
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Sanjeev Rastogi & Preeti Pandey
SCIENCE INDIA (May 2022) 27-31
Abstract:
The power of prayer has been known to ancient civilisations like India for long; it’s efficacy in aiding recovery from illness is now being increasingly
acknowledged by medical practitioners
From the text:
While initiating the prayer session every time, the one who is taking the for any real meaning initially, the process, when continued for some consecutive sessions, was able to show visible changes in the level of involvement of the whole team in the healing process. The team including the authors of this write-up has observed a higher energy state, less fatigability and better focus upon the objectives throughout the out-patient day unaffected by the increasing number of patients visiting the centre. After initiating the prayer sessions, the energy level of team members remained stable throughout the day without any feeling of exhaustion after finishing the job on any particular day. Inspired by the observations, the centre decided to continue this prayer practice as part of its working routine and culture.
As we have learned that prayer, no matter in what form it is done,
makes changes in the brain activities which eventually increase the feeling of worth among the individuals, doing prayer with OM albeit may have some additional advantages. OM chanting is found effective in improving pulmonary functions on most parameters in healthy individuals. OM chanting is also shown to reduce the sympathetic activities reflected by a significant decrease in the heart rate leading to a reduction in perceived stress.     
Spiritual practice, such as prayer or meditation, are associated with focusing attention on internal states. Structural magnetic resonance imaging (MRI) studies have revealed that individuals frequently involved in prayer show improved Neurofeedback (NF) performance compared to individuals who are not. It is suggested that due to the regular practice, the prayer practitioners become more skilful in gating incoming information provided by the NF system and avoiding task-irrelevant thoughts. Eventually this results in more focused visualisation of a task.   
To summarise, prayer and all other forms of spiritual healing have a substance based upon experiences, observations and preliminary scientific evidence. Such practices should therefore be experimented to a greater scale for finding their translational possibility in health care.
 
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Editor: Chukwuebuka Egbuna
Volume 2, Elsevier  2022
ISBN: 978-0-323-95574-4
Publisher's Synopsis
Coronavirus Drug Discovery, Volume Two: Antiviral Agents from Natural Products and Nanotechnological Applications presents detailed information on drug discovery against COVID-19. Sections in this volume present chapters that focus on the various antiviral agents from natural products that have the propensity to be used as chemical scaffolds for the development of drugs against COVID-19. Also captured are the dietary sources of antioxidant bioactives that may help boost the immune system for the management of COVID-19. Other chapters describe the application of nanotechnology for efficient and effective delivery of drugs against COVID-19.
Written by global team of experts, this book is an excellent resource for drug developers, medicinal chemists, pharmaceutical companies in R&D and research institutes in both academia and industry.
 
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Simona Ugrayová, Peter Švec, Ivan Hric , Sára Šardzíková, Libuša Kubáňová, Adela Penesová, Jaroslava Adamčáková, Petra Pačesová, Júlia Horáková, Alexandra Kolenová, Katarína Šoltys, Martin Kolisek & Viktor Bielik
Biology 11:5 (2022) 785
DOI: 10.3390/biology11050785
Simple Summary: Gut microbiome research has rapidly advanced with good perspectives for the diagnostics and/or therapy of a plethora of diseases, including metabolic and neurodegenerative diseases and various types of cancer. In this study, we examined the composition of the fecal microbiota of eligible children with acute lymphoblastic leukemia (ALL) after hematopoietic stem cell transplantation (HSCT). We found a negative effect of HSCT treatment on microbiome bacteAcademic Editors: Ger Rijkers, Fengqin Feng and Hao Zhong Received: 14 April 2022 Accepted: 19 May 2022 Published: 21 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). rial diversity and richness with microbial monodominance by pathogenic bacteria in pediatric ALLpatients after 3 months. The changes in the gut microbiota were associated with systemic inflammation on day + 28. However, promisingly, we have observed an association between bacterial diversity and physical exercise during HSCT treatment. Our findings provide additional support for the importance of investigating the gut microbiome in children with cancer.
Abstract: Gut microbiome impairment is a serious side effect of cancer treatment. The aim of this study was to identify the effects of hematopoietic stem cell transplantation (HSCT) treatment on gut microbiota composition in children with acute lymphoblastic leukemia (ALL). Fecal microbiotas were categorized using specific primers targeting the V1–V3 region of 16S rDNA in eligible pediatric ALLpatients after HSCT (n = 16) and in healthy controls (Ctrl, n = 13). An intra-hospital exercise program was also organized for child patients during HSCT treatment. Significant differences in gut microbiota composition were observed between ALL HSCT and Ctrl with further negative effects. Plasma C-reactive protein correlated positively with the pathogenic bacteria Enterococcus spp. and negatively with beneficial bacteria Butyriccocus spp. or Akkermansia spp., respectively (rs = 0.511, p =0.05; rs = −0.541, p = 0.04; rs = −0.738, p = 0.02). Bacterial alpha diversity correlated with the exercise training characteristics. Therefore, specific changes in the microbiota of children were associated with systemic inflammation or the ability to exercise physically during HSCT treatment.
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Introduction:
...
Promising fitness and overall health benefits have been reported, even after a relatively short-term intra-hospital exercise training program in pediatric patients after bone marrow transplantation [16]. Unfortunately, most of the positive effects resulting from regular physical activity during cancer treatment are documented primarily in adult patients [17]. Therefore, another aim of this pilot study has been to find an association between intrahospital physical exercises completed by children after HSCT and the structure of their microbiota. Our intention has been to create a structured exercise program carried out within a relatively small hospital transplant room (transplant box) with limited exercise equipment and strict hygienic precautions. Since enteral nutrition has been shown to be more effective in promoting intestinal microbial homeostasis compared with parenteral nutrition [18], our study has also focused on finding an association between gut microbiome and supportive nutritional treatment.
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Conclusions:
This study has established the negative effect of cancer treatment on bacterial diversity and richness in pediatric HSCT patients. The relative abundance of beneficial bacteria decreases from day + 0 to day + 90 after HSCT. Furthermore, we report a shift in the gut microbiome composition, with a microbial monodominance by unclassified Enterococcus species (spp.) and family Enterococcaceae during the 3 months after HSCT. These specific changes in the microbiota are associated with systemic inflammation on day + 28. However, promisingly, in this pilot study, we have observed an association between alpha bacterial diversity and training variables during HSCT treatment. We assume that the pediatric patients exhibiting a better clinical condition and more favorable gut microbiome can exercise more. Further research is required to confirm whether intervention involving physical exercise influences clinical outcomes through effects on the gut microbiota.
 
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Amrit Pal Kaur, Sonali Bhardwaj, Daljeet Singh Dhanjal, Eugenie Nepovimova, Natália Cruz-Martins, Kamil Kuča, Chirag Chopra, Reena Singh, Harsh Kumar, Fatih Şen, Vinod Kumar, Rachna Verma & Dinesh Kumar
Biomolecules 11 (2021) 440
DOI: 10.3390/biom11030440
Abstract:
Prebiotics are either natural or synthetic non-digestible (non-)carbohydrate substances that boost the proliferation of gut microbes. Undigested fructooligosaccharides in the large intestine are utilised by the beneficial microorganisms for the synthesis of short-chain fatty acids for their own growth. Although various food products are now recognized as having prebiotic properties, several others, such as almonds, artichoke, barley, chia seeds, chicory, dandelion greens, f laxseeds, garlic, and oats, are being explored and used as functional foods. Considering the benefits of these prebiotics in mineral absorption, metabolite production, gut microbiota modulation, and in various diseases such as diabetes, allergy, metabolic disorders, and necrotising enterocolitis, increasing attention has been focused on their applications in both food and pharmaceutical industries, although some of these food products are actually used as food supplements. This review aims to highlight the potential and need of these prebiotics in the diet and also discusses data related to the distinct types, sources, modes of action, and health benefits. Keywords:prebiotics; dietary fiber; oligosaccharides; non-digestible carbohydrates; short-chain fatty acids
Discussion:
6.2. Effect of Prebiotics on Metabolite Production Direct and indirect fermentation of specific compounds generates primary and secondary metabolites, which show health benefits in humans [199]. Microbes present in the gut synthesize SCFAs via fermentation of carbohydrates, amino acids, and other nutrients that are not absorbed in the small intestine [200]. Acetate, butyrate, and propionate are SCFAs that are synthesized after primary anaerobic fermentation of prebiotics by enteric microbes [201]. These SCFAs play a key role as a substrate for cholesterol, glucose, and lipid metabolism. Acetate and propionate act as substrates for peripheral tissues [202]; butyrate plays a vital role as a primary nutrient for colonocytes and serves as a histone deacetylase inhibitor. In addition, as they have ability to inhibit the NF-κB signalling pathway in colonocytes; they contribute to reduce the levels of intestinal inflammation markers and maintain the barrier integrity [203,204]. Other than this, acetate, butyrate, and propionate also boost the G-protein-coupled receptors (GPRs) that modulate the essential metabolic hormones, including GLP-1 and peptide YY (PYY) [205]. Even though SCFAproduction has numerous positive outcomes, there is a need for extensive research to uncover the real potential [206,207].
6.3. Effect of Prebiotics on Mineral Absorption
The primary target of prebiotic consumption is to increase the absorption and bioavailability of calcium to make bones healthy in infants and the elderly[207]. Worldwide,the consumption of prebiotics has reduced the risk of bone fractures and osteoporosis [208]. Calcium is primarily absorbed in the distal intestine, which is stimulated by acidic fermentation of prebiotic dietary fibers as well as chemical changes by numerous microbes [209], although clinical evaluations related to mineral absorption in association with prebiotics have provided mixed results [210]. Few studies related to oligofructose, GOS, inulin, and FOS consumption have shown no significant changes in calcium absorption [211], whereas some studies involving oligosaccharide components with lactulose have shown a significant increase in calcium absorption [212].
6.5. Effect of Prebiotics on Diabetes
Diabetes is a complex disease occurring via the interaction between environmental, epigenetic, and genetic factors [218]. Prebiotics play an integral role in the regulation of genes and dramatically impact metabolic functions [219]. Various dietary fibers and carbohydrates generate a link between polymorphisms, which inactivates the insulin-resistant genes [220]. A study conducted on human gut microflora unveiled the interrelation of type 2 diabetes and gut microbiota [221]. Other studies claim the rise inflammatory stress is the cause for the onset of diabetes. Indeed, the daily nutritional diet is believed to be a key factor in the management of diabetes [222]. Studies have suggested that an appropriate diet can significantly decrease the postprandial glucose response [223]. In this way, food items, such as cereals, fruits, spices, and legumes, contain active ingredients such as polyphenols and dietary fibers that aid in decreasing the glycemic index and insulin immune response in patients with diabetes [224]. However, the type of carbohydrates, dosage, and source determine their glucose-reducing effect [225]. For example, inulin-type fructans (ITF) are non-digestible carbohydrate prebiotics with the ability to regulate the growth and composition of gut microbes while confering positive health effects [225]. Arabinoxylan (AX), a prebiotic abundantly found in aleurone fractions and wheat bran, has been reported to undergo fermentation in the colon via beneficial microbes and to positively influence the hyperglycemic levels in diabetic patients [226]. A study conducted on a diabetic mouse model revealed that an increase in the probiotic count in the colon due to supplementation of AX improved insulin resistance [227]. Furthermore, extensive studies are being conducted to understand the impact of AX on gut microbes and to unveil the mechanism of action of AX in lowering diabetic complications [228].
Conclusions:
The acceptance of prebiotics as a dietary food ingredient has been found effective in nourishing the gut microbiota. The chemical structure of prebiotics is short-chain oligosaccharides that are fermented by the gut microbiota and enhance their growth. Incorporation of these prebiotics in the diet improves human health and prevents the onset of various diseases. Additionally, beneficial bacteria proliferate and inhibit pernicious bacterial growth and maintain the intestinal balance. They are obtained from various plant sources, but due to their high global demand, the production of such compounds at industrial scales is required. Nowadays, enzymes and microbes are used to increase the availability and variety of prebiotics, such as indigestible carbohydrates, instead of using these compounds in the food industries. Moreover, agro-industrial residues can also be used as alternative substrates for prebiotic production, such as XOS. Synthesized biotics are used to lower the cost of prebiotics on the market and also to improve their quality. In addition, these indigestible carbohydrates can be used as ingredients for preparing different food products, so that the final product has better sensorial and technological features. Nonetheless, to decipher the exact mechanisms behind the beneficial impact of prebiotics on humanhealth is challenging because this depends on the gut microbiota involved in indigestible carbohydrate fermentation that ultimately provides health-promoting functions. Another advantage of prebiotics is their texture-forming ability, which allows them to be used as replacements for fat or sugar because of their exceptional organoleptic quality. Thus, prebiotics can be used to produce various added-value food products due to their bifidogenic properties, ultimately enabling food industries to create new functional foods with unique ingredients, which will positively be accepted by consumers because of the associated health benefits. Also noteworthy is the symbiotic formulation, a different area in this field that remains unexplored. In this approach, a different combination of prebiotics and probiotics can be developed to vary the degree of the therapeutic effect. Thus, studies of these formulations at the nutrigenomics level should be performed to provide deep insights into the individual response to different nutrients.
 
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American Heart Association Basic Cardiovascular Sciences Meeting – Presentation: P3119
Research Highlights:
• Researchers have demonstrated for the first time a potential route of the SARS-CoV-2 spike protein damaging the heart.
• In study evaluating mice and human heart cells, the SARS-CoV-2 spike protein inflamed the heart muscle cells, which can lead to heart injury.
Embargoed until 8 a.m. CT/9 a.m. ET, Monday, July 25, 2022
CHICAGO, July 25, 2022 — Heart damage is common among patients hospitalized with COVID-19, leading many to wonder how the virus affects the heart. Now, researchers have found that the spike protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can lead to heart muscle injury through the inflammatory process, according to preliminary research to be presented at the American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions 2022. The meeting, held in Chicago on July 25-28, offers the latest research on basic and translational cardiovascular science.
Read more here:
 
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Caroline E. Childs, Henna Röytiö, Esa Alhoniemi, Agnes A. Fekete, Sofia D. Forssten, Natasa Hudjec, Ying Ni Lim, Cara J. Steger, Parveen Yaqoob, Kieran M. Tuohy, Robert A. Rastall, Arthur C. Ouwehand & Glenn R. Gibson
British Journal of Nutrition 111:11 (2014) 1945–1956
DOI: 10.1017/S0007114513004261
Abstract
Prebiotics, probiotics and synbiotics are dietary ingredients with the potential to influence health and mucosal and systemic immune function by altering the composition of the gut microbiota. In the present study, a candidate prebiotic (xylo-oligosaccharide, XOS, 8 g/d), probiotic (Bifidobacterium animalis subsp. lactis Bi-07, 109 colony-forming units (CFU)/d) or synbiotic (8 g XOS+109 CFU Bi-07/d) was given to healthy adults (25-65 years) for 21 d. The aim was to identify the effect of the supplements on bowel habits, self-reported mood, composition of the gut microbiota, blood lipid concentrations and immune function. XOS supplementation increased mean bowel movements per d (P= 0·009), but did not alter the symptoms of bloating, abdominal pain or flatulence or the incidence of any reported adverse events compared with maltodextrin supplementation. XOS supplementation significantly increased participant-reported vitality (P= 0·003) and happiness (P= 0·034). Lowest reported use of analgesics was observed during the XOS+Bi-07 supplementation period (P= 0·004). XOS supplementation significantly increased faecal bifidobacterial counts (P= 0·008) and fasting plasma HDL concentrations (P= 0·005). Bi-07 supplementation significantly increased faecal B. lactis content (P= 0·007), lowered lipopolysaccharide-stimulated IL-4 secretion in whole-blood cultures (P= 0·035) and salivary IgA content (P= 0·040) and increased IL-6 secretion (P= 0·009). XOS supplementation resulted in lower expression of CD16/56 on natural killer T cells (P= 0·027) and lower IL-10 secretion (P= 0·049), while XOS and Bi-07 supplementation reduced the expression of CD19 on B cells (XOS × Bi-07, P= 0·009). The present study demonstrates that XOS induce bifidogenesis, improve aspects of the plasma lipid profile and modulate the markers of immune function in healthy adults. The provision of XOS+Bi-07 as a synbiotic may confer further benefits due to the discrete effects of Bi-07 on the gut microbiota and markers of immune function.
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Discussion
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Volunteers who received the XOS supplement exhibited a significant increase in fasting plasma HDL concentrations, with an associated trend for a lower total cholesterol:HDLcholesterol ratio. Lower plasma HDL concentrations have been identified as a significant risk factor for coronary disease(42). The average 0·07mM increase in HDL concentrations observed in volunteers receiving the XOS supplement is modest, but a 0·1mM increase has been estimated to induce a 10% reduction in CHD risk(43). The proposed mechanisms for the influence of dietary probiotics and prebiotics on plasma lipid concentrations have been generated based on data obtained from in vitro studies and animal models. These include the effect of probiotic bacteria on bile acids, the ability of probiotics to bind to cholesterol, the influence of circulating SCFA on hepatic cholesterol synthesis, the role of prebiotics in the reduction of cholesterol absorption, and the effects of fermentable carbohydrates on gastric emptying rates(44,45).
...
This suggests that even a modest increase in daily sugar intake is sufficient to alter HDL-cholesterol concentrations.
...
The effects of both XOS and Bi-07 on the measures of immune status and function were observed. The effects that both probiotics and prebiotics can exert on immune function have been well described in a range of studies including in vitro assessment studies, animal models and human trials(26,46). Probiotics can exert indirect effects on immunity, via mechanisms including alteration of the composition of the gut microbiota, competitive inhibition of potential pathogen-binding sites and improvement of the gut barrier function(46). Probiotics also directly influence signalling pathways in intestinal epithelial cells and dendritic cells, with the potential to induce downstream effects on immune function(47). Prebiotics may influence immune function indirectly, by altering the composition of the gut microbiota or via their own direct effects, such as changes in pathogenassociated molecular patterns presented to the gut-associated lymphoid tissue(23).
...
XOS supplementation induced changes in the cell-surface markers on NKT cells and lowered IL-10 secretion. However, it cannot be excluded that the effects observed on NKT cells were in part influenced by the apparent increase in cell-surface marker expression during the MDX supplementation period. Bi-07 supplementation had significant effects on the systemic markers of immune function, leading to lower IL-4 secretion and salivary IgA content and higher IL-6 secretion. A XOS £ Bi-07 interaction altered B-cell-surface marker expression. IL-4 secretion is associated with Th2 inflammatory conditions such as asthma and hay fever and promotes B-cell differentiation(47). NKT cells are an important link between innate immunity and adaptive immunity. IL-6 and IL-10 are cytokines with proand anti-inflammatory actions, respectively, and the relative balance of these cytokines is important to prevent excessive inflammation. Salivary IgA is a marker of mucosal immunity, with its secretion being lowered during psychological and physical stress and lower levels being associated with an increased risk of urinary tract infections(48). Taken together, these effects suggest that XOS and Bi-07 have immunostimulatory effects, promoting Th1 responses and lowering Th2 activity. Therefore, these effects may be of benefit to individuals with suppressed Th1 activity, e.g. the elderly, or those with excessive Th2 activity, such as that occurring in atopic disease.
 
