Low back pain (LBP) is a common disease that imposes a huge social and economic burden on people. Intervertebral disc (IVD) degeneration (IVDD) is often considered to be the leading cause of LBP and further aggravate and cause serious spinal problems. The established treatment strategy for IVDD consists of physiotherapy, pain medication by drug therapy, and, if necessary, surgery, but none of them can be treated from the etiology; that is, it cannot fundamentally reverse IVD and reconstruct the mechanical function of the spine. With the development of nanotechnology and regenerative medicine, nano-drug delivery systems (NDDSs) have improved treatment results because of their good biodegradability, biocompatibility, precise targeted specific drug delivery, prolonged drug release time, and enhanced drug efficacy, and various new NDDSs for drugs, proteins, cells, and genes have brought light and hope for the treatment of IVDD. This review summarizes the research progress of NDDSs in the treatment of IVDD and provides prospects for using NDDSs to address the challenges of IVDD. We hope that the ideas generated in this review will provide insight into the precise treatment of IVDD.
The recent discovery of N-acyl taurines (NATs) as a class of endogenous bioactive lipids and the perspective of their possible pharmacological applications stimulated the development of mass spectrometry-based methods for their quantitative measurements in biological tissues and fluids. We report here for the first time a procedure validated both in liver surrogate matrix and neat solvent (MeOH) based on UPLC-ESI-QqQ analysis for the identification and quantification of NATs in biological tissue extracts. The LC-MS method was based on five representative lipid analogues, including saturated, monounsaturated and polyunsaturated species, namely N-palmitoyl taurine (C16:0 NAT), N-oleoyl taurine (C18:1 NAT), N-arachidonoyl taurine (C20:4 NAT), N-docosanoyl taurine (C22:0 NAT) and N-nervonoyl taurine (C24:1 NAT), and evaluated for specificity, linearity, matrix effect, recovery, repeatability and intermediate precision and accuracy. The method validated in MeOH by internal standard approach (d4-C20:4 NAT) showed excellent linearity in the range 1-300 ng/ml with R always ≥ 0.9996 for all NATs; intra-day and inter-day precision and accuracy were always within the acceptable range. Specificity was assessed on NAT standards in MeOH, applying the confirmation ratio of two diagnostic MRM ion transitions for product ions at m/z 80 and m/z 107 to true samples in the adopted BEH C18 UPLC conditions. Limit of detection (LOD) and limit of quantification (LOQ) were 0.3-0.4 and 1 ng/ml, respectively, for all compounds. The method was successfully applied to assess the levels of NATs in the mouse liver and, for the first time, in varying sections of the intestine (duodenum, jejunum, ileum and colon). NAT levels increased from duodenum to colon, evidencing a remarkable prevalence in the large intestine of C22:0 NAT, typically occurring mainly in the central nervous system. These findings prompt further studies to disclose the biological function of the various members of this class in different peripheral tissues.
By encouraging product repair, companies might increase product durability and minimize waste. However, the effectiveness of such strategies ultimately depends on consumers’ perceptions of the companies’ communications. The current research seeks to determine whether and when product repairability communications can signal product quality. Three quantitative studies and their meta-analysis affirm that repairability communications function as a signal of firms’ CSR orientation and the product’s durability; consumers rate brands that communicate about product repairability more favorably, and this effect grows stronger if they sense that product reliability is decreasing. According to the qualitative study, these effects further depend on factors such as consumers’ attributions of firms’ motives, and the presence of signal endorsers. These results contribute to quality signaling literature by uncovering the role of product repairability communication as a signal of product durability; and highlight the effects of CSR beliefs on consumers’ evaluations in a repair context.
Exercise modulates the circulating levels of the endocannabinoids ligands N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) and possibly the levels of their receptors and downstream signaling in skeletal muscle. The aim of the present study was to investigate the regulation of the endocannabinoid system by several exercise paradigms in human skeletal muscle. A second aim was to compare endocannabinoid regulation in healthy and prediabetic people in response to an acute endurance exercise. Blood and muscle samples were taken before and after resistance and endurance exercise in normoxia and hypoxia to measure plasma endocannabinoid levels as well as muscle protein expression of CB1, CB2 and downstream signaling. We found that: 1) an acute resistance exercise session decreased plasma 2-AG and N-palmitoylethanolamine (PEA) levels in normoxia; 2) 4 weeks resistance training decreased plasma AEA, PEA and N-oleoylethanolamine (OEA) levels in both normoxia and hypoxia; 3) an acute moderate intensity endurance exercise increased plasma OEA levels in the healthy and prediabetic groups in normoxia and hypoxia while plasma 2-AG levels increased in the healthy group and AEA in the prediabetic group only in normoxia. The expression of the cannabinoid receptors was only marginally regulated by acute exercise, hypoxia and prediabetes and downstream signaling did not follow the changes detected in the endocannabinoid ligands. Altogether, our results suggest that resistance and endurance exercise regulate the levels of the endocannabinoid ligands and CB1 expression in opposite ways. The physiological impact of the changes observed in the endocannabinoid ligands in human skeletal muscle after exercise needs further investigation.