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Adele Costabile, Triana Bergillos-Meca, Pia Rasinkangas, Katri Korpela,  Willem M. de Vos  & Glenn R. Gibson
Frontiers in Immunology 8 (2017) 1443
DOI: 10.3389/fimmu.2017.01443
Abstract:
Background:  The aging process leads to a potential decline in immune function and adversely affects the gut microbiota. To date, many  in  vitro  and  in  vivo  studies focused on the application of synbiotics (prebiotics combined with probiotics) as a promising dietary  approach  to  affect  gut  microbiota  composition  and  improved  functioning  of  the immune system. However, studies using synbiotic preparations often have the limitation that it remains unclear whether any effect observed is a result of the prebiotic or probiotic or a synergistic effect of the combined supplement.
Objectives:  We investigated the effects of a probiotic  Lactobacillus rhamnosus  GG and pilus-deficient  L. rhamnosus  GG-PB12 combined with Promitor™  Soluble Corn Fiber (SCF, a candidate prebiotic) on fecal microbiota, metabolism, immunity, and blood lipids in  healthy  elderly  persons.  A  prospective,  double-blind,  placebo  controlled,  randomized, single-centered, crossover study in 40 healthy elderly subjects (aged 60–80  years) was carried out.  Volunteers were randomized to  consume either probiotic and prebiotic as synbiotic, prebiotic or placebo (maltodextrin) during 3  weeks. Three-week washout periods separated all the treatments. We assessed effects upon blood lipids, glucose, cytokines, natural killer (NK) cell activity, phenotype, and intestinal microbiota composition. SCF decreased IL-6, which was not observed with the synbiotics.
Results:  Consumption of  L. rhamnosus  GG combined with SCF increased NK  cell activity  compared  to  baseline  in  females  and  the  older  group.  In  the  fecal  microbiota analyses, the strongest community shifts were due to  L. rhamnosus  GG combined with SCF and SCF treatments.  L. rhamnosus  GG combined with SCF and  L. rhamnosus GG-PB12 combined with SCF significantly increased the genus  Parabacteroides. L. rhamnosus  GG combined with SCF and SCF increased concentrations of Ruminococcaceae Incertae Sedis.  Oscillospira  and  Desulfovibrio  slightly decreased in the  L. rhamnosus  GG combined with SCF group, whereas  Desulfovibrio  decreased also in the  L. rhamnosus  GG-PB12 combined with SCF group.  L. rhamnosus  GG combined with SCF reduced total cholesterol and LDL-cholesterol in volunteers with initially elevated concentrations. C-reactive protein significantly decreased during  L. rhamnosus GG-PB12 combined with SCF intervention compared to baseline.
Conclusion:  In conclusion, the synbiotic combination of  L. rhamnosus  GG with SCF showed a tendency to promote innate immunity by increasing NK  cell activity in elderly women and in 70 to 80-year-old volunteers and decreased TC and LDL-c in hypercholesterolemic  patients.  In  addition,  L.  rhamnosus  GG-PB12  combined  with  SCF demonstrated an increase in NK  cell activity compared to SCF alone in older volunteers.  We  also found significant  positive  effects  on  the  immune  response,  evidenced  by  a decrease of the pro-inflammatory cytokine IL-6. Therefore, dietary intervention with  L. rhamnosus  GG combined with SCF could be of importance in elderly as an attractive option for enhancement of both the microbial and immune systems.
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Conclusion:
We could conclude that  L.  rhamnosus  GG combined with SCF intervention could be useful in the primary intervention of hypercholesterolemia  and  may  lead  to  reductions  in  risk  factors for CVD. The observed reduction of TC and LDL-c by  L. rham nosus  GG combined with SCF and not  L.  rhamnosus  GG-PB12 is of interest and may have various mechanistic explanations. First,  L.  rhamnosus  GG showed a much higher mucus-binding capacity than  L.  rhamnosus  GG-PB12 (19). Hence,  L.  rhamnosus GG  is  expected  to  reside  in  close  proximity  to  intestinal  cells, allowing for increased interactions. Second, the increased persistence of  L.  rhamnosus  GG may also impact the extent of host interactions. Both of these explanations imply that  L.  rhamnosus GG has beneficial host signaling capacity that affects TC and LDL-c concentrations. Third,  L.  rhamnosus  GG has a differential effect on the total intestinal community and hence it cannot be excluded that the affected microbial community is involved in reduction  of  hypercholesteremia.  Whatever  the  exact mechanism would be, the observation that TC and LDL-c concentrations were only reduced  by an intervention with  L.  rhamnosus  GG and  not  L.  rhamnosus  GG-PB12, provided evidence that the mucus-binding pili may confer a health influence. In conclusion, the synbiotic containing  L.  rhamnosus  GG combined with SCF showed a tendency to promote innate immunity by increasing NK  cell activity in elderly women and in 70- to 80-year-old volunteers and decreased TC and LDL-c in hypercholesterolemic patients. In addition,  L.  rhamnosus  LGG-PB12 combined with SCF demonstrated an increase in NK  cell activity compared to SCF alone in older volunteers. We also found significant positive effects on the immune response, evidenced by a decrease of the pro-inflammatory cytokine IL-6. Therefore, dietary intervention with  L.  rhamnosus  GG combined with SCF could be of importance in elderly as an attractive option for enhancement of both the microbial and immune systems.
 
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Raymond Trevor Bradley, Rollin McCraty, Mike Atkinson, Dana Tomasino, Alane Daugherty & Lourdes Arguelles
Applied Psychophysiology and Biofeedback  35:4 (2010) 261-83
DOI 10.1007/s10484-010-9134-x
Abstract
This study investigated the effects of a novel, classroom-based emotion self-regulation program (TestEdge) on measures of test anxiety, socioemotional function, test performance, and heart rate variability (HRV) in high school students. The program teaches students how to self-generate a specific psychophysiological state— psychophysiological coherence—which has been shown to improve nervous system function, emotional stability, and cognitive performance. Implemented as part of a larger study investigating the population of tenth grade students in two California high schools (N = 980), the research reported here was conducted as a controlled pre-and postintervention laboratory experiment, using electrophysiological measures, on a random stratified sample of students from the intervention and control schools (N = 136). The Stroop color-word conflict test was used as the experiment’s stimulus to simulate the stress of taking a high-stakes test, while continuous HRV recordings were gathered. The postintervention electrophysiological results showed a pattern of improvement across all HRV measures, indicating that students who received the intervention program had learned how to better manage their emotions and to self-activate the psychophysiological coherence state under stressful conditions. Moreover, students with high test anxiety exhibited increased HRV and heart rhythm coherence even during a resting baseline condition (without conscious use of the program’s techniques), suggesting that they had internalized the benefits of the intervention. Consistent with these results, students exhibited reduced test anxiety and reduced negative affect after the intervention. Finally, there is suggestive evidence from a matched-pairs analysis that reduced test anxiety and increased psychophysiological coherence appear to be directly associated with improved test performance—a finding consistent with evidence from the larger study.
Keywords Test anxiety Emotion self-regulation Student stress Heart rate variability/HRV Coherence Psychophysiology Biofeedback
Summary and Conclusion
This investigation adopted a broadened approach to studying and addressing the problem of student test anxiety, and, in so doing, has provided new findings regarding the interactions between physiological processes, emotions, learning, and cognitive performance.
...
In line with other studies on the utility of HRV (Appelhans and Luecken 2006; McCraty et al. 2006; Tiller et al. 1996; Thayer et al. 2009; Segerstrom and Solberg Nes 2007), the HRV measurements used in this study demonstrate that students exposed to the TestEdge program had acquired the self-regulatory ability to shift, under the pressure of a testing situation, into an optimal psychophysiological state conducive to emotional stability, improved cognitive performance, and overall health. This result was associated with a significant reduction in mean test anxiety and negative affect—especially for those in the high test anxiety subgroup, and a marginally significant improvement in standardized test performance for a small matched-pair subsample of students. Perhaps even more notable, the physiological data revealed that the students with high test anxiety had instantiated a healthier, more adaptive baseline pattern of psychophysiological function: they exhibited increased HRV and heart rhythm coherence during the experiment even without conscious use of the emotion regulation tools. This is likely the result of the brain and body’s familiarization with the psychophysiological correlates of the coherence state which had occurred through the learning and use of the coherence-building techniques. When maintained, the expected long-term consequences of this systemic repatterning of psychophysiological activity are sustained improvements in nervous system function, increased stress resiliency, greater emotional stability and control, and improved cognitive performance (McCraty et al. 2006; Thayer et al. 2009).
 
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Xiaoyun Su & Bin Yao
Trends in Microbiology 30:4 (2022) 314-317
DOI: 10.1016/j.tim.2022.01.003
Abstract:
Orally administered enzymes can have profound effects on the composition of the gut microbiota and may serve as an appealing alternative modulating agent. We summarize the three ways through which enzymes can influence the gut microbiota and discuss the challenges in choosing the right enzyme to modulate the gut microbiota.
From the text:
Basically, enzymes can affect the gut microbiota in three ways (Figure 1). First, some enzymes can kill gut microbes. Lysozymes, lysozyme-like glycoside hydrolases, and bacterial phage lysinsdirectly degrade peptidoglycan, a major constituent of the bacterial cell wall.
...
Second, enzymes can stimulate gut microbial growth. In humans, approximately half the amount of xylan in food is degraded by gut-resident microbial xylanases into xylooligosaccharides, which support the growth of certain gut microbes (such as Bacteroides, Bifidobacterium,and Lactobacillus spp.).
...
Third, enzymes can affect the gut microbiota byinterfering with microbial networking. Quorum sensing (QS) is one way in which the microbial community networks. By sensing signaling molecules, the microbes synchronize togeneratebiofilmandexcrete toxic molecules. Removal of QS molecules (quorum quenching) by enzymes such as N-acylhomoserinelactonasecanmodulate the gut microbiota in goldfish, as demonstrated by elevating the abundance of Proteobacteria and diminishing the pathogenic Aeromonas hydrophila in the gut [7].
 
Jiří Kroc
added an update
MohammadFazil & Sadia Nikhat
Phytotherapy Research 35:4 (2021) 2317–2335
DOI: 10.1002/ptr.6949
Abstract:
The 20th and 21st centuries have witnessed epidemics and pandemics of various infectious agents. The development of effective antimicrobials in the 20th century has been complemented with the emergence of resistant and mutant strains. In this context, we present a comprehensive overview of the preventive measures described in Unani medicine during epidemics. Unani medicine is a traditional medicine system included in the Indian Systems of Medicine. Unani medicine has an extensive description of epidemic infections and preventive and therapeutic measures for the same. Certain factors like environment, season, and geographical location of a place are known to determine the extent of infections, and their escalation to epidemics. Maintenance of general health, immune-stimulation, and disinfecting of the environment are advised as protective measures, for which many drugs are prescribed. In the case of illness, specific antimicrobial drugs of natural origin are prescribed. Herein we discuss these measures in detail, along with the scientific evidences of anti-microbial, immunomodulatory, and health-protective actions of these drugs.
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Introduction:
...
Various forms of traditional and complementary medicines are practiced around the world. Like traditional Arab medicine (Saad, Azaizeh, & Said, 2005), traditional Chinese medicine, Ayurveda, Homeopathy, and Unani medicine, to name a few (Fazil & Nikhat, 2020). Many of the drugs used in these traditional medicines have scientifically proven anti-bacterial, anti-fungal (Zhang et al., 2013), and anti-viral effects, even against drug-resistant strains (Ma et al., 2015). Unani (pronounced Yunanī) is a traditional medicine system of Hellenistic origin, founded on Hippocratic principles. It was later systematized, organized, and developed by Arabian and Persian scholars during the medieval ages (500–1500 AD), hence also referred to as Greco-Arabian medicine and Persian medicine. In this period, significant developments were made in various areas of medical science by famous scholars such as Ibn Sina (Avicenna, 980–1035 AD), Zakariya Razi (Rhazes, 865–925 AD), Abul Qasim Zahrawi (Abulcasis, 930–1013 AD), Rabban Tabari (838–870 AD), and many others (Saad et al., 2005). Around the 12th century, it was introduced into the Indian subcontinent by the Mughal emperors. Indian scholars such as Azam Khan (1814–1902 AD) made improvisations in Unani medicine with the indigenous knowledge and recorded their works in treatises which are presently regarded as authentic citable sources among the researchers of Unani System of Medicine (USM) (Zargaran, Zarshenas, Borhani-Haghighi, & Mohagheghzadeh, 2014). At present, Unani medicine is recognized as a traditional medicine by World Health Organization (WHO, 2010), and is also a component of Indian Systems of Medicine (The National Commission for Indian System of Medicine, 2019).
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Selected from the text:
Terpenes and terpenoids have broad-spectrum inhibitory activity against several air-borne pathogens (Aldred, 2009; Ludwiczuk et al., 2017).
For instance, the antibacterial and antifungal activity of Cinnamomum camphora and Pistacia lentiscus is attributed to the presence of camphor (Bachrouch et al., 2010; Shalaby et al., 2016).
Diterpene esters present in Lens culinaris have anti-viral activity (Ganesan & Xu, 2017).
Trans-cinnamaldehyde has an antioxidant and anti-inflammatory activity (Da Silveira, Sá, Andrade, De Oliveira, & De Sousa, 2014).
Polyphenols exist in nearly 8,000 structural variants and are widely found in fruits, vegetables, legumes, tea, and wine. They have a wide range of biological activities such as antioxidant, anti-cancer, cardioprotective, and anti-aging.
Phenolics such as gallic acid, ellagic acid, punicalagin, quercetin present in many fruits like pomegranate, grapes, guava, apple, mango, etc. have anti-microbial activity.
Hydrolysable ellagitannins present in P. granatum have demonstrated effective anti-oxidant and anti-tumor activities in-vitro. The tannins are present in maximum amount in fruit juice (Orak, Yagar, & Isbilir, 2012). Tannins such as chebulagic acid, corilagin present in T. chebula have neuroprotective and anti-bacterial effect (Saxena et al., 2017).
Vinegar contains acetic acid (Figure 1h), oxalic acid, and benzoic acid which penetrate the bacterial cell wall and interfere with intracellular pH, thereby causing death.
Flavonoids such as taxifolin, catechin, apigenin in T. indica have demonstrated anti-inflammatory, nephroprotective, and anti-bacterial activity (Komakech et al., 2019; Ullah et al., 2014).
β-sitosterol (Figure 1k) present in P. granatum (Wu & Tian, 2017) is one of the most important phytosterols. It is a proven immunomodulatory, anti-oxidant, and has dose-dependent anti-cancer activity (Miras-Moreno et al., 2016).
Anthraquinones present in R. australe have demonstrated inhibitory activity against Helicobacter pylori, Herpes simplex virus (emodin) and Candida albicans (rhein) (Bartnik & Facey, 2017).
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Conclusions:
...
The science of Unani medicine encompasses age-old wisdom on the understanding of health and disease, hypotheses founded on rational ideas, and a legacy of health-promoting and protecting measures based on diligent observation and extensive experience; resulting in a holistic approach to health care which remains irrefutable to this day. In addition to general methods of hygiene and healthmaintenance, protection during epidemics rests on a three-pronged approach: purification of air, improvement of immunity, and specific antimicrobial drugs in case of illness. The use of air-purifying drugs is a particularly interesting concept, which employs aromatic drugs such as S. benzoides, S. album, rose water etc. Besides creating a pleasant atmosphere, it is now known that they also reduce air-borne pathogens. Immuno-modulation is understandably a very important aspect of prevention. Unani physicians have advised the use of citrus fruits, vinegar, saffron and other health protective drugs which also have hepato-protective and antioxidant effects. In addition, drugs such as G. glabra, honey, Ferula narthex etc. are prescribed for their antimicrobial effects. The drugs contain several bioactive compounds as already elaborated in the paper. The most important aspect of natural medicines is that every drug contains several active molecules, which provide multiple actions, often in synergism (Pandith et al., 2018). Due to multiple modes of action, natural drugs are also capable of overcoming antibiotic resistance (Kim et al., 2016). There are certain distinct qualities of USM which set it apart from rest of the medicine systems, and provide effective solutions to control infections and epidemics. First and foremost, the drugs utilized in health-protection, immune-modulation and prevention of infection are easily available common herbs, which promotes acceptability and availability even in under-privileged areas. Second, many of the drugs used for environmental purification for example, Sandalwood, Rose water etc. have a luxurious aroma, which promotes relaxation alongwith reducing microbes. Thirdly, most drugs have multiple modes of actions, and many have a hepato-protective or nephro-protective effect alongwith other benefits (Radha & Laxmipriya, 2015). This is extremely important, as weakness of vital organs often complicates an otherwise less-serious illness (G. Guo et al., 2020). Most importantly, the presence of several bioactive ingredients in the drugs, with proven activities, strongly advocates further exploration of their beneficial effects.
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Francis Ribeiro de Souza, Daisy Motta-Santos, Douglas dos Santos Soares, Juliana Beust de Lima, Gustavo Gonçalves Cardozo, Luciano Santos Pinto Guimarães, Carlos Eduardo Negrão & Marcelo Rodrigues dos Santos
Journal of Science and Medicine in Sport 24 (2021) 913–918
DOI: 10.1016/ j.jsams.2021.05.011
Abstract:
Objectives:  We  compared  physical  activity  levels before  the outbreak  and quarantine measures with COVID-19-associated  hospitalization  prevalence in  surviving  patients infected with SARS-CoV-2. Additionally, we investigated the association  of  physical  activity  levels  with  symptoms of  the disease, length of  hospital  stay, and  mechanical  ventilation.
Design:  Observational, cross-sectional.
Methods:  Between  June 2020 and August  2020, we  invited Brazilian survivors and fully  recovered patients infected with SARS-CoV-2 to respond to  an online questionnaire.  We  shared  the electronic link to the questionnaire on  the  internet.  We  collected data about  clinical  outcomes  (symptoms,  medications, 3 hospitalization,  and  length  of  hospital  stay)  and cofactors, such as age, sex, ethnicity, preexisting  diseases, socioeconomic and educational,  and physical  activity  levels using  the International  Physical  Activity Questionnaire (IPAQ  short  version).
Results:  Out  of  938 patients, 91 (9.7%)  were hospitalized due  to COVID-19.  In a  univariate  analysis,  sex, age, and BMI  were all  associated with  hospitalizations  due to  COVID-19. Men had a higher  prevalence of hospitalization  (66.6%,  p=0.013). Patients older  than 65 years, obese,  and with preexisting  disease  had a higher  prevalence  of  COVID-19-related hospitalizations. In a  multivariate regression model, performance of  at  least  150 min/wk  (moderate)  and/or  75 min/wk  (vigorous)  physical  activity  was  associated with a lower  prevalence  of  hospitalizations  after  adjustment  for  age, sex, BMI, and preexisting  diseases (PR=0.657;  p=0.046).
Conclusions:  Sufficient  physical  activity  levels  were  associated  with a  lower  prevalence  of  COVID-19related hospitalizations.  Performing  at  least  150 minutes a  week  of  moderate-intensity, or  75 minutes a week  of  vigorous-intensity  physical  activity  was  associated  with  34.3%reduction in  prevalence.
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Results:
...
In the present  study, we observed the higher  prevalence  of  hospitalization  in older  patients, which could  be explained by  the  association  of  systemic inflammation (termed  “inflammaging17”)  in elderly people.  Interestingly, exercise  training  attenuates  aging  biomarkers and modulates the redox balance.12Master  athletes  have  better  redox balance and inflammatory  status compared  with  middle agematched controls.18  Thus, physical  activity  may  be a  strategy  to prevent  clinical  severity  in elderly persons  with  COVID-19.
Obesity  has  been  associated with  insufficient  physical  activity  and sedentary  behavior.19-22 Indeed, we found a  higher  proportion of  obese  patients with  insufficient  physical  activity.  Inflammation has  been described as  a key mechanism  in the  worsening  of  COVID-19 in  the  obese.23, 24  Interestingly, physical  activity  is recommended  as  part  of  weight  loss  for  obese adults (Evidence  Category  A).20,  25,  26  In addition, physical  activity  is  one of  the nonpharmacological  therapies  to reduce inflammatory  cytokines,27 which  may  be a  possible mechanism  of  protection  in patients infected with SARS-CoV-2.  It  has  been suggested  that  central  obesity  compromises  lung  ventilation and may  exacerbate COVID-19.28  Increased abdominal  obesity29  and obstructive sleep apnea30  are  common conditions  in obesity, and both are remarkablyimproved after  an  exercise  training  program.20, 25
Physical  activity  improves  immune system  response mainly  due to  the  amelioration  of recirculation of  immunoglobulins, neutrophils, natural  killer  cells, cytotoxic  T  cells, and  immature B Journal Pre-proof cells.4Additionally,  exercise prevents and treats numerous  COVID-19-associated  complications,  such as cardiac,  neurological,  and  metabolic disorders,22,  31  including  the  positive effect  on  the  renin-angiotensin system.32-34  Interestingly, acute  and chronic  exercise  training  promote changes  in  immune system.35  In fact, while  one session of  exercise  changes  most  immunological  markers  such asCD16-56 NK  cells, chronic  exercise  interferes  with a  smaller  proportion, this being  in  lymphocyte subpopulations  like  CD4+, CD8+, and CD20.35  Future  studies  are  needed  to better  understand the mechanisms involved in physical activity  and  its benefits  in patients with COVID-19.
This  is an observational  study  and the  results should  be  interpreted with  caution.  Although we found  an association  between physical  activity  and  lower  prevalence of  COVID-19-related hospitalizations, we did not  investigate  the  mechanisms involved in  this  relationship. All  participants filled out  the electronic  form  by  themselves  and possible bias  should be considered. However, we constructed  a quality  control  criterion  to reduce such biases.  We  did not  directly  measure physical  activity by  an accelerometer  device;  however, self-report  physical  activity  questionnaires  have been  largely  used in research,  and  a systematic review shows  that  the  IPAQ  shortform  has  excellent  test–retest  reliability (r=0.91).36  Considering  that  data  collection occurred  during  the  pandemic, it  is  possible that  some individuals have changed their  physical  activity  habits  as  a  result  of  the  preventive  measures  and  reported their  physical  activity  habits  during  this period.
 
Jiří Kroc
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Sadia Nikhat & Mohammad Fazilb
Science of the Total Environment 728 (2020) 138859
DOI: 10.1016/j.scitotenv.2020.138859
Abstact:
Since December 2019, a respiratory pandemic, named as coronavirus disease 2019 (Covid-19) caused by a new coronavirus named as SARS-CoV-2, has taken the world by storm. The symptoms are fever, malaise, and cough which resolve in a few days in most cases; but may progress to respiratory distress and organ failure. Transmission is through droplet infection or fomites, but other modes such as airborne transmission and oro-fecal transmission is also speculated. Research is underway to develop effective vaccines and medicines for the disease. In such a scenario, we present the measures described in Unani system of medicine for health protection during epidemics. Unani is a traditional system of medicine developed during the middle ages, which employs natural drugs of herbal, animal and mineral origin for treatment. In Unani medicine, during an epidemic, apart from isolation and quarantine, three measures are of utmost importance, (i) purification of surroundings using certain herbal drugs as fumigants or sprays, (ii) health promotion and immune-modulation, and (iii) use of health-protecting drugs and symptom-specific drugs. Drugs such as loban (Styrax benzoides W. G. Craib), sandroos (Hymenaea verrucosa Gaertn.) za'fran (Crocus sativus L.), vinegar etc. are prescribed in various forms. Scientific researches on these drugs reveal the presence of a number of pharmacologically active substances, which may provide a new insight into the management of infections and epidemics.
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From the text:
Unani system of medicine has its roots in ancient Greece, in the teachings of Hippocrates (460–377 BCE). The name Unani reflects its Hellenistic origin and is derived from the Yunan, the ancient name of Greece (Husain et al., 2010). Unani medicine flourished to its zenith during medieval ages (500–1500 CE) in the Muslim world, mostly in the Arabian peninsula, Persia, Egypt, Syria, ancient Mesopotamia, etc. Ergo it is also referred to as Greco-Arabian medicine and Persian medicineindifferentpartsof theworld(Islam, 2018).InIndia,itisintegrated into the national healthcare system and officially named as Unani medicine (Subbarayappa, 2001). UnanimedicineisbasedontheHippocratic concepts of mizaj (temperament) and akhlat (humors) (Husain et al., 2010). Famous scholars of Unani medicine include Ibn Sina (Latinized as Avicenna, 980–1035 CE), Zakariya Razi (Latinized as Rhazes, 865–925 CE), Ibn Rushd (Latinized as Averroes, 1126–1198 CE), and manymore(Islam, 2018).
 
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Margrit Shildrick
Article in Somatechnics · November 2019
DOI: 10.3366/soma.2019.0280
Abstract:
The focus of this article is the problematic of data in the life sciences with regard to the supposedly singular event of heart transplantation. In mainstream discourse, organ transplantation is seen as a straightforward exchange of body parts in which fatally deteriorating biological elements are replaced by more competent and enduring components. Post-transplant a variety of biological, immunological, and pharmaceutical data are collected and evaluated, with the success of the operation gauged against the clinical recovery of the recipient as determined by those measures. That simple picture fails to attend, however, to issues such as the historico-cultural context of the biomedical procedure, temporality, the phenomenological sense of self, the psycho-social imaginary, and even disregarded biological dimensions such as cellular microchimerism, all of which can deeply unsettle biomedical certainty. Drawing on my own participation in collaborative research, I rethink what counts as data and demonstrate the need to interweave multiple forms of knowledge in a data assemblage that mobilises new insights into the significance of transplantation and concorporeality.
Keywords: transplantation; hybridity; Deleuze; data assemblage; bioscience.
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Conclusions:
On a simple level, then, we need to rethink which data are relevant and what recipients should know. Alongside the usual biomedical infor­mation that grounds consent, the potential disruptions to identity should be discussed from the outset as anticipated rather than abnormal. Recipients need space in which to express their intuitions of internal difference, but the wider issue for all of us is how to rethink the cultural imaginaryof a singular embodied subject who is autonomous and distinct from her others. In place of ontological separation, there is an ethical imperative to think through at least concorporeality, but more radically assemblage where diverse elements conjoin – and split apart – in never settled processes of becoming. The insistence in current practice, that the pre-existing subject will live on essentially unchanged seems to me profoundly restrictive of alternative modes –and let’s call them data – that might better express the recipient experience.
In moving to a more intersectional approach to organ donation that accepts the need for a data assemblage and leaves behind the narrow positivism of biomedical advances, all sorts of difficult questions that take account of the shock to the body’s putative unity and identity-to-self are able to emerge. The post-operative patient knows that something fundamental has altered, that their sutured bodies intend a transformed mode of being-in-the-world, and they need support in thinking through how to live well in a hybrid, prostheticised body. Even in conventional approaches, the need to revamp healthcare practices to enable heart recipients to express their actual embodied experiences, without fear of ridicule, or being thought ungrateful or psychiatrically unstable, is clear. And that means transplant professionals need to rethink what is seen as unproblematically therapeutic, and to take a more critical approach to conventional data that opens up new forms. If we recognised more widely the symbiotic and unfixed intersection of biology and culture in the meaning of embodiment and rethought the epistemologies that dominate bioscience and its restrictive data habit, then it might be clear that it is precisely fixed boundaries that are the problem – not just for those undergoing radical interventions into the body, but for all of us. In any case, in postconventional thought, there is no pre-existing pure form of embodiment to restore – we are already hybrid, already more than one, already more than human. We are always in a process of becoming-other, even when appearing the same. In the age of technological transformations that contest the nature of human embodiment, the bioscientific approach alone is inadequate; and perhaps it would be better to start from the phenomenological point of disturbance.
Thinking through research assemblages in relation to the issues uncovered by recipient accounts mobilises the need to explore at least two major paths. First, we need innovative research methodologies that give up the search for incontrovertible quantifiable evidence, or indeed for qualitative data, that asserts the truth of any one discourse, including that of the respondent. Second, we need to radically rethink the relation between self and other by engaging with the notions of hybridity and concorporeality, and embrace the Deleuzian notion of assemblage. Whatever entangled data paths are taken, and they cannot be defined in advance, it is clear that outcomes will remain provisional at best and constantly open to transformation. If the conventional search for a coherent sense of bodily normativity is deeply damaging in its disavowal of the radical instances of disarray and disorder that embodiment may entail, then body shock requires new forms of data that do not close things down. The need is for novel modes of knowledge production for meaning-making that mobilise new relations with the embodied materialities of biomedicine. Such perspectives take heart transplan­tation out of the narrow confines of the clinic and into an entangled sphere where recipients, donor families, clinicians, academics, artists, and the general public come together to make their own meanings about the procedure. The exploration of new questions and possibilities facilitated by a critical engagement with multiple modes of intertwined data may unsettle the life sciences only to creatively reimagine them.
 
Jiří Kroc
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Alexander J Kastaniotis, Kaija J Autio & Remya R Nair
The Neuroscientist 27:2 (2020) 107385842093616
DOI: 10.1177/1073858420936162
Abstract
Fatty acids in mitochondria, in sensu stricto, arise either as β-oxidation substrates imported via the carnitine shuttle or through de novo synthesis by the mitochondrial fatty acid synthesis (mtFAS) pathway. Defects in mtFAS or processes involved in the generation of the mtFAS product derivative lipoic acid (LA), including iron-sulfur cluster synthesis required for functional LA synthase, have emerged only recently as etiology for neurodegenerative disease. Intriguingly, mtFAS deficiencies very specifically affect CNS function, while LA synthesis and attachment defects have a pleiotropic presentation beyond neurodegeneration. Typical mtFAS defect presentation include optical atrophy, as well as basal ganglia defects associated with dystonia. The phenotype display of patients with mtFAS defects can resemble the presentation of disorders associated with Coenzyme A (CoA) synthesis. A recent publication links these processes together based on the requirement of CoA for ACP maturation. MtFAS defects, CoA synthesis- as well as Fe-S cluster-deficiencies share lack of LA as a common symptom.
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Conclusions and future challenges
In contrast to disorders caused by mitochondrial β-oxidation defects, mtFAS or LA synthesis/attachment deficiencies have only recently entered the databases as diseases causing neurological defects. There is no doubt that the list of mtFAS disease alleles will expand to cover all or nearly all of the contributing factors, in addition to ACSF3, MCAT and MECR pathological variants currently known. With more data available in the near future, a clearer understanding of the processes leading to neurodegeneration may be achieved.
ACSF3 clearly has other roles in addition to providing malonyl-CoA for mtFAS leading to the more pleiotropic presentation of CMAMMA. But for the MCAT and MECR defect cases, the very strict neurological phenotype is remarkable. Neurons require a high level of oxidative phosphorylation. It may be argued that at least one of the alleles carried by mtFAS patients still has some residual function, which may be sufficient to support cell viability in other cell types. Nevertheless, if the role of mtFAS is so essential in mitochondrial function, why are we not able to observe severe effects on other patient tissues with a high energy demand like skeletal muscle or heart? Owing to the central roles of CoA in metabolism and Fe-S clusters in the function of multiple important enzymes, it is evident why defects in these processes have much more pleiotropic consequences than mtFAS dysfunctions. But why are mutations that affect LA synthesis and attachment so much more pleiotropic? There is currently no answer to these questions, but there is a suspicion. Unlike yeast, where mtFAS is essential for respiration, most mammalian cells carry out β-oxidation in mitochondria. The notable exception from this observation are neurons. Hence, the question must be asked if there is a route for fatty acid breakdown intermediates to ACP in tissues carrying out mitochondrial β-oxidation. There may be alternative explanations, for example reduced motility of mitochondria with mtFAS defects. Mitochondria in mtFAS deficient cells both in yeast an mammals display severe morphological changes (A. Kastaniotis and others, 2004; Monteuuis and others, 2017; Torkko and others, 2001), which may also be associated with a diminished ability to move around in the cell. In neurons, mitochondria often are transported for long distances along the axons (Saxton and Hollenbeck, 2012), and disturbed transport processes
may be an alternative explanation for the neuron specificity of mtFAS disorders. Research addressing these hypotheses is necessary.
The remarkable contribution of Lambrechts and others in 2019 has been able to help in our understanding of the similarities of CoPAN, PKAN, MEPAN and other mtFAS deficiency disorders. The existence of a common denominator in these disorders – holo-ACP – also points to a common defect that may in the future be addressed pharmacologically: LA deficiency. In light of our current understanding that free LA provided in the diet is not available for attachment to ketoacid dehydrogenase complexes, there is no doubt that it will be a challenge to find a compound that may be used for enzyme lipoylation. But such a molecule – being accepted as transfer substrate by LIPT1 and LIPT2, able to cross the cell and mitochondrial membranes and to overcome the blood-brain-barrier – would likely be of tremendous help for many patients. No candidate molecule meeting all these challenges has been found to date, and efforts towards finding promising compounds are necessary.
ACP has emerged one of the key players shared by CoPAN, PKAN and MEPAN syndromes. Acylation of ACP must clearly play a role in its proposed function to coordinate IMBE. But more profoundly, the 4’phosphopantetheinylation of ACP appears to be one of the most critical steps in cellular function. If Lambrechts and co-workers are correct, this process must be very sensitive to the concentration of CoA in the cell. Hence, if mtFAS is an intramitochondrial sensor of cellular energy state, could ACP serve as a mitochondrial sensor for CoA, one of the most central compounds of cellular metabolism?
 
Jiří Kroc
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Stephanie Seneff, Greg Nigh, Anthony M. Kyriakopoulos & Peter A McCullough
Food and Chemical Toxicology 164 (June 2022) 113008
DOI:10.22541/au.164276411.10570847/v1
Abstract:
The mRNA SARS-CoV-2 vaccines were brought to market in response to the widely perceived public health crises of Covid-19. The utilization of mRNA vaccines in the context of infectious disease had no precedent, but desperate times seemed to call for desperate measures. The mRNA vaccines utilize genetically modified mRNA encoding spike proteins. These alterations hide the mRNA from cellular defenses, promote a longer biological half-life for the proteins, and provoke higher overall spike protein production. However, both experimental and observational evidence reveals a very different immune response to the vaccines compared to the response to infection with SARS-CoV-2. As we will show, the genetic modifications introduced by the vaccine are likely the source of these differential responses. In this paper, we present the evidence that vaccination, unlike natural infection, induces a profound impairment in type I interferon signaling, which has diverse adverse consequences to human health. We explain the mechanism by which immune cells release into the circulation large quantities of exosomes containing spike protein along with critical microRNAs that induce a signaling response in recipient cells at distant sites. We also identify potential profound disturbances in regulatory control of protein synthesis and cancer surveillance. These disturbances are shown to have a potentially direct causal link to neurodegenerative disease, myocarditis, immune thrombocytopenia, Bell’s palsy, liver disease, impaired adaptive immunity, increased tumorigenesis, and DNA damage. We show evidence from adverse event reports in the VAERS database supporting our hypothesis. We believe a comprehensive risk/benefit assessment of the mRNA vaccines excludes them as positive contributors to public health, even in the context of the Covid-19 pandemic. 
 
Jiří Kroc
added an update
Cole B. Hirschfeld, Leslee J. Shaw, Michelle C. Williams, Ryan Lahey, Todd C. Villines, Sharmila Dorbala, Andrew D. Choi, Nishant R.Shah,  David A. Bluemke, Daniel S. Berman, Ron Blankstein, MarosFerencik, Jagat Narula, David Winchester, Eli Malkovskiy, Benjamin Goebel, Michael J. Randazzo, Juan Lopez-Mattei, Purvi Parwani, Joao V. Vitola, Rodrigo J. Cerci, Nathan Better, Paolo Raggi, Bin Lu, Vladimir Sergienko, Valentin Sinitsyn, Takashi Kudo, Bjarne Linde Nørgaard, Pál Maurovich-Horvat, Yosef A. Cohen, Thomas N.B. Pascual, Yaroslav Pynda, Maurizio Dondi, Diana Paez, Andrew J. Einstein, on behalf of the INCAPS-COVID Investigators Group
JACC. Cardiovascular imaging 14:9 (2021)
DOI: 10.1016/j.jcmg.2021.03.007
Abstract:
Objectives This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.
Background The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.
Methods Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.
Results Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis.
Conclusions We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection.
Key Words: cardiovascular disease, cardiovascular imaging, coronavirus COVID-19, diagnostic cardiovascular procedure
 
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Marcello Marcı & Patrizia Ajovalasit
Cardiology Research and Practice (2009) ID 281389, 3 pages
DOI: 10.4061/2009/281389
Abstract:
We report about an infant affected by dilated cardiomyopathy (CMP) in whom metabolic investigations evidenced mediumchain-acyl-CoA dehydrogenase deficiency (MCADD), that is one of three types of inherited disorders of mitochondrial fatty-acid β-oxidation. Long-chain and very long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficits are recognized as responsible of hypertrophic or, less frequently, dilated cardiomyopathy (CMP) in childhood. Otherwise, to our knowledge, no case of MCADD associated to dilated CMP has been reported in literature.
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Despite advances in drug therapy dilated CMP remains one of the leading cause of death and heart transplant in childhood. Its incidence in infancy is estimated in about 4.4 cases per 100000 per year, with a high mortality: 50%–60% at two years.
Moreover about one third of patients dies or undergoes heart transplant in the first year [1, 2]. Although the most of cases (66%) are defined “idiopathic”, some CMP may have an identifiable cause [1–4]. Identification of underlying cause  of CMP in children may improve outcome after specific treatment [1, 3, 4]. Positive family history of heart failure, sudden death, or genetic syndrome is usually predictive of a probable cause for CMP [4].
 
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Rebecca Jane Joseph, Hooi-Leng Ser, Yi-He Kuai, Loh Teng-Hern Tan, Valliammai Jayanthi Thirunavuk Arasoo, Vengadesh Letchumanan, Lijing Wang, Priyia Pusparajah, Bey-Hing Goh, Nurul-Syakima Ab Mutalib, Kok-Gan Chan & Learn-Han Lee
Antibiotics 10 (2021) 719
DOI: 10.3390/ antibiotics10060719
Abstract and figures
Bacterial vaginosis (BV) has been reported in one-third of women worldwide at different life stages, due to the complex balance in the ecology of the vaginal microbiota. It is a common cause of abnormal vaginal discharge and is associated with other health issues. Since the first description of anaerobic microbes associated with BV like Gardnerella vaginalis in the 1950s, researchers have stepped up the game by incorporating advanced molecular tools to monitor and evaluate the extent of dysbiosis within the vaginal microbiome, particularly on how specific microbial population changes compared to a healthy state. Moreover, treatment failure and BV recurrence rate remain high despite the standard antibiotic treatment. Consequently, researchers have been probing into alternative or adjunct treatments, including probiotics or even vaginal microbiota transplants, to ensure successful treatment outcomes and reduce the colonization by pathogenic microbes of the female reproductive tract. The current review summarizes the latest findings in probiotics use for BV and explores the potential of vaginal microbiota transplants in restoring vaginal health.
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Conclusions (a selection)
... In this review, probiotics, which mainly comprises Lactobacillus spp. seem to be a beneficial management plan as they help to reinstate balance in the vaginal microbiome. Reid et al. attempted to explore the benefits of two common inhabitants of the female urogenital tract, L. rhamnosus GR-1 and L. reuteri RC14, as probiotics in vaginal health [308]. The team noticed a significant increase in vaginal Lactobacillus at day 28 and 60, accompanied by a significant depletion in yeast and a significant reduction in coliforms for women treated with the probiotics when compared to control (age range: 19–46). Their results demonstrated that this probiotic mixture is not only safe for daily use in healthy women but also prevents vaginal colonization by potentially pathogenic bacteria and yeast. To date, probiotics are still not listed as a recommended treatment as a Cochrane Review published in 2009 highlighted the lack of evidence in favor or against its recommendation in the treatment of BV [309,310]. As mentioned by Senok et al., the major challenges in comparing the outcome of different trials are the variation in study design and probiotic preparations [309,311]. Even though no adverse effects were reported with probiotics administration as opposed to antibiotic use in BV, higher-quality studies are required to validate its efficacy. From the gathered literature, administration of high doses probiotics of at least 109 CFU and using a probiotics cocktail may confer greater benefits than a single strain probiotic. Besides optimizing the dose and number of strains included in the probiotic formulation, the administration route is also deemed to be another critical factor when designing the treatment plan for BV. So far, clinical studies conducted to study the efficacy of probiotics in BV were delivered either orally or intravaginally. Over these years, it was observed that oral probiotics could be passed to the urogenital and vaginal system from the gut through unknown mechanisms [292,312]. However, the probiotics’ efficacy could be affected based on the ability to survive the harsh environment in the gastrointestinal system, and it would take much longer to reach the vagina. In addition to that, probiotics could be considered as an adjunct to antibiotic treatment, but more evidence is required before it is recommended. There is also another possibility to combine the use of probiotics with prebiotics as synbiotic to increase colonization rate, preventing biofilm formation, and restore the normal flora in the vagina. ...
 
Jiří Kroc
added an update
Richard Wong, Stefan Geyer, Wolfgang Weninger, Jean-Claude Guimberteau & Jason K. Wong
Abstract:
The skin is often viewed as a static barrier that protects the body from the outside world. Emphasis on studying the skin's architecture and biomechanics in the context of restoring skin movement and function is often ignored. It is fundamentally important that if skin is to be modeled or developed that we do not only focus on the biology of skin but also aim to understand its mechanical properties and structure in living dynamic tissue. In this review, we describe the architecture of skin and patterning seen in skin as viewed from a surgical perspective and highlight aspects of the microanatomy that have never fully been realized and provide evidence or concepts that support the importance of studying living skin's dynamic behaviour. We highlight how the structure of the skin has evolved to allow the body dynamic form and function; and how injury, disease or ageing results in a dramatic changes to the microarchitecture and change physical characteristics of skin. Therefore, appreciating the dynamic microanatomy of skin from the deep fascia through to the skin surface is vitally important from a dermatological and surgical perspective. This focus provides an alternative perspective and approach to addressing skin pathologies and skin ageing.This article is protected by copyright. All rights reserved.
Key words: ageing – architecture – dynamic anatomy – patterning – skin
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This review provides a very important starting point to all researchers who are working in the area of mathematical modeling of biological structures.
The mechanical nature of the problems related to functioning of all skin layers provides us with easier, mutual identification of real and simulated processes undergoing in living skin.
This work is recommended to all who are searching for a perspective and easy to grasp area of multiscale modelling techniques applied to functioning of biological structures.
More about the paper and its use in modelling of skin properties can be found in the project:
 
Jiří Kroc
added an update
Les Gordon, Mathieu Pasquier, Hermann Brugger & Peter Paal
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine (2020) 28:14
DOI: 10.1186/s13049-019-0685-4
Abstract
Background: Autoresuscitation describes the return of spontaneous circulation after termination of resuscitation (TOR) following cardiac arrest (CA). We aimed to identify phenomena that may lead to autoresuscitation and to provide guidance to reduce the likelihood of it occurring.
Materials and methods: We conducted a literature search (Google Scholar, MEDLINE, PubMed) and a scoping review according to PRISMA-ScR guidelines of autoresuscitation cases where patients undergoing CPR recovered circulation spontaneously after TOR with the following criteria: 1) CA from any cause; 2) CPR for any length of time; 3) A point was reached when it was felt that the patient had died; 4) Staff declared the patient dead and stood back. No further interventions took place; 5) Later, vital signs were observed. 6) Vital signs were sustained for more than a few seconds, such that staff had to resume active care.
Results: Sixty-five patients with ROSC after TOR were identified in 53 articles (1982–2018), 18 (28%) made a full recovery.
Conclusions: Almost a third made a full recovery after autoresuscitation. The following reasons for and recommendations to avoid autoresuscitation can be proposed: 1) In asystole with no reversible causes, resuscitation efforts should be continued for at least 20 min; 2) CPR should not be abandoned immediately after unsuccessful defibrillation, as transient asystole can occur after defibrillation; 3) Excessive ventilation during CPR may cause hyperinflation and should be avoided; 4) In refractory CA, resuscitation should not be terminated in the presence of any potentially-treatable cardiac rhythm; 5) After TOR, the casualty should be observed continuously and ECG monitored for at least 10 min.
Keywords: Autoresuscitation, Cardiopulmonary resuscitation, Emergency medicine, Hyperventilation, Lazarus phenomenon, Resuscitation, Resuscitation orders
From Discussion:
... Although patients exhibiting theaboveclinicalfindings are assumed to have passed the “point of no return” and become unsalvageable, in fact death is not an instantaneous event but takes place over time. Sporadic ECG activity in the absence of a circulation can occur for many minutes after death is diagnosed [1, 33, 39, 44], and this can confound the Academy’suseof asystole as an indicator of death. Thus, an essential requirement when defining autoresuscitation is the presence of a circulation, because death determination depends on the cessation of circulation, not just of cardiac electrical activity [45]. In addition, a recent animal study indicated that sporadic cortical neuronal activity may be present for 2 hours following cardiac arrest [46]. ...
 
Jiří Kroc
added an update
Wendy Menigoz, Tracy T. Latz, Robin A. Ely, Cimone Kamei, Gregory Melvin, Drew Sinatra
Explore 16 (2020) 152160
Abstract:
Earthing (also known as grounding) refers to the discovery that bodily contact with the Earth’s natural electric charge stabilizes the physiology at the deepest levels, reduces inflammation, pain, and stress, improves blood flow, energy, and sleep, and generates greater well-being. Such effects are profound, systemic, and foundational, and often develop rapidly. Earthing is as simple as routinely walking barefoot outdoors and/or using inexpensive grounding systems indoors while sleeping or sitting, practices that restore a lost and needed electric connection with the Earth. Some 20 studies to date have reported intriguing evidence of wide and significant physiological improvements when the body is grounded vs. non-grounded. The research, along with numerous anecdotal reports, demonstrates that Earthing clearly deserves inclusion in the clinical practice of preventive, alternative, and lifestyle medicine and has great potential to render these approaches more effective.
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Excerpts from the text:
Robin A. Ely, MD, Center for Integrative Medicine, Potomac, Maryland
Ongoing studies are providing increasing evidence for the hypothesis that a lack of Earthing is a significant factor, one of many, contributing to the striking escalation of chronic diseases in our generation. Earthing has been an integral part of human life, normative for the vast experience of mankind. It is only with the advent of shelter and footwear made of insulating materials that humans now spend their lives without any time in a 24 h period being electromagnetically connected to the Earth. I recommend Earthing to anyone whowill listen. I have found it to be very beneficial in my own life and in others who have taken heed and put into practice various Earthing methods, including, when available, walking barefoot on soil, grass, or sand, or using Earthing products indoors such as mats, throws, and patches.
Drew Sinatra, ND, LAc., Clear Center of Health, Mill Valley, California
I have found that fibromyalgia responds well to daily Earthing. An example was a 45-year-old female patient who followed my recommendation for Earthing in bed. About a month later she reported that her body pain had improved significantly, and she was sleeping more soundly during the night.
Discussion: Applying Earthing
One of the great advantages of Earthing as a lifestyle concept is the simplicity of application. Walking barefoot outdoors is obviously the most natural way. A grassy park, yard, or sandy beach are ideal locations. For other natural terrain, as well as concrete surfaces, Earthing footwear can be purchased to protect the feet. Do any online search. Another option is barefoot gardening. Even getting the hands in the soil will provide an Earthing effect.
By far, the most convenient and most popular Earthing location is inside the home and/or office, where Earthing can be easily incorporated while sitting (working or relaxing) and sleeping. Earthing does not interfere with either activity, and can be done over many hours each day. Earthing products are in contact with the Earth through a cord inserted into the ground/earth port of a wall outlet (connected to the grounding system of a house or office) or attached to a ground rod placed in soil outside. Clinicians can ground patients in the office (even in the waiting room before or after an appointment) for sessions of a half-hour or more utilizing grounding products such as conductive chairs, mats, and patches. 
 
Jiří Kroc
added an update
Richard Brown & Gaétan  Chevalier
Open Journal of Preventive Medicine 5  (2015)  159-168
DOI: 10.4236/ojpm.2015.54019
Abstract
Objective:  Research  continues to  show  that  being  connected  to  the  earth  can  increase the potential of the body to  scavenge free radicals.  This study examined  the effect  of just  one hour  of  grounding on  blood  viscosity while subjects participated  in  gentle yoga  exercises designed  to  initiate  minor inflammation.  Design:  In  this double blind  model,  twenty-eight  (28)  subjects met  at  the  Bower- man  Sports  Medicine Clinic  on  the campus of  the University  of Oregon  and  were grounded  to  the earth  via  contact  with  a  grounded  yoga  mat or  were  sham-grounded.  Ten  yoga  exercises  were repeated  five  times  over  a  one-hour period.  Blood  was  taken  pre  and  post  exercise and  analyzed  for blood  viscosity using  a  scanning  capillary  viscometer.  Results:  Subjects  connected  to  the  earth  significantly  reduced  their  post  exercise systolic  blood  viscosity  (p  =  0.03)  and  diastolic  blood  viscosity  (p  = 0.03).  Conclusion:  Grounding  has  the  ability  to  affect  exercise induced  inflammation,  thereby  reducing  blood  viscosity.
Keywords Earthing,  Grounding,  Yoga,  Yoga  Mats,  Blood  Viscosity
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Conclusion
Blood  viscosity  may  be an  early  predictor  of  chronic disease.  Since  equipment  is  now  available  to  reliably measure this  parameter,  more investigations  should  be  undertaken.  Habits,  as  well  as  certain  medications,  can lower  blood viscosity.  But  medications  are often  expensive and  present  unwanted  side effects.  A  potential treatment  that  presents  no  downside  is  grounding the  body to  the  earth.  In  this  study  it  was  shown that,  despite mild  exercise  that can  raise  blood  viscosity  temporarily,  blood  viscosity  was  lowered  at both  the  systolic  and  diastolic ends  of  the cardiac cycle in  subjects  using  grounded  yoga  mats.  Earthing  has  the  ability  to  affect  exercise-induced inflammation  by  reducing  blood viscosity. 
 
Jiří Kroc
added an update
Gaetan Chevalier, Stephen T. Sinatra, James L. Oschman, PhD & Richard M. Delany
THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE  19:2 (2013) 102–110
DOI: 10.1089/acm.2011.0820
Abstract Objectives: Emerging research is revealing that direct physical contact of the human body with the surface of the earth (grounding or earthing) has intriguing effects on human physiology and health, including beneficial effects on various cardiovascular risk factors. This study examined effects of 2 hours of grounding on the electrical charge (zeta potential) on red blood cells (RBCs) and the effects on the extent of RBC clumping. Design/interventions: Subjects were grounded with conductive patches on the soles of their feet and palms of their hands. Wires connected the patches to a stainless-steel rod inserted in the earth outdoors. Small fingertip pinprick blood samples were placed on microscope slides and an electric field was applied to them. Electrophoretic mobility of the RBCs was determined by measuring terminal velocities of the cells in video recordings taken through a microscope. RBC aggregation was measured by counting the numbers of clustered cells in each sample. Settings/location: Each subject sat in a comfortable reclining chair in a soundproof experiment room with the lights dimmed or off. Subjects: Ten (10) healthy adult subjects were recruited by word-of-mouth. Results: Earthing or grounding increased zeta potentials in all samples by an average of 2.70 and significantly reduced RBC aggregation. Conclusions: Grounding increases the surface charge on RBCs and thereby reduces blood viscosity and clumping. Grounding appears to be one of the simplest and yet most profound interventions for helping reduce cardiovascular risk and cardiovascular events.
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Conclusions
Increased blood viscosity in the general population may be a predictor of cardiovascular events because of its influences on hypertension, thrombogenesis, ischemia, and arthrogenesis. Unfortunately, blood viscosity has become a forgotten risk factor and is rarely measured in clinical practice.45 Interventions that reduce blood viscosity and RBC aggregation are important. Statins appear to be effective for modulating blood viscosity, but can have serious side-effects including death.3 Moreover, some patients have statin intolerance. The use of a safe effective anti-inflammatory strategy that is not dependent on isoprenoid inhibition is therefore desirable. Grounding or earthing the body is virtually harmless. To date, there has been no systematic study of the effects of grounding on BP. However, there are anecdotal reports that patients using blood-thinning drugs, such as warfarin (Coumadin), need to have their clotting time monitored when they begin to make more frequent conductive contact with the earth. When physicians recommend evidencebased, harmless, and simple natural interventions, alleviation of human suffering and improved quality of life can be realized. The findings in this pilot study indicate that grounding has a safe and significant effect on zeta potential and that further study is warranted.
 
Jiří Kroc
added an update
Alma Rosa Lezama Toledo, Germán Rivera Monroy, Felipe Esparza Salazar, Jea-Young Lee, Shalini Jain, Hariom Yadav & Cesario Venturina Borlongan
Int. J. Mol. Sci. 2022, 23(3), 1184;
DOI: 10.3390/ijms23031184
Abstract:
Human lifestyle and dietary behaviors contribute to disease onset and progression. Neurodegenerative diseases (NDDs), considered multifactorial disorders, have been associated with changes in the gut microbiome. NDDs display pathologies that alter brain functions with a tendency to worsen over time. NDDs are a worldwide health problem; in the US alone, 12 million Americans will suffer from NDDs by 2030. While etiology may vary, the gut microbiome serves as a key element underlying NDD development and prognosis. In particular, an inflammation-associated microbiome plagues NDDs. Conversely, sequestration of this inflammatory microbiome by a correction in the dysbiotic state of the gut may render therapeutic effects on NDDs. To this end, treatment with short-chain fatty acid-producing bacteria, the main metabolites responsible for maintaining gut homeostasis, ameliorates the inflammatory microbiome. This intimate pathological link between the gut and NDDs suggests that the gut-brain axis (GBA) acts as an underexplored area for developing therapies for NDDs. Traditionally, the classification of NDDs depends on their clinical presentation, mostly manifesting as extrapyramidal and pyramidal movement disorders, with neuropathological evaluation at autopsy as the gold standard for diagnosis. In this review, we highlight the evolving notion that GBA stands as an equally sensitive pathological marker of NDDs, particularly in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and chronic stroke. Additionally, GBA represents a potent therapeutic target for treating NDDs.
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Conclusions
A better understanding of the GBA could provide novel perspectives of NDD pathophysiology and therapeutic approaches. Profiling of the microbiome signature of specific NDDs may reveal distinct microbiota associated with gut dysbiosis. In the same token, these microbiota may serve as therapeutic targets for treating NDDs. To this end, an inflammatory microbiome closely approximates NDD progression, and dampening this harmful microbiome retards neurodegeneration. In particular, transplanting stem cells into the gut of preclinical models of NDDs reduces the inflammatory microbiome not just in the gut but also in the brain accompanied by improvement in neurological functions. Whereas the present paper focuses on just four NDDs, other neurological disorders present with similar GBA alterations that accompany the disease progression, including Huntington’s disease [139,140,141] and multiple sclerosis [142,143,144]. Accordingly, disease-specific tailoring of stem cell transplantation targeting GBA may provide disease-modifying outcomes for these neurological disorders. The fact that the GBA plays a significant role in disease pathology advances the innovative concept of GBA-based therapeutics for NDDs.
 
Jiří Kroc
added an update
Rashad Alkasir, Jing Li, Xudong Li, Miao Jin & Baoli Zhu
Protein Cell 2017, 8(2):90–102
DOI: 10.1007/s13238-016-0338-6
Abstract
Dementia is a comprehensive category of brain diseases that is great enough to affect a person's daily functioning. The most common type of dementia is Alzheimer's disease, which makes most of cases. New researches indicate that gastrointestinal tract microbiota are directly linked to dementia pathogenesis through triggering metabolic diseases and low-grade inflammation progress. A novel strategy is proposed for the management of these disorders and as an adjuvant for psychiatric treatment of dementia and other related diseases through modulation of the microbiota (e.g. with the use of probiotics).
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Summary
Microbial colonization of the gut plays a key role in the postnatal development and maturation of the immune, endocrine and even neural systems, these processes are key factors underpinning CNS signalling. Indeed, understanding the gut microbiota is important in relation to inflammation and metabolic diseases that have a direct relation to the AD pathogenesis. Moreover, comparative analysis of gut microbiota may enable further novel vision into the complex biology of AD, which is very important in order to take preventive measure such as early diagnosis, identification of new therapeutic targets and development of novel drugs. Thus, modulation of gut microbiota (by probiotics or other dietary intervention) or direct targeting of gut microbiota enzymes (by pharmacological inhibitors or activators) may be a growing area for pharmaceutical and functional food industries, with the goal of decreasing the widespread growth of adiposity, insulin resistance, AD, and other metabolic diseases. 
 
Jiří Kroc
added an update
Helen Fogarty, Liam Townsend, Hannah Morrin, Azaz Ahmad, Claire Comerford, Ellie Karampini, Hanna Englert, Mary Byrne, Colm Bergin, Jamie M. O’Sullivan, Ignacio Martin-Loeches, Parthiban Nadarajan, Ciaran Bannan, Patrick W. Mallon, Gerard F. Curley, Roger J. S. Preston, Aisling M. Rehill, Dennis McGonagle, Cliona Ni Cheallaigh, Ross I. Baker, Thomas Renné, Soracha E. Ward, James S. O’Donnell, the Irish COVID-19 Vasculopathy Study (iCVS) investigators
Journal of Thrombosis and Haemostasis 19:10 (2021) 2546-2553
DOI: 10.1111/jth.15490
BRIEF REPORT
Abstract
Background
Persistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS-CoV-2 infection. The biological mechanisms underlying this “long COVID” syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID-19.
Objectives
To assess whether endothelial cell activation may be sustained in convalescent COVID-19 patients and contribute to long COVID pathogenesis.
Patients and Methods
Fifty patients were reviewed at a median of 68 days following SARS-CoV-2 infection. In addition to clinical workup, acute phase markers, endothelial cell (EC) activation and NETosis parameters and thrombin generation were assessed.
Results
Thrombin generation assays revealed significantly shorter lag times (p < .0001, 95% CI −2.57 to −1.02 min), increased endogenous thrombin potential (p = .04, 95% CI 15–416 nM/min), and peak thrombin (p < .0001, 95% CI 39–93 nM) in convalescent COVID-19 patients. These prothrombotic changes were independent of ongoing acute phase response or active NETosis. Importantly, EC biomarkers including von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), and factor VIII were significantly elevated in convalescent COVID-19 compared with controls (p = .004, 95% CI 0.09–0.57 IU/ml; p = .009, 95% CI 0.06–0.5 IU/ml; p = .04, 95% CI 0.03–0.44 IU/ml, respectively). In addition, plasma soluble thrombomodulin levels were significantly elevated in convalescent COVID-19 (p = .02, 95% CI 0.01–2.7 ng/ml). Sustained endotheliopathy was more frequent in older, comorbid patients, and those requiring hospitalization. Finally, both plasma VWF:Ag and VWFpp levels correlated inversely with 6-min walk tests.
Conclusions
Collectively, our findings demonstrate that sustained endotheliopathy is common in convalescent COVID-19 and raise the intriguing possibility that this may contribute to long COVID pathogenesis.
ESSENTIALS
• Ongoing endotheliopathy is a common finding in convalescent COVID-19 patients and is independent of the acute phase response.
• Plasma FVIII:C levels and thrombin generation are significantly increased in convalescent COVID-19 patients compared to healthy controls.
• Plasma VWF:Ag, VWFpp and sTM levels remain persistently elevated in a proportion of patients following apparent resolution of acute COVID-19.
• Markers of endotheliopathy correlate inversely with 6-min walk tests in patients with ongoing symptoms after COVID-19.
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From the results:
...
In conclusion, our data demonstrate for the first time that sustained EC activation is common up to 10 weeks following acute SARS-CoV-2 infection. Importantly, this persistent endotheliopathy appears to occur independently of ongoing acute phase response or NETosis and is associated with enhanced thrombin generation potential. We postulate that shedding of TM from EC may play a role in modulating the loss of normal EC quiescence. These findings are interesting given the critical role played by endotheliopathy in the pathogenesis of acute COVID-19. However, further adequately powered clinical trials will be required to determine whether this sustained EC activation and coagulation activation has a role in (1) stratifying patients at increased risk of thrombotic events after resolution of acute SARS-CoV-2 infection who may benefit from extended duration postdischarge thromboprophylaxis and/or (2) the pathogenesis of long COVID syndrome.
 
Jiří Kroc
added an update
M. Marizzoni, A. Cattaneo, P. Mirabelli, C. Festari, N. Lopizzo, Valentina Nicolosi, E. Mombelli, M. Mazzelli, D. Luongo, D. Naviglio, L. Coppola, M. Salvatore, G. Frisoni
Journal of Alzheimer's disease: JAD 78(2):683-697 (Nov 2020)
DOI: 10.3233/JAD-200306
Abstract
Background:Metagenomic data support an association between certain bacterial strains and Alzheimer’s disease (AD), but their functional dynamics remain elusive.
Objective:To investigate the association between amyloid pathology, bacterial products such as lipopolysaccharide (LPS) and short chain fatty acids (SCFAs: acetate, valerate, butyrate), inflammatory mediators, and markers of endothelial dysfunction in AD.
Methods:Eighty-nine older persons with cognitive performance from normal to dementia underwent florbetapir amyloid PET and blood collection. Brain amyloidosis was measured with standardized uptake value ratio versus cerebellum. Blood levels of LPS were measured by ELISA, SCFAs by mass spectrometry, cytokines by using real-time PCR, and biomarkers of endothelial dysfunction by flow cytometry. We investigated the association between the variables listed above with Spearman’s rank test.
Results:Amyloid SUVR uptake was positively associated with blood LPS (rho≥0.32, p≤0.006), acetate and valerate (rho≥0.45, p < 0.001), pro-inflammatory cytokines (rho≥0.25, p≤0.012), and biomarkers of endothelial dysfunction (rho≥0.25, p≤0.042). In contrast, it was negatively correlated with butyrate (rho≤–0.42, p≤0.020) and the anti-inflammatory cytokine IL10 (rho≤–0.26, p≤0.009). Endothelial dysfunction was positively associated with pro-inflammatory cytokines, acetate and valerate (rho≥0.25, p≤0.045) and negatively with butyrate and IL10 levels (rho≤–0.25, p≤0.038).
Conclusion:We report a novel association between gut microbiota-related products and systemic inflammation with brain amyloidosis via endothelial dysfunction, suggesting that SCFAs and LPS represent candidate pathophysiologic links between the gut microbiota and AD pathology.
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Selection from the Discussion:
...
The theory of inflammaging describes the low grade, chronic, systemic inflammation in aging, in (“sterile” inflammation)[75]. While the features of inflammaging remain “normal” or “subclinical” in many elderly individuals, a portion of individuals (postulated to have a “high responder inflammatory genotype”) may shift to age-associated diseases[76]. This shift has been proposed to serve as a prodrome or an exacerbating factor for development of AD[77]. Among the major identified sources of inflammaging, there are endogenous host-derived cell debris, amyloids, free radicals, immunosenescence aswell as products and metabolites produced by the GMB[78]. Thus, our results fit well the hypothesis that poses inflammaging as the link between the gut microbiome alteration, that triggers and sustains systemic inflammation, and the inflammation leading the on set of the pathological hallmarks of AD[79].
... 
 
Jiří Kroc
added an update
Monica H Carlsen, Bente L Halvorsen, Kari Holte, Siv K Bøhn, Steinar Dragland, Laura Sampson, Carol Willey, Haruki Senoo, Yuko Umezono, Chiho Sanada, Ingrid Barikmo, Nega Berhe, Walter C Willett, Katherine M Phillips, David R Jacobs Jr & Rune Blomhoff
Nutrition Journal  9:3 (2010) 1-11
doi: 10.1186/1475-2891-9-3.
Abstract
Background: A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies.
Methods: We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table.
Results: The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values.
Conclusions: This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than nonplant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.
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Additional file 1: The Antioxidant Food Table, Carlsen et al. 2010. the main results of the present study; the table includes all the 3139 products with product descriptions, details and antioxidant analysis results, categorized into 24 categories and arranged alphabetically within each category.
OR
 
Jiří Kroc
added an update
Jiri Kroc
Motivation
Everyone who is carrying on research in the intersection of biology, mathematics, and computations is very well aware of our inability to capture the processing of information within biological structures properly.
Therefore, the simulation of GoL presented in this share, along with other shares of other authors, aims to raise the attention of the general scientific community about the above-mentioned intersection.
Surprisingly, when the right mathematical formalism is found, apparently very complicated emergent processes can be described by quite simple mathematical descriptions, as is exactly happening in the 'Game of Life' and similar computational models that are all expressing unprecedented complexity.
Description
This is a preliminary research output, which occurred as a side result during research on modifications of the 'Game of Life' proposed by John Conway. Such scientifically and visually appealing simulation had arisen among many others where the observed structures might be interesting to other researchers. More will appear in a couple of months, stay tuned.
In general, it is observed that emergent structures of various types arise within this specific cellular automaton, all of them are having period of two. What is surprising is the fact that those structures are long range correlated, and some of them even turn by ninety degrees. From a certain point of view, we can say that the observed emergents posses a very stable binary behavior that deserves a deeper interest. Surprisingly, no moving emergents were observed yet in this type of cellular automaton.
More videos and the code will occur here:
A sample video from an ongoing research:
Two subsequent snapshot shown:
 
Oleksandr P. Romanchuk
added a research item
Introduction Sarcopenia, an age-associated phenomenon, is characterized by the reduced skeletal muscle mass and function. Research studies indicate that a wide range of factors can play a key role in the onset of muscle atrophy and its progression, especially during old age. However, the pathophysiology of this event is not well understood and there are many unresolved issues yet. Performing different training methods (aerobic, resistance, and concurrent) is among the strategies that may be beneficial for the prevention and improvement of sarcopenia by affecting the signaling pathways of muscle cells. On the other hand, the way in which this type of training affects the signaling pathways involved in sarcopenia has not been well understood. Even the previous research has been incapable of well introducing an effective training method for the elderly at risk for sarcopenia. Generally, in this review article, we investigate and summarize the important and key mechanisms that may contribute to sarcopenia. In the following, we have examined the effect of regular physical activity on cellular signaling pathways involved in sarcopenia, as well as the usefulness of aerobic, resistance, and concurrent activities in adaptation and prevention of the pathology of sarcopenia in the elderly.
Jiří Kroc
added an update
Tiziana Bisogno, Anna Lauritano & Fabiana Piscitelli
Life 11:9 (2021) 934
DOI: 10.3390/life11090934
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease that progresses from mild cognitive impairment to severe dementia over time. The main clinical hallmarks of the disease (e.g., beta-amyloid plaques and neurofibrillary tangles) begin during preclinical AD when cognitive deficits are not yet apparent. Hence, a more profound understanding of AD pathogenesis is needed to develop new therapeutic strategies. In this context, the endocannabinoid (eCB) system and the gut microbiome are increasingly emerging as important players in maintaining the general homeostasis and the health status of the host. However, their interaction has come to light just recently with gut microbiota regulating the eCB tone at both receptor and enzyme levels in intestinal and adipose tissues. Importantly, eCB system and gut microbiome, have been suggested to play a role in AD in both animal and human studies. Therefore, the microbiome gut-brain axis and the eCB system are potential common denominators in the AD physiopathology. Hence, the aim of this review is to provide a general overview on the role of both the eCB system and the microbiome gut-brain axis in AD and to suggest possible mechanisms that underlie the potential interplay of these two systems.
Keywords: endocannabinoid system; microbiota; Alzheimer’s disease; gut-brain axis
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Conclusions
Although both the eCB system and the gut microbiota have individually emerged as molecular targets in the pathology of AD as they may counteract inflammatory, neurodegenerative and cognitive aspects of the disease, research on the complex interactions of these systems in AD is still missing.
The overlapping roles of the eCB system and the microbiome in many diseases including dysmetabolism, obesity and neuropsychiatric disorders [19,44] suggest that a novel approach such as modulating the microbiota via eCB system may provide new therapeutic perspectives for treating AD. In particular, therapeutic strategies derived by diets or prebiotic and probiotic supplementation that might promote and support the growth of bacteria synthetizing beneficial mediators, eCBs and eCB-like compounds included, acting as AD-modifying drugs should be examined. On the other hand, the potential beneficial role of increased levels of 2-AG and hence the activation of CB2 and other molecular targets belonging to the family of eCBome receptors mediating inflammation and gut microbiota composition and diversity should be clarified.
In conclusion, studies are now needed to provide answers to the question of whether or not the eCB system can be considered a bridge between gut microbiota and AD to be target for the development of applicable interventions for the treatment of the progress of neurodegenerative disorders.
 
Johannes W. Dietrich
added a research item
Feedback loops are among the primary network motifs in living organisms, ensuring survival via homeostatic control of key metabolites and physical properties. However, from a scientific perspective, their characterization is unsatisfactory since the usual modelling methodology is incompatible with the physiological and biochemical basis of metabolic networks. Therefore, any "vertical translation", i.e. the study of the correspondence between molecular and organismal levels of causality, is difficult and in most cases impossible. As a viable solution, we demonstrate an alternative modelling platform for biological feedback loops that is based on key biochemical principles, including mass action law, enzyme kinetics, binding of mediators to transporters and receptors, and basic pharmacological properties. Subsequently, we show how this framework can be used for translating from molecular to systems-level behaviour. Basic elements of the proposed modelling platform include Michaelis-Menten kinetics defining nonlinear dependence of the output y(t) on an input signal x(t) with the Hill-Langmuir equation y(t) = G * x(t) n / (D + x(t) n), non-competitive inhibition for linking stimulatory and inhibitory inputs with y(t) = G + x1(t) / ((D + x1(t) * (1 + x2(t) / KI)) and processing structures for distribution and elimination. Depending on the structure of the feedback loop, its equifinal (steady-state) behaviour can be solved in form of polynomials, with a quadratic equation for the simplest case with one feedback loop and a Hill exponent of 1, and higher-grade polynomials for additional feedback loops and/or integer Hill exponents > 1. As a companion to the analytical solution, a flexible class library (CyberUnits) facilitates computer simulations for studying the transitional behaviour of the feedback loop. Unlike other modelling strategies in biocybernetics and systems biology, this platform allows for straightforward translation from the statistical properties of single molecules on a "microscopic" level to the behaviour of the whole feedback loop on an organismal "macroscopic" level. An example is the Michaelis constant D, which is equivalent to (k-1 + k2) / k1, where k1, k-1 and k2 denote the rate constants for the association and dissociation of the enzyme-substrate or receptor-hormone complex, respectively. From the perspective of a single molecule the rate constants represent the probability (per unit time) that the corresponding reaction will happen in the subsequent time interval. Therefore 1/k represents the mean lifetime of the complex. Very similar considerations apply to the other described constants of the feedback loop. In summary, this modelling technique renders the translation from a molecular level to a systems perspective possible. In addition to providing new insights into the physiology of biological feedback loops, it may be a valuable tool for multiple disciplines of biomedical research, including drug design, molecular genetics and investigations on the effects of endocrine disruptors. PHYSICAL CHEMISTRY 2021 D-05-S 216 INTRODUCTION In life sciences, the function of organisms uses to be described on several and distinct levels of causality, ranging from the behaviour of single elementary particles to the performance of whole living creatures and even social interactions. While approaches remaining on one level only are able to successfully provide physiological insights and while they are usable for practical purposes, including clinical reasoning and epidemiological decision making, the translation between the levels of causality is difficult and, in most cases, virtually impossible [1]. A methodology bridging this gap is highly needed, but previous approaches were unsatisfactory [2]. An example of this dilemma that is both typical and significant is feedback control systems. Feedback loops are fundamental network motifs and information processing structures in living organisms, providing means for homeostatic control of vital parameters including the concentration of key metabolites and important physical properties. Unfortunately, the usual methodology for the mathematical description of feedback loops as linear time-invariant (LTI) systems is not readily compatible with biochemical insights and theories [2]. It is, therefore, impossible to draw conclusions from physicochemical processes to the corresponding response of the organism and vice versa. Here, we suggest an alternative modelling platform for systems biology that is able to establish compatibility between the distinct levels of causal description, thereby providing a framework for vertical translation between molecular and organismal levels of interaction. Additionally, we demonstrate how this framework can be exploited to translate between different levels of causality.
Jiří Kroc
added an update
Yucheng Guo, Pixiang Qiu & Taoguang Liu
Journal of Sport and Health Science 3:1 (March 2014) 3-8
DOI: 10.1016/j.jshs.2013.10.004
Abstract
Tai Ji Quan is considered to be a part of traditional Chinese Wushu (a martial art) and comprises various styles that have evolved historically from the Chen, Yang, Wǔ,Wu´, and Sun families (schools). Recent simplification of the original classic styles has made Tai Ji Quan easier to adopt in practice. Thus, the traditional legacy of using Tai Ji Quan for self-defense, mindful nurturing of well-being, and fitness enhancement has been expanded to more contemporary applications that focus on promoting physical and mental health, enhancing general well-being, preventing chronic diseases, and being an effective clinical intervention for diverse medical conditions. As the impact of Tai Ji Quan on physical performance and health continues to grow, there is a need to better understand its historical impact and current status. This paper provides an overview of the evolution of Tai Ji Quan in China, its functional utility, and the scientific evidence of its health benefits, as well as how it has been a vehicle for enhancing cultural understanding and exchanging between East and West.
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Conclusion
From its classic status as a martial art in ancient times to its diverse applications in the modern era, Tai Ji Quan has undergone a continual process of evolution, refinement, integration, and standardization. With increased recognition of its historical value and health-enhancing potential, Tai Ji Quan is making contributions in the areas of performance, biomedical research, and community health promotion through contemporary applications. Tai Ji Quan has clear potential to build on its existing reputation for optimizing and enriching human health and well-being.
 
Jiří Kroc
added an update
American Journal of Translational Research 10(11):3330-3344 (2018)
Jie  Xiao, Zhao  Peng, Yuxiao  Liao, Hui Sun, Weiqiang Chen, Xing Chen, Zhanjie  Wei, Chuanlei Yang, Andreas K Nüssler, Jinping Liu & Wei Yang
Abstract:  Organ  transplantation  is  often  the  only  effective  treatment  for  patients  with end-stage  diseases,  such  as heart, liver, kidney and small bowel failure  and is  carried  out  frequently  worldwide.  Still  the  post-transplantation complications remain  health-  and  life-threatening outcome  that  needed  to be resolved.  With the  rapid development  of  molecular  technologies  in recent  years, more  and  more  researchers realize  that  the  gut  microbiota  may play a critical role  in human  diseases.  The intestinal  microbiome  has been  proved  to  provide a lot  of  functions to the host, such  as digesting food,  modulating  metabolism,  promoting angiogenesis  and  regulating  the  immune system. Several  studies  have investigated  the  alteration  of intestinal  microbiota in  post-transplantation  patients and  observed  significant  changes  in  the  intestinal  microbiome  compared  to  the  pre-transplant  condition.  Due  to the  abovementioned  features  that  the  gut  microbiota  may be  used  in the  prognosis  of  clinical outcome  of  organ transplantation.  In addition,  the  FMT  (fecal  microbiota transplantation),  probiotics and prebiotics as the newest therapy  methods,  effectiveness  of  which  has  been  verified  in  some  diseases,  such  as  Clostridium  difficile  infection, inflammatory  bowel  disease  and  other  chronic  disorders,  might  be  used  as  the  prognosis  tool  in  organ  transplantation  as  well.  The  purpose  of  this present  review is to  elucidate  the  relationship  between  gut  microbiota  and  organ transplantation  as well as the  potential use  of  new therapies  like fecal  microbiota transplantation,  probiotic and prebiotic  administration  after  the  transplantation,  and  provide  some  ideas  for  future  researches  in  field  of  organ transplantation.
Keywords:  Organ transplantation, gut microbiota, complication, prognosis, fecal microbiota transplantation, probiotic, prebiotic
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Potential views and future challenges
Difference in gender, ethnicity, and age
As we all know, the composition of the intestinal  microbiota  differs  from  person  to  person [4], and  might  be  dependent  on gender  and  ethnicity as well. To  date, some  researchers  investigated  the  difference  between gut  microbiota  of  males  and females  [82-88]. Yurkovetskiy and  his  teammates [83] established  a  mice  model to  analysis the relationship of gender bias and intestinal microbiota.
 
Jiří Kroc
added an update
Duried Alwazeer, Franky Fuh-Ching Liu, Xiao Yu Wu & Tyler W. LeBaron
Oxidative Medicine and Cellular Longevity Volume 2021, Article ID 5513868, 17 pages, DOI: 10.1155/2021/5513868
Abstract:
COVID-19 is a widespread global pandemic with nearly 185 million confirmed cases and about four million deaths. It is caused by an infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which primarily affects the alveolar type II pneumocytes. The infection induces pathological responses including increased inflammation, oxidative stress, and apoptosis. This situation results in impaired gas exchange, hypoxia, and other sequelae that lead to multisystem organ failure and death. As summarized in this article, many interventions and therapeutics have been proposed and investigated to combat the viral infection-induced inflammation and oxidative stress that contributes to the etiology and pathogenesis of COVID-19. However, these methods have not significantly improved treatment outcomes. This may partly be attributable to their inability at restoring redox and inflammatory homeostasis, for which molecular hydrogen (H2), an emerging novel medical gas, may complement. Herein, we systematically review the antioxidative, anti-inflammatory, and antiapoptotic mechanisms of H2. Its small molecular size and nonpolarity allow H2 to rapidly diffuse through cell membranes and penetrate cellular organelles. H2 has been demonstrated to suppress NF-κBinflammatory signaling and induce the Nrf2/Keap1 antioxidant pathway, as well as to improve mitochondrial function and enhance cellular bioenergetics. Many preclinical and clinical studies have demonstrated the beneficial effects of H2 in varying diseases, including COVID-19. However, the exact mechanisms, primary modes of action, and its true clinical effects remain to be delineated and verified. Accordingly, additional mechanistic and clinical research into this novel medical gas to combat COVID-19 complications is warranted.
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An explanation for the advantageous effects of molecular hydrogen in COVID-19 treatment is related to the different properties of molecular hydrogen: (1) the small molecular size and nonpolarity of H2 allow it to rapidly permeate the tissues and cells, (2) it can selectively reduce only the cytotoxic ROS, (3) it can suppress the excessive production of otherwise good ROS, (4) it can suppress proinflammatory cytokines, (5) it can induce cytoprotective heat shock proteins, (6) it can improve mitochondrial bioenergetics, and (7) it has no known toxic effects even at very high levels [114]. These properties may explain the improvement in the conditions of COVID-19 patients treated by inhalation of H2/O2 mixed gas (67% H2/33% O2), who felt reduction in chest pain and cough, and easier deeper breathing and comfortsensation[62,63].
...
Owing to the widespread transmissibility and emergence of more infectious variants of SARS-CoV-2, many hospitals have been overwhelmed by the crush of new COVID-19 patients and have exhausted ICU beds and ventilators in some regions. Therefore, an alternative yet effective treatment, e.g., H2/O2 gas inhalation, would ease the pressure on hospitals and prevent severe illness of COVID-19 patients. The medical model of H2/O2 mixed gas machine is small, portable, and safe [119]. It costs about one-tenth of the price of a ventilator. The H2/O2 inhalation treatment may be performed in regular wards or by outpatients at home isolation using a portable H2/O2 generating and inhalation device.
...
 
Jiří Kroc
added an update
Fan-Yun Lan, Amalia Sidossis, Eirini Iliaki, Jane Buley, Neetha Nathan, Lou Ann Bruno-Murtha, & Stefanos N. Kales
Preprint on medRxive
Important note: No single reinfection by COVID-19 variants observed among all previously infected healthcare workers! Infection by COVID-19 gave participants of the study a very solid immunity to all subsequent strains!
Abstract
Background Data on COVID-19 vaccine effectiveness (VE) among healthcare workers (HCWs) during periods of delta variant predominance are limited.
Methods We followed a population of urban Massachusetts HCWs (45% non-White) subject to epidemiologic surveillance. We accounted for covariates such as demographics and community background infection incidence, as well as information bias regarding COVID-19 diagnosis and vaccination status.
Results and Discussion During the study period (December 16, 2020 to September 30, 2021), 4615 HCWs contributed to a total of 1,152,486 person-days at risk (excluding 309 HCWs with prior infection) and had a COVID-19 incidence rate of 5.2/10,000 (114 infections out of 219,842 person-days) for unvaccinated person-days and 0.6/10,000 (49 infections out of 830,084 person-days) for fully vaccinated person-days, resulting in an adjusted VE of 82.3% (95% CI: 75.1–87.4%). For the secondary analysis limited to the period of delta variant predominance in Massachusetts (i.e., July 1 to September 30, 2021), we observed an adjusted VE of 76.5% (95% CI: 40.9–90.6%). Independently, we found no re-infection among those with prior COVID-19, contributing to 74,557 re-infection-free person-days, adding to the evidence base for the robustness of naturally acquired immunity.
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Please, share this very important and unexpected observation in this study among all interested, healthcare providers, and decision makers on all levels. It can substantially decrease the amount of stress among  healthcare providers acting at the frontline!
 
Jiří Kroc
added an update
Alina  Yuryevna  Maslova, Kheda  Lechaevna  Bazaeva,   Zaira  Arazovna  Abdullaeva,  Shuainat  Omarovna Khazamova,   Karina  Akhmedovna  Zeusheva,  Tatiana  Alekseevna  Grechkina,   Evgeniya  Nikolaevna  Semkina, Maksim  Alekseevich  Abramov,   Artem  Evgenevich  Mishvelov  and Sergey Nikolaevich Povetkin
Abstract
At present, research in the field of the brain does not cease to surprise us with new facts and discoveries that no one could have suspected about 30 years ago. But it was at the time when it became clear that the cerebral neurons are not the only cells that can respond to changes in the external environment. A real scientific boom began to study a heterogeneous group called glia. And scientists are paying close attention to the largest of them – astrocytes. Understanding the importance of astrocytes in the mechanisms of repair and damage to brain cells in various forms of CNS pathology determines the possibility of targeted search for drugs that affect the rate of development of reactive astrogliosis in response to various brain injuries. At the same time, pharmacological modulation of activated astrocytes and other components of glia can be an integral part of the therapy of neurological diseases.
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A fascinating area of research that brings us closer to ultimate understanding of brain functioning and its relationship to consciousness.
Those interested about this research are welcomed to read more at:
 
Jiří Kroc
added an update
Virginie Lam, Andrea Stephenson, Michael Nesbit, Somayra Mamsa, Mark Hackett, Ryusuke Takechi and John C L Mamo
Nutritional Neuroscience 24(1):1-9 (September 2019)
DOI: 10.1080/1028415X.2019.1664533
Abstract
Background: A body of epidemiological, clinical and preclinical studies suggest increased risk for cerebro- and cardio-vascular disease associated with dietary ingestion of long-chain saturated fatty acids (LCSFA). In wild-type rodent models, chronic ingestion of LCSFA diets are associated with increased cerebral capillary permeability, heightened neurovascular inflammation and poorer cognitive performance. However, recent studies suggest that diets enriched in fat may paradoxically attenuate elements of the ageing phenotype via a caloric support axis. Objective: The purpose of this study was to explore the effects of dietary LCSFA on cerebral capillary integrity and neurovascular inflammation in an established model of accelerated ageing, Senescence-Accelerated-Murine-Prone Strain 8 (SAMP8) mice. Methods: From 6 weeks of age, SAMP8 mice and age-matched controls were randomised to either normal chow, or to an LCSFA-enriched diet, for either 12 or 34 weeks. An additional group of SAMP8 mice were provided the LCSFA-enriched diet for 12 weeks followed by the provision of ordinary low-fat chow for 22 weeks. Ex vivo measures of cerebrovascular integrity, neurovascular inflammation and astrocytic activation, were determined via 3-dimensional immunofluorescent confocal microscopy methodologies. Results: LCSFA-fed SAMP8 mice had markedly attenuated cerebral capillary dysfunction concomitant with reduced microglial activation. In SAMP8 mice transiently maintained on an LCSFA diet for 12 weeks, suppression of neurovascular inflammation persisted. Marked hippocampal astrogliosis was evident in LCSFA-fed mice when compared to SAMP8 mice maintained on ordinary chow. Conclusion: The findings from this study support the notion that high-fat, potentially ketogenic diets, may confer neuroprotection in SAMP8 mice through a vascular-support axis.
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From the Discussion:
... "Paradoxical findings are hereby reported whereby chronic ingestion of an LCSFA-enriched diet not only substantially attenuated cerebrovascular dysfunction in aged SAMP8 mice, but a significant reduction in microglial activity was evident, potentiating the role of high-fat diets in the restoration of cerebrovascular perturbations in ageing." ...
"The observations in SAMP8 mice on normal chow are consistent with f indings in genetically modified murine models of dementia [40,41]. However, in contrast to wild-type genetically un-manipulated mice maintained on LCSFA diet concomitant with marked capillary leakage, SAMP8mice maintained on an LCSFA dietary intervention for 12 weeks showed marked attenuation of cerebral capillary permeability, strongly indicative of a vasculoprotective effect of the modified feeding regime. The dietary formulation of chow previously reported in wild-type mice [16,42] and now in this study, are exactly the same and provided by the same accredited provider. The vascuoloprotective effects of the feeding regime were further supported by the significant attenuation of IgG brain parenchymal extravasation in SAMP8 mice maintained on the LCSFAdiet anadditional 22 weeks (LCSFA fed for a duration of 34 weeks), when compared to their respective 40-week SAMP8 controls. Moreover, SAMP8 mice fed a LCSFA-regime for 12 weeks followed by conversion to 22 weeks of control chow as a ‘rescue’ intervention, indicated persistent positive modulation of the capillary index." ...
 
Jiří Kroc
added an update
Kinga Kowalska-Duplaga, Tomasz Gosiewski, Przemysław Kapusta, Agnieszka Sroka-Oleksiak, Andrzej Wędrychowicz, Stanisław Pieczarkowski, Agnieszka H. Ludwig-Słomczyńska, Paweł P. Wołkow & Krzysztof Fyderek
Scientific Reports 9 (2019) 18880
Abstract
The aetiology of inflammatory bowel diseases (IBD) seems to be strongly connected to changes in the enteral microbiome. The dysbiosis pattern seen in Crohn’s disease (CD) differs among published studies depending on patients’ age, disease phenotype and microbiome research methods. The aims was to investigate microbiome in treatment-naive paediatric patients to get an insight into its structure at the early stage of the disease in comparison to healthy. Stool samples were obtained from controls and newly diagnosed patients prior to any intervention. Microbiota was analysed by 16SrRNAnext-generation-sequencing (NGS). Differences in the within-sample phylotype richness and evenness (alpha diversity) were detected between controls and patients. Statistically significant dissimilarities between samples were present for all used metrics. We also found a significant increase in the abundance of OTUs of the Enterococcus genus and reduction in, among others, Bifidobacterium (B. adolescentis), Roseburia (R.faecis), Faecalibacterium (F. prausnitzii), Gemmiger (G. formicilis), Ruminococcus (R. bromii) and Veillonellaceae (Dialister). Moreover, differences in alpha and beta diversities in respect to calprotectin and PCDAI were observed: patients with calprotectin <100 µg/g and with PCDAI below 10 points vs those with calprotectin >100 µg/g and mild (10–27.7 points), moderate (27.5–40 points) or severe (>40 points) CD disease activity had higher richness and diversity of gut microbiota. The results of our study highlight reduced diversity and dysbiosis at the earliest stage of the disease. Microbial imbalance and low abundance of butyrate-producing bacteria, including Bifidobacterium adolescentis, may suggest benefits of microbial modification therapy.
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Conclusions:
Our work contributes to the data helping understand intestinal dysbiosis in new-onset, treatment-naive paediatric CD patients.
If the change in intestinal microflora is one of the risk factors for the development and / or persistence of inflammation in IBD, then the microbiome-oriented treatment should be a component of the therapeutic goals. Such treatment methods as antibiotics, pro- and prebiotics as well as faecal microbiota transplant can be taken into account. Furthermore, considering the relationship between microbiota and genetic predisposition, the usefulness of a microbiome-based preventive treatment in high-risk groups may be considered.
Consistent data confirming low abundance and diversity of Bifidobacterium in CD patients suggest that further studies are needed to answer the question whether it is possible to use Bifidobacterium adolescentis as a probiotic.
Although studies of the faecal stream may face limitations in detecting microbes associated with the mucus layer and, thus, those more directly involved in disease initiation and perpetuation, the application of this method is far less invasive and allows multiple and reproducible material collection which makes it possible to monitor disease progression.
It is still an open field and active research area for investigation of the best therapeutic strategies to successfully manipulate microbiota in CD patients.
 
Jiří Kroc
added an update
Joakim Sundnes
Python is a very useful tool in prototyping of software tools, and which can be used in many cases even as the final software product. Python has a huge set of modules enabling literally everyone to start to program quickly and efficiently. Everyone who want to learn Python from the scratch will definitely benefit from this extraordinary introduction into scientific computing in Python book!
Open access book link an more details available to everyone here:
 
Jiří Kroc
added an update
Ching Lan, Ssu-Yuan Chen, May-Kuen Wong, and Jin Shin Lai
Review Article | Open Access
Evidence-Based Complementary and Alternative Medicine (2013) ID 983208, 9 pages
Abstract
Exercise training is the cornerstone of rehabilitation for patients with cardiovascular disease (CVD). Although high-intensity exercise has significant cardiovascular benefits, light-to-moderate intensity aerobic exercise also offers health benefits. With lower-intensity workouts, patients may be able to exercise for longer periods of time and increase the acceptance of exercise, particularly in unfit and elderly patients. Tai Chi Chuan (Tai Chi) is a traditional Chinese mind-body exercise. The exercise intensity of Tai Chi is light to moderate, depending on its training style, posture, and duration. Previous research has shown that Tai Chi enhances aerobic capacity, muscular strength, balance, and psychological well-being. Additionally, Tai Chi training has significant benefits for common cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, poor exercise capacity, endothelial dysfunction, and depression. Tai Chi is safe and effective in patients with acute myocardial infarction (AMI), coronary artery bypass grafting (CABG) surgery, congestive heart failure (HF), and stroke. In conclusion, Tai Chi has significant benefits to patients with cardiovascular disease, and it may be prescribed as an alternative exercise program for selected patients with CVD.
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Conclusion from the paper:
"Tai Chi exercise may promote cardiovascular health and can be considered as an alternative exercise program for patients with CVD. Previous studies prove that Tai Chi is safe and effective for patients with acute myocardial infarction, coronary artery bypass grafting surgery, congestive heart failure, and stroke. In addition, Tai Chi has benefits to cardiovascular risk factors, such as hypertension, diabetes, dyslipidemia, poor exercise capacity, endothelial dysfunction, and depression. However, the study design and training protocols among Tai Chi studies vary significantly, and hence the results are difficult to compare. In future research, large-scale randomized controlled trials using standardized training protocols should be performed in accordance with the guidelines of exercise prescription for patients with cardiovascular disease." 
 
Jiří Kroc
added an update
Andrew Adamatzky
All biology process information in one or the other way. It is of great value to be aware of the means of biocomputing.
From the Discussion of the paper:
Several contributions to this special issue have demonstrate that a creature does not need a nervous system, in its classical sense, to fuse sensorial inputs, process information and make a decision. The most exciting examples include learning by the slime mould, morphogenetic positional computing, distributed information processing in plant organs, and neuronal-like activity of bacterial biofilms. In the present paper, I show that a substrate does not need to be alive or posses any particular electrical or biochemical properties to compute: even a liquid, which you would be unable to keep in your hands, can perform sophisticated computing circuits.
Those interested more about this exciting topic are welcomed to follow the link and read the whole review:
 
Jiří Kroc
added an update
Aman Mahajan, Saleh Saleh, Julien I.E.Hoffman, Cecil Coghlan
The Journal of Thoracic and Cardiovascular Surgery 136 (3):78-589.e11 (September 2008)
DOI: 10.1016/j.jtcvs.2007.10.088
Abstract:
Objective
Understanding cardiac function requires knowledge of the architecture responsible for the normal actions of emptying and filling. Newer imaging methods are surveyed to characterize directional (narrowing, shortening, lengthening, and widening) and twisting motions.
Methods
These movements are defined and then compared with a spectrum of models to introduce a useful “functional anatomy” that explains cardiac spatial and temporal relationships. The sequential nature of normal contraction differs from a synchronous beat.
Results
The prior concept of constriction is replaced by understanding that clockwise and counterclockwise helical motions are necessary to cause the predominant twisting motion. The helical ventricular myocardial band model of Torrent-Guasp fulfills the architectural structure to define normal function. Expansion of information from this model allows novel understanding of mechanisms that explains why a component of ventricular suction involves a systolic event, clarifies septum function, determines diastolic dysfunction, introduces new treatments, shows how knowledge of the helical structure influences understanding of atrioventricular and biventricular pacing, and creates novel methods for introducing septal pacing stimuli.
Conclusion
Further testing of these spatial anatomic concepts is needed to create a more accurate understanding of the architectural mechanisms that underlie cardiac dynamics to address future problems in unhealthy hearts.
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Conclusions
The architectural background for standard observations of heart function were compared with several structural models. The resultant findings were most consistent with the HVMB model of Torrent-Guasp, whose dissection pattern confirms the conceptual classic figure of 8 configuration described by the forefathers of anatomy and demonstrates functional preferential pathways that explain the observed directional and twisting sequential motions.
Application of this information allowed a unified concept of form to introduce rethinking of the mechanical factors causing the normal dynamic actions of normal hearts; showed differences between synchronous versus sequential beats; demonstrated that a muscular syncytium does not exist during systole in the heart; explained the fiber orientation and function of the septum; identified that “isovolumic diastolic relaxation” is an incorrect term; defined muscular reasons for ventricular suction and showed how novel treatments may relieve this event in the stunned heart; demonstrated the structure/function limitations of synchronous univentricular and biventricular pacing; and introduced a septum pacing concept producing sequential shortening that may have subsequent clinical application.
Further testing of these spatial anatomic concepts is needed, because the architectural coordination of structure and function, if properly confirmed, may answer in part Keith's challenge during his Harvian Lecture in 1918, when he inquired, “How far does our knowledge of the function of the mammalian heart fall short of explaining its structure?” The natural concept of balance should apply to ventricular emptying and filling. Einstein indicated that “gravity and acceleration are equivalent,” and Da Vinci stated that “heart blood is like tides; pulses are ebb and flow of ocean.” Consequently, cardiac ejection and rapid filling should not be different. 
 
Jiří Kroc
added an update
Peilin Zheng, Zhixia Li & Zhiguang Zhou
Diabetes/Metabolism Research and Reviews 34(7): e3043 (21 June 2018)
DOI: 10.1002/dmrr.3043
Summary
Type 1 diabetes (T1D) is an autoimmune disease, which is characterized by the destruction of islet β cells in the pancreas triggered by genetic and environmental factors. In past decades, extensive familial and genome-wide association studies have revealed more than 50 risk loci in the genome. However, genetic susceptibility cannot explain the increased incidence of T1D worldwide, which is very likely attributed by the growing impact of environmental factors, especially gut microbiome. Recently, the role of gut microbiome in the pathogenesis of T1D has been uncovered by the increasing evidence from both human subjects and animal models, strongly indicating that gut microbiome might be a pivotal hub of T1D-triggering factors, especially environmental factors. In this review, we summarize the current aetiological and mechanism studies of gut microbiome in T1D. A better understanding of the role of gut microbiome in T1D may provide us with powerful prognostic and therapeutic tools in the near future.
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From the "CONCLUSION AND PERSPECTIVE":
"To sum up, T1D is an autoimmune disease triggered by both genetic and environmental factors. In past decades, a substantial progression has been made to clarify the genetics risk factors by using genome-wide association studies. But genetics alone is not sufficient to explain why the prevalence of T1D increases at a rate of 3% to 5% per year, when considering genetics in population to be relatively stable. In recent years, the importance of environmental factors in T1D, especially gut microbiome, has been realized. Growing attention has been paid to clarify the taxonomic and functional changes of gut microbiome in the disease pathogenesis, and the interplay between gut microbiome with immune system, which is becoming the hotspot of both research and clinical trials in the field."
"Gut microbiome, especially SCFAs, are important to maintain intestinal barrier and immune homeostasis. Evidence so far has demonstrated that dysbiosis of gut microbiome increases T1D predisposition. In humans or animals, the decreased diversity of gut microbiome occurs before disease onset and remains after the diagnosis of T1D. Bacteroidetes and Firmicutes are dominant in the faecal samples. The ratio of Firmicutes to Bacteroidetes is decreased in T1D patients. Dialister invisus, Gemella sanguinis, and Bifidobacterium longum are associated with intestinal permeability. Once the balance of gut microflora is disrupted, the compromised intestinal mucosa permeability may lead to outer or bacterial antigen leakage, boosting excessive immune response or activating autoreactive T cells by molecular mimicry (Figure 1)."
 
Oleksandr P. Romanchuk
added a research item
The purpose of the study was a comparative analysis of sensorimotor reactions in highly trained athletes with different types of heart rate regulation. Materials and methods. 202 highly trained male athletes aged 22.6±2.8 years, who are engaged in acyclic sports – martial arts (karate, taekwondo, kickboxing, boxing, freestyle wrestling, Greco-Roman wrestling, judo, sambo) and games (water polo, soccer) were examined. The experience in sports was 10.3±3.1 years. All studies were conducted in the pre-competition period in the morning. Based on the study of heart rate variability in athletes, the type of heart rate regulation was determined. The basis for determining the types of regulation is the classification of heart rate variability indicators, taking into account their inclusion in certain limits. Heart rate variability indicators that reflect the dual-circuit model of heart rate regulation and are used for diagnosis include: total heart rate variability – total power (ms2), very low frequency (ms2), and stress-index (e.u.), which reflect the various chains of regulatory effects on heart rate. According to certain data types, 4 groups were formed. 1 group (type I) consisted of 42 athletes, 2 (type II) – 28 athletes, 3 (type III) – 88 athletes, 4 (type IV) – 44 athletes. The study of sensorimotor function was performed using the device KMM-3. Results and discussion. It is shown that the most balanced sensorimotor reactions are in athletes with type III regulation of heart rate. The most strain sensorimotor reactions are observed in type II regulation of heart rate, which is reflected in the pronounced central asymmetry of movement control with acceleration to the left against the background of deteriorating accuracy of right (due to flexors) and left (due to extensors) limbs, and the right-hand predominance. Sensorimotor reactions are quite strain in type IV of heart rate regulation, which is characterized by slow reactions at the synaptic and peripheral levels. In type I of heart rate regulation, the disorders observed at the central level of regulation relate to the asymmetry of short-term motor memory processes, which are significantly reduced in the left hemisphere. Conclusion. The study shows that the differences in the regulatory support of heart rate in highly qualified athletes are accompanied by characteristic differences in sensorimotor function. The latter can be useful for the diagnosis and further correction of conditions associated with the development of overexertion and overtraining. Keywords: types of autonomous regulation, heart rate, sensorimotor reactions, athletes.
Jiří Kroc
added an update
Jiří Kroc
Software License: CC BY-NC-SA 4.0
Description
This program serves as an introduction into complex systems modeling. The GoL was developed by John Conway in the 70ies, and it gained a huge attention by both researchers and mathematical enthusiasts. In the past, such programs designed in some higher-level programming language can easily exceed thousands of code lines. This program has about one hundred lines within which defines updating rules, visualize the lattice, and even save the animation. Everyone who is starting to model and understand complex systems modeling will benefit from the simplicity and clarity of the program. The code contains many comments in order to enable newcomers to follow in detail all its functions and to modify them according to their own preferences and needs. The chosen approach allows non-specialists along with all those who just want to passively understand the methodology to dive into this non-sequential way of thinking quite easily. The way of cellular automata modeling is very tightly related to massively parallel thinking, which is a bit tricky to newcomers. All what must be understood about those models is that the surrounding world (CA lattice) is observed and interacted with from each cell independently. This means that the rule of thumb of all CA modeling is to update all variables within the updated cell centripetally, and do not change any values outside it. Another important feature of CA modeling is the necessity to work with the old and new layers of the updated lattice, which are periodically switched. This allows us to overcome the unsolvable problem of the sequential updating of all cells within just one lattice, when it would be used instead. In such case, cells would be updated sequentially, one-by-one: cells containing new and old data will become mixed up in the same lattice. This is really something that we do not want to have in any CA model in the first place. Each initial configuration must be inserted into the Python program manually within its beginning: coordinates defines the live cells having the value equal to one. Complicated configurations can be quite difficult to insert because the loading of the initial configuration into the program was sacrificed due to the extra effort to keep it simple and easy to understand. Literature and all necessary programming resources are listed in the README file. This program is designed as the methodical one. It should be cited along with one of the recommended papers provided in the README file.
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Massively parallel mathematical descriptions are creating the fundamental piece of the puzzle called systemic biology and medicine. For example, gut microbiota found in human gut has incredible complexity on its own and even greater in interactions with our own cells.
This is why we must try to understand, adopt, and explore usefulness of complex systems descriptions of living entities: going from viruses, bacteria, across our cells, tissues, organs, and ending with bodies & ecosystems.
The best way to initiate studies of massively parallel information processing environments is to explore the existence, creation, and functions of emergents: structures that are arising through interactions of large numbers of simple parts of the system.
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Read more about and download the Python3 software:
 
Jiří Kroc
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Dae-Wook Kang, James B. Adams, Troy Vargason, Marina Santiago, Juergen Hahn, and Rosa Krajmalnik-Brown
mSphere 5:5 (Oct 2020) e00314-20
DOI: 10.1128/mSphere.00314-20
Abstract:
"Accumulating evidence has strengthened a link between dysbiotic gut microbiota and autism. Fecal microbiota transplant (FMT) is a promising therapy to repair dysbiotic gut microbiota. We previously performed intensive FMT called microbiota transfer therapy (MTT) for children with autism spectrum disorders (ASD) and observed a substantial improvement of gastrointestinal and behavioral symptoms. We also reported modulation of the gut microbiome toward a healthy one. In this study, we report comprehensive metabolite profiles from plasma and fecal samples of the children who participated in the MTT trial. With 619 plasma metabolites detected, we found that the autism group had distinctive metabolic profiles at baseline. Eight metabolites (nicotinamide riboside, IMP, iminodiacetate, methylsuccinate, galactonate, valylglycine, sarcosine, and leucylglycine) were significantly lower in the ASD group at baseline, while caprylate and heptanoate were significantly higher in the ASD group. MTT drove global shifts in plasma profiles across various metabolic features, including nicotinate/nicotinamide and purine metabolism. In contrast, for 669 fecal metabolites detected, when correcting for multiple hypotheses, no metabolite was significantly different at baseline. Although not statistically significant, p-cresol sulfate was relatively higher in the ASD group at baseline, and after MTT, the levels decreased and were similar to levels in typically developing (TD) controls. p-Cresol sulfate levels were inversely correlated with Desulfovibrio, suggesting a potential role of Desulfovibrio on p-cresol sulfate modulation. Further studies of metabolites in a larger ASD cohort, before and after MTT, are warranted, as well as clinical trials of other therapies to address the metabolic changes which MTT was not able to correct."
"IMPORTANCE Despite the prevalence of autism and its extensive impact on our society, no U.S. Food and Drug Administration-approved treatment is available for this complex neurobiological disorder. Based on mounting evidences that support a link between autism and the gut microbiome, we previously performed a pioneering open-label clinical trial using intensive fecal microbiota transplant. The therapy significantly improved gastrointestinal and behavioral symptoms. Comprehensive metabolomic measurements in this study showed that children with autism spectrum disorder (ASD) had different levels of many plasma metabolites at baseline compared to those in typically developing children. Microbiota transfer therapy (MTT) had a systemic effect, resulting in substantial changes in plasma metabolites, driving a number of metabolites to be more similar to those from typically developing children. Our results provide evidence that changes in metabolites are one mechanism of the gut-brain connection mediated by the gut microbiota and offer plausible clinical evidence for a promising autism treatment and biomarkers."
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From the text:
Conclusions.
"In summary, MTT drove global changes in plasma metabolite profiles in children with ASD. Vancomycin seems to initiate a shift in the plasma metabolite profiles, but microbiota transfer resulted in further shifts and seemed to stabilize the effect of vancomycin. As a result, plasma metabolite profiles in the ASD group were modulated from being distinctly different from those in the TD group to becoming similar to those in the TD group. Among plasma metabolites that were significantly different in ASD at baseline, medium-chain fatty acids (caprylate and heptanoate) were significantly higher at baseline than in the control and significantly decreased after MTT. Nicotinamide riboside, IMP, iminodiacetate, methylsuccinate, leucylglycine, and sarcosine were significantly lower at baseline and increased after MTT. Other metabolites such as galactonate and valylglycine were abnormal at baseline and did not improve after MTT, and so those are potential targets for other future therapies. Overall, these data provide some insight into why microbiota transplant therapy appears to be able to significantly reduce GI and ASD symptoms. It also suggests a biochemical basis for some ASD symptoms."
"In contrast, for fecal metabolites, only a few metabolites were different at baseline, and none were significantly different after correction for multiple-hypotheses testing. At baseline, p-cresol sulfate, 4-hydroxyphenylacetate, tyramine O-sulfate, and indole were relatively different between groups (unadjusted P < 0.05), and only p-cresol sulfate significantly changed toward that in the TD group after MTT. There were significant correlations between p-cresol sulfate, sulfate, and Desulfovibrio, suggesting a potential role of Desulfovibrio in the metabolism of p-cresol sulfate and possible autism etiology. Further studies of fecal and blood metabolites in ASD, before and after MTT, are warranted, as well as clinical trials of other therapies, to address the metabolic changes which MTT was not able to correct."
 
Jiří Kroc
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Cody Durrer, Sean McKelvey, Joel Singer, Alan M. Batterham, James D. Johnson, Kelsey Gudmundson, Jay Wortman & Jonathan P. Little
NATURE COMMUNICATIONS 12:5367 (2021) 1-8
DOI: 10.1038/s41467-021-25667-4
Abstract:
Type 2 diabetes can be treated, and sometimes reversed, with dietary interventions; however, strategies to implement these interventions while addressing medication changes are lacking. We conducted a 12-week pragmatic, community-based parallel-group randomized controlled trial (ClinicalTrials.gov: NCT03181165) evaluating the effect of a low-carbohydrate (<50 g), energy-restricted diet (~850-1100 kcal/day; Pharm-TCR; n = 98) compared to treatment-as usual (TAU; n = 90), delivered by community pharmacists, on glucose-lowering medication use, cardiometabolic health, and health-related quality of life. The Pharm-TCR intervention was effective in reducing the need for glucose-lowering medications through complete discontinuation of medications (35.7%; n = 35 vs. 0%; n = 0 in TAU; p < 0.0001) and reduced medication effect score compared to TAU. These reductions occurred concurrently with clinically meaningful improvements in hemoglobin A1C, anthropometrics, blood pressure, and triglycerides (all p < 0.0001). These data indicate community pharmacists are a viable and innovative option for implementing short-term nutritional interventions for people with type 2 diabetes, particularly when medication management is a safety concern.
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Selection from the 'Discussion' of the paper:
Discussion
"There is mounting evidence that type 2 diabetes can be reversed through nutritional interventions. What must be considered now is how people with type 2 diabetes can access efficacious interventions and how healthcare practitioners can safely deploy them. This study provides RCT level evidence that community-based pharmacists can effectively and safely implement a dietary intervention that rapidly reduces the need for glucose-lowering medications and improves cardiometabolic health in people with type 2 diabetes within a real-world setting."
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"A specific strength of this study was the use of pharmacists to deliver the nutritional intervention in the community. The need for rapid medication adjustments (i.e., within days/weeks to avoid predictable medication-related events) when following a low carbohydrate, low-calorie diet necessitates that someone knowledgeable in both type 2 diabetes and medication management has frequent and direct contact with participants. Given the risk of hypoglycemia and hypotension in this scenario, as well as the frequent visits that people with type 2 diabetes typically make to their local pharmacy 9, community pharmacists were uniquely positioned to fill this role. Although the intention was not for pharmacists to replace dietitians in delivering nutrition therapy, they were a suitable choice given the commercial weight loss plan that was selected to standardize the delivery of the nutritional intervention." 
 
Jiří Kroc
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Ghulam Yaseen
Annals of Clinical and Medical Case Reports 3: 1 (2020) 1-2
Abstract
Background: Acute Lymphoblastic Leukemia (ALL) is a cancer of lymphoid line of blood cells characterized by pallor complexion, progressive fatigue, easy bruising and bleeding, enlarged lymph nodes with bone pains. Incidents of ALL are growing globally with fatal results [1]. A demographic report published by United Nations showed that 53000 cases of ALL were recorded in 2016 world.
Case Presentation: A pre-diagnosed case of acute lymphoblastic leukemia of a 5 years old girl,presented in S.W.F. Homeopathic Clinic after getting chemotherapy with no cure. She had recurrent chest infection, her bone marrow with 20% of blast cells. Hemoglobin level 4.8g/dl, WBCs 2.3x103/l, RBCs 2.03 x106/l and PLTs were 89x 103/l considered as very low.
Conclusion: Report narrated highlights the potential effects of Homeopathic Medicines in the cure of Acute Lymphoblastic Leukemia.
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As the patient is considered a drug picture in homeopathy therefore no painful, costly or complicated tests are required. Homeopathy Physician still depends upon human skill such as using traditional means of investigation as they are trained for. On the other side dramatic change in science and technology revolutionized the medical treatment. Modern tools and test not only investigate the disease but also used as tools to gauge efficacy of a treatment. Presented case was primarily investigated according to typical homeopathic way and treated according to drug picture. Some clinical tests were done prior to homeopathic intervention and other tests after treatment, those tests were not desired by homeo physician but, parents for their personal satisfaction. However, Homeo physician used these tests just to report the case not to investigate or to prescribe any medicine.
 
Jiří Kroc
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Meng Zhou & Jiang Zhao
Frontiers in Molecular Biosciences (February 2021) 632955
DOI: 10.3389/fmolb.2021.632955
Abstract:
Due to their large number of applications, the pesticides pose potential toxicity risks to the non-target organisms. In recent years, the studies on the toxic effects of pesticides on non-target organisms, based on their gut microbiome and metabolome, have been continuously reported. As a dense and diverse microbial community, the gut microbiota in the mammalian gut plays a key role in the maintenance of host metabolic homeostasis. The imbalance in the gut microbiota of host is closely associated with the disturbance in the host's metabolic profile. A comprehensive analysis of the changes in the gut microbiota and metabolic profile of host will help in understanding the internal mechanism of pesticide-induced toxic effects. This study reviewed the composition and function of the gut microbiota of host, as well as the analysis methods and applications of metabolomics. Importantly, the latest research on the toxic effects of the exposure of pesticide to host was reviewed on the basis of changes in their gut microbiota and metabolic profile.
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From the paper:
Perspectives:
"In recent years, the gut microbiota of host has received more attention. Generally, the dysbiosis of gut microbiota often occurs simultaneously with the metabolic disorder of host. The studies on the health effects of host based on the changes in gut microbiota and metabolic profile have been continuously reported. In the past few decades, the pesticides have been widely used, and their toxic effects on the non-target organisms have received increasing attention. In particular, some studies have confirmed the destructive role of pesticides on the gut microbiota and metabolic profile of host. Unfortunately, most of these studies have only established a simple correlation between the pesticides and host gut microbiota and metabolic profile, while the key roles of the gut microbiota and metabolic profile host in the pesticide-induced toxic effects are still not focused. In particular, some studies have shown that some specific bacteria in gut microbiota can regulate specific metabolites or specific metabolic pathways, further affecting the host health. However, the current studies on the toxic effects of pesticides have not established a clear relationship between the specific pesticides and specific gut microbiota or metabolites. On the other hand, the key role of the gut microbiota and metabolic profile of host in the pesticide-induced toxic effect is needed to be further confirmed either by the transplantation of microbiota or the dietary supplementation of specific metabolites. In summary, this study reviewed the studies on the toxic effects of pesticides based on the gut microbiome and metabolomics of host. This review further emphasized on the role of changes in the gut microbiome and metabolomics of host in the pesticide-induced host toxic effects."
 
Jiří Kroc
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C. C. Wood
From the introduction if the paper:
"Computational biology (including bioinformatics) generally refers to the use of computational techniques in service of various branches of biological science, to ‘the understanding and modeling of the structures and processes of life’ (https://www.britannica.com/science/computational-biology) and to the ‘develop[ment of ] algorithms or models to understand biological systems and relationships (https://en.wikipedia.org/wiki/Computational_biology). Bioinformatics focuses on the development and application of large-scale databases of biological information, in particular databases in molecular biology where the approach developed with protein and genetic data [4]."
Those who want to read more are welcomed to follow the link:
 
Jiří Kroc
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Mitchell Liester
Medical Hypotheses 135(3):109468 (October 2019)
DOI: 10.1016/j.mehy.2019.109468
Abstract
Personality changes following heart transplantation, which have been reported for decades, include accounts of recipients acquiring the personality characteristics of their donor. Four categories of personality changes are discussed in this article: (1) changes in preferences, (2) alterations in emotions/temperament, (3) modifications of identity, and (4) memories from the donor's life. The acquisition of donor personality characteristics by recipients following heart transplantation is hypothesized to occur via the transfer of cellular memory, and four types of cellular memory are presented: (1) epigenetic memory, (2) DNA memory, (3) RNA memory, and (4) protein memory. Other possibilities, such as the transfer of memory via intracardiac neurological memory and energetic memory, are discussed as well. Implications for the future of heart transplantation are explored including the importance of reexamining our current definition of death, studying how the transfer of memories might affect the integration of a donated heart, determining whether memories can be transferred via the transplantation of other organs, and investigating which types of information can be transferred via heart transplantation. Further research is recommended.
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An excerpt from the paper:
The hypothesis
This article hypothesizes that cellular memory contributes to personality changes following heart transplantation surgery in which the recipient assumes personality traits of the donor. Memories from the donor’s life are hypothesized to be stored in the cells of the donated heart and are then “remembered” by the recipient following transplant surgery. Possible mechanisms by which memories may be stored are discussed including epigenetic memory, DNA memory, RNA memory, protein memory, intracardiac neurological memory, and energetic memory.
 
Jiří Kroc
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Peng Qiu, Yang Liu, & Jin Zhang
International Journal of Biological Sciences (2019) 15(6): 1261-1275
doi: 10.7150/ijbs.30741
Abstract:
Sepsis is a syndrome comprised of a series of life-threatening organ dysfunctions caused by a maladjusted body response to infection with no effective treatment. Molecular hydrogen is a new type of antioxidant with strong free radical scavenging ability, which has been demonstrated to be effective for treating various diseases, such as infection, trauma, poisoning, organ ischemia-reperfusion, metabolic diseases, and tumors. Molecular hydrogen exerts multiple biological effects involving anti-inflammation, anti-oxidation, anti-apoptosis, anti-shock, and autophagy regulation, which may attenuate the organ and barrier damage caused by sepsis. However, the underlying molecular mechanisms remain elusive, but are likely related to the signaling pathways involved. This review focuses on the research progress and potential mechanisms of molecular hydrogen against sepsis to provide a theoretical basis for clinical treatment.
Keywords: molecular hydrogen, sepsis, oxidative stress, apoptosis, shock, autophagy
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Conclusion and perspectives:
"In summary, molecular hydrogen exhibits multiple advantages in the treatment of sepsis due to its unique physicochemical properties. Molecular hydrogen scavenges free radicals selectively, modulates signaling transduction, and enters the nucleus to regulate transcription. Recent studies have shown that molecular hydrogen has a significant protective effect on multiple organs and physiological barriers in septic animal models. In addition to the well-known anti-oxidative stress effects, the mechanisms of molecular hydrogen against sepsis include anti-inflammation, anti-apoptosis, anti-shock and regulation of autophagy, each of which involves multiple signaling pathways and crosstalk. However, the potential molecular mechanisms are still not completely clear, and some results remain controversial, which need further research. Moreover, the current research results are mainly based on animal experiments. Whether these findings are equally applicable to humans is not yet known, which also requires further clinical studies to validate. Nevertheless, the advantages of molecular hydrogen have provided important means and optimistic prospects for treating sepsis."
 
Johannes W. Dietrich
added a research item
Feedback loops are among the primary network motifs in living organisms, ensuring survival via homeostatic control of key metabolites and physical properties. However, from a scientific perspective, their characterization is unsatisfactory since the usual modelling methodology is incompatible with the physiological and biochemical basis of metabolic networks. Therefore, any “vertical translation”, i.e. the study of the correspondence between molecular and organismal levels of causality, is difficult and in most cases impossible. As a viable solution, we demonstrate an alternative modelling platform for biological feedback loops that is based on key biochemical principles, including mass action law, enzyme kinetics, binding of mediators to transporters and receptors, and basic pharmacological properties. Subsequently, we show how this framework can be used for translating from molecular to systems-level behaviour. Basic elements of the proposed modelling platform include Michaelis-Menten kinetics defining nonlinear dependence of the output y(t) on an input signal x(t) with the Hill-Langmuir equation y ( t ) = G * x ( t ) n / ( D + x ( t ) n ), non-competitive inhibition for linking stimulatory and inhibitory inputs with y ( t ) = G + x 1 ( t ) / (( D + x 1 ( t ) * (1 + x 2 (t) / K I )) and processing structures for distribution and elimination. Depending on the structure of the feedback loop, its equifinal (steady-state) behaviour can be solved in form of polynomials, with a quadratic equation for the simplest case with one feedback loop and a Hill exponent of 1, and higher-grade polynomials for additional feedback loops and/or integer Hill exponents > 1. As a companion to the analytical solution, a flexible class library (CyberUnits) facilitates computer simulations for studying the transitional behaviour of the feedback loop. Unlike other modelling strategies in biocybernetics and systems biology, this platform allows for straightforward translation from the statistical properties of single molecules on a “microscopic” level to the behaviour of the whole feedback loop on an organismal “macroscopic” level. An example is the Michaelis constant D, which is equivalent to ( k –1 + k 2 ) / k 1 , where k 1 , k –1 and k 2 denote the rate constants for the association and dissociation of the enzyme-substrate or receptor-hormone complex, respectively. From the perspective of a single molecule the rate constants represent the probability (per unit time) that the corresponding reaction will happen in the subsequent time interval. Therefore 1/ k represents the mean lifetime of the complex. Very similar considerations apply to the other described constants of the feedback loop. In summary, this modelling technique renders the translation from a molecular level to a systems perspective possible. In addition to providing new insights into the physiology of biological feedback loops, it may be a valuable tool for multiple disciplines of biomedical research, including drug design, molecular genetics and investigations on the effects of endocrine disruptors.
Jiří Kroc
added an update
Paul Pearsall, Gary E. R. Schwartz & Linda G. S. Russek 
Integrative Medicine 2:2–3 (2000) 65-72
DOI: 10.1016/S1096-2190(00)00013-5
Abstract
Context: It is generally assumed that learning is restricted to neural and immune systems. However, the systemic memory hypothesis predicts that all dynamical systems that contain recurrent feedback loops store information and energy to various degrees. Sensitive transplant patients may evidence personal changes that parallel the history of their donors. Objective: To evaluate whether changes following heart transplant surgery parallel the history of the donors. Design: Open-ended interviews with volunteer (1) transplant recipients, (2) recipient families or friends, and (3) donor families or friends. Setting: Hospitals in various parts of the country. Patients: Ten recipients (7 males, 3 females; 7 months to 56 years old), received heart (or heart–lung) transplants (5 males, 5 females; 16 months to 34 years old). Main Outcome Measures: Transcripts of audio taped interviews quoted verbatim. Results: Two to 5 parallels per case were observed between changes following surgery and the histories of the donors. Parallels included changes in food, music, art, sexual, recreational, and career preferences, as well as specific instances of perceptions of names and sensory experiences related to the donors (e.g., one donor was killed by a gun shot to the face; the recipient had dreams of seeing hot flashes of light in his face). Conclusion: The incidence of recipient awareness of personal changes in cardiac transplant patients is unknown. The effects of the immunosuppressant drugs, stress of the surgery, and statistical coincidence are likely insufficient to explain the findings. The plausibility of cellular memory, possibly systemic memory, is suggested.
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A sample from the paper:
“When they showed me pictures of their son, I knew him directly. I would have picked him out anywhere. He’s systemic information and energy stored within the cells as in me. I know he is in me and he is in love with me. He well (cited in [9], extended in [7,8]). Sylvia was unique be- was always my lover, maybe in another time somewhere. cause she received a substantial amount of new tissue How could he know years before he died that he would (heart and lungs), she was health conscious, and she was die and give his heart to me? How would he know my emotionally open and sensitive. Schwartz and Russek pro- name is Danielle? And then, when they played me some of posed that Claire Sylvia might be the “white crow” of cellu- his music, I could finish the phrases of his songs. I could lar systemic memory [7]. never play before, but after my transplant, I began to love The present paper reports key observations from 10 rep- music. I felt it in my heart. My heart had to play it. I told resentative cases of transplant recipients who were open to my mom I wanted to take guitar lessons, the same instru- sharing experiences of personal changes following their op- ment Paul had played. His song is in me. I feel it a lot at erations that are consistent with the systemic memory pre- night and it’s like Paul is serenading me.
 
Jiří Kroc
added an update
Sivan Gazit, Roei Shlezinger, Galit Perez, Roni Lotan, Asaf Peretz, Amir Ben-Tov, Dani Cohen, Khitam Muhsen, Gabriel Chodick, and Tal Patalon
Abstract
Background Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear.
Methods We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naïve individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel.
Results SARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naïve vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected.
Conclusions This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.
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From the Discussion:
This is the largest real-world observational study comparing natural immunity, gained through previous SARS-CoV-2 infection, to vaccine-induced immunity, afforded by the BNT162b2 mRNA vaccine. Our large cohort, enabled by Israel’s rapid rollout of the mass-vaccination campaign, allowed us to investigate the risk for additional infection – either a breakthrough infection in vaccinated individuals or reinfection in previously infected ones – over a longer period than thus far described. Our analysis demonstrates that SARS-CoV-2-naïve vaccinees had a 13.06-fold increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for a symptomatic disease as well.
Broadening the research question to examine the extent of the phenomenon, we allowed the infection to occur at any time between March 2020 to February 2021 (when different variants were dominant in Israel), compared to vaccination only in January and February 2021. Although the results could suggest waning natural immunity against the Delta variant, those vaccinated are still at a 5.96-fold increased risk for breakthrough infection and at a 7.13-fold increased risk for symptomatic disease compared to those previously infected. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalization compared to those who were previously infected.
Individuals who were previously infected with SARS-CoV-2 seem to gain additional protection from a subsequent single-dose vaccine regimen. Though this finding corresponds to previous reports 24,25, we could not demonstrate significance in our cohort. 
 
Jiří Kroc
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Parisa Ziarati, Bernhard Hochwimmer, Luis Cruz-Rodriguez, Nader Tanideh, Aida Iraji, and Bahareh Kamyab-Moghadas
Journal of Medical Discovery (2021); 6(1) 1-16
DOI:10.24262/jmd.6.1.20070
Abstract
Background Lung cancer is the most frequent cancer and the leading cause of cancer all around the world. Experimental data from Zanjan hospitals revealed a significant urinary arsenic content in lung cancer patients along with some anthropogenic aspects of lifestyle. In this study, the relationship between lung cancer and arsenic as well as other risk factors will be evaluated. Methods In a descriptive-analytic and cross-sectional study performed from 10 January to 30 August 2020, 155 people, 65.2% men and 34.8 % women were selected for evaluation and the amount of arsenic in urine samples were determined with anodic stripping voltammetry method and chemtronics protocol No AN027v2. Results Urinary arsenic concentration in lung cancer patients over 40 years old was 4 times, and in patients, 20-40 years old group was 3 times more than control groups. Urinary arsenic contents in lung cancer patients in all age categories are much lower by drinking Herbal Tea (p <0.001). A strong correlation between gender (male, p <0.001) and depression (p <0.001) with lung cancer was observed. Conclusions The results of the current study reveal that arsenic is one of the main factors contributing to Lung cancer. Besides, statistical analysis showed that men are (3.5 times in a high-risk population), depression, asbestos exposure, working in mine are other significant factors which highly affected patients.
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Herbal tea plant traded in the traditional Zanjan markets comprise of Hibiscus sabdariffa, Camellia sinensis, Mentha piperita and Echium Borage. The common bioactive substances found in Camellia sinensis include flavan-3-ols, proanthocyanidins and flavonols which have anti-inflammatory, and anti-cancer activities [61]. Hibiscus sabdariffa contains organic acids (citric acid and ascorbic acid), phytosterols, polyphenols and anthocyanins. H. sabdariffa shows antioxidant, anti-hypertension, anti-hyperlipidemia, antimicrobial and anti-cancer activity in both human and animal studies [62, 63]. It was suggested that Mentha piperita is rich in flavonoids such as eriocitrin, narirutin, hesperidin, rosmarinic acid with antimicrobial, antiviral, anti-inflammatory, and anti-carcinogenic activity [64, 65]. Several studies confirmed the high potency of Echium Borage for its neuroprotective, anti-inflammatory, and immunomodulatory activities. This therapeutic potency may be due to a high amount of secondary metabolites especially polyphenols and alkaloids [66, 67]. Interestingly, combining different herbs with various bioactive constituents tend to be significantly more effective than the sum of the individual effects of each known compound. Mentioned combined tea may result in preventive of therapeutic synergistic effects intended for oral aqueous consumption. Our evidence stated explicitly that consumption of mentioned local herbal tea used as hot beverages decrease the risk of lung cancer (P value <0.001). A number of studies published support longstanding this claim [61].
 
Jiří Kroc
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Ikuroh Ohsawa, Masahiro Ishikawa, Kumiko Takahashi, Megumi Watanabe, Kiyomi Nishimaki, Kumi Yamagata, Ken-ichiro Katsura, Yasuo Katayama, Sadamitsu Asoh & Shigeo Ohta
Nature Medicine 13 :6 (2007) 688-694
doi:10.1038/nm1577
Abstract:
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H2) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H2 selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H2 did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H2 gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H2 can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.
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From the discussion of the text:
"This study shows that molecular hydrogen can selectively reduce ROS in vitro. As !OH and ONOO– are much more reactive than other ROS (ref. 14), it stands to reason that H2 will react with only the strongest oxidants. This is advantageous for medical procedures, as it means that the use of H2 should not have serious unwanted side effects. It is likely that H2 is mild enough not to disturb metabolic oxidation-reduction reactions or to disrupt ROS involved in cell signaling—unlike some antioxidant supplements with strong reductive reactivity, which increase mortality, possibly by affecting essential defensive mechanisms."
"H2 has a number of advantages as a potential antioxidant: it effectively neutralizes !OH in living cells, and, unlike most known antioxidants, which are unable to successfully target organelles30, it has favorable distribution characteristics: it can penetrate biomembranes and diffuse into the cytosol, mitochondria and nucleus. Despite the moderate reduction activity of H2, its rapid gaseous diffusion might make it highly effective for reducing cytotoxic radicals. Its ability to protect nuclear DNA and mitochondria suggests that it could reduce the risk of life style–related diseases and cancer."
 
Jiří Kroc
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Michael R. Rosen, Ofer Binah, and Shimon Marom
Circulation 108 (2003) 1784-1789
DOI: 10.1161/01.CIR.0000091402.34219.6C
Abstract
Memory is a property of diverse biological systems, including brain and heart. Studies in cortical neuronal networks have identified an increased sensitivity to infrequent (rare) stimulation patterns that can result in their achieving dominance over network firing. This adaptive behavior is applied to the heart in an attempt to explain the ability of pulmonary venous and other ectopic foci to achieve dominance over cardiac rhythm. Developmental changes in determinants of cardiac rhythm are explored as possible determinants of the range of rhythms expressed by the heart. By understanding the mechanisms for these behavior patterns, we may obtain new means for manipulating memory to return dysrhythmic hearts to normal sinus rhythm.
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From the text:
"Once such initially rare patterns emerge and achieve dominance, the challenge is to discover (or rediscover) the signals required to encourage the return of the formerly dominant and normal pattern. Attempts using various atrial pacing paradigms to prevent recurrences of atrial fibrillation may represent one such approach. Another possible approach draws on what we have learned from the developmental biology of the heart. As stated earlier, the stem cells that are the origin of mature cardiac myocytes are not only capable of exhibiting but do in fact exhibit both normal and abnormal mechanisms for impulse initiation and propagation.51–53 The signals that suppress potentially pathological events in favor of those that provide organized activation and propagation within the heart are as yet mysteries to us but are no doubt identifiable. As such, each heart is a repository of the mechanisms for normal and abnormal rhythmic function, and ae need to learn how to recruit the former."
"These thoughts are not meant to denigrate attempts to use pharmacological and other therapies to alter so-called remodeling of myocardium and stress/strain relationships. In the context of the behavior of neural networks, however, such attempts would be considered as acting at the level of modulators of a process rather than at its source. Moreover, answers to the issues raised may also reside in answering such questions as: When is cardiac development complete? What role does aging play in the equation? To what extent does the plasticity seen in neurons characterize the behavior of cardiac myocytes?"
 
Jiří Kroc
added an update
Ali M. Alshami 
Current Pain and Headache Reports 23, 88 (2019)