As the demand for electrification of means of transportation and storage of electrical energy for later use is skyrocketing, rechargeable Li-ion batteries (LIBs) are at the heart of this revolution. Acknowledging the carbon footprints, environmental concerns and cost of the commercial cathode materials, this is the high time to advocate sustainable alternatives. This review aims at establishing the potential of organic redox-active molecules as a burgeoning class of sustainable solid cathode materials for LIBs. The materials are classified according to their structural features (molecules, metallo-organic complexes, and organic/metal–organic frameworks) and electrochemical performance to lay emphasis on practical applications and bottlenecks in commercialization. However, these materials are still in early stages of development, and new frontiers have been explored in the last five years.
Purpose Metastatic bone disease (MBD) is the most common form of metastases, most frequently deriving from prostate cancer. MBD is screened with bone scintigraphy (BS), which have high sensitivity but low specificity for the diagnosis of MBD, often requiring further investigations. Deep learning (DL) - a machine learning technique designed to mimic human neuronal interactions- has shown promise in the field of medical imaging analysis for different purposes, including segmentation and classification of lesions. In this study, we aim to develop a DL algorithm that can classify areas of increased uptake on bone scintigraphy scans. Methods We collected 2365 BS from three European medical centres. The model was trained and validated on 1203 and 164 BS scans respectively. Furthermore we evaluated its performance on an external testing set composed of 998 BS scans. We further aimed to enhance the explainability of our developed algorithm, using activation maps. We compared the performance of our algorithm to that of 6 nuclear medicine physicians. Results The developed DL based algorithm is able to detect MBD on BSs, with high specificity and sensitivity (0.80 and 0.82 respectively on the external test set), in a shorter time compared to the nuclear medicine physicians (2.5 min for AI and 30 min for nuclear medicine physicians to classify 134 BSs). Further prospective validation is required before the algorithm can be used in the clinic.
Introduction: People with haemophilia (PwH) suffer from knee and ankle joint pain, but the association with structural damage remains underexplored. They report activity limitations but it is unclear which factors contribute to lower limb activity limitations (LL-AL). Aims: This study aimed (i) to analyse the association between ankle joint pain and structure and (ii) explore the contribution of haemophilia-related, individual and psychological factors to LL-AL in PwH. Methods: This study included 104 moderate/severe PwH. Ankle pain intensity was assessed with a numeric rating scale and pain sensitivity with algometry (pressure pain threshold (PPTA )). Ankle structure was assessed with MRI (IPSG-MRI) and ultrasound (HEAD-US), joint health with the Haemophilia Joint Health Score (HJHS). The HAL-LOWCOM subscore evaluated LL-AL. A Spearman correlation analysed the correlation between ankle pain and structure. The contribution of haemophilia-related factors (joint health, overall pain (Brief Pain Inventory-Pain Severity (BPI-PS)), functional status (2-Minute-Walking-Distance, Timed Up and Go); individual factors (age, BMI) and psychological factors (fear and avoidance beliefs over physical activity (FABQ-PA) and work (FABQ-Work), anxiety and depression) to LL-AL was explored using a regression analysis. Results: Only low correlations were found between ankle pain intensity and structure (IPSG-MRI, HEAD-US). PPTA was unrelated to structure. Altogether, HJHS, overall pain (BPI-PS), FABQ-Work and age explained 69% of HAL-LOWCOM variance, with 65% explained by the combination of HJHS and BPI-PS. Conclusion: No meaningful associations were found between ankle pain and structural damage, suggesting that other factors may contribute to PwH's ankle pain. In contrast, mainly haemophilia-related factors explained LL-AL variance.
Parasitoids represent the third trophic level in plant‐insect food webs. They develop in or on herbivorous insects at the second trophic level, which in turn feed on plants that constitute the first trophic level. This food web system might be affected by agricultural landscape and practices. We studied the phenology and population density of Aphis fabae (Hemiptera: Aphididae) and determined the impact of parasitoids in organic fields of beans and beet plants. Twenty leaves per field were collected weekly. For each leaf, the total number of aphids, apterous and alate morphs, the number of mummies, and mortality of aphids were recorded. Our results showed that the phenology of A. fabae varied throughout the season with maximal numbers observed at the beginning of summer. In addition, the production of alate morphs and the proportion of parasitism were positively correlated to an increase in aphid densities. Six parasitoid species were recorded attacking A. fabae in the field, with Lysiphlebus fabarum and Binodoxys angelicae (Hymenoptera: Aphidiinae) being the most abundant parasitoids. Field characteristics and availability of host plants in the surroundings affected A. fabae density. Lysiphlebus fabarum and B. angelicae appeared to be good biocontrol candidates against A. fabae. Dans le système de chaine alimentaire d'agriculture, les parasitoïdes représentent le troisième niveau trophique qui pondent dans les pucerons (deuxième niveau trophique) nourrissant sur des cultures agricoles. Cette chaîne pourrait être influencer par les conditions de terrain et l'application agriculture. Dans cet étude, on s'est focalisé sur la phénologie et la densité d'Aphis fabae (Hemiptera: Aphididae) et a déterminé l'impact de parasitoïdes présents dans les champs organiques de féveroles et de betteraves. Chaque semaine, 20 feuilles issues d'une vingtaine de plantes infestées (par site), ont été collectées pendant la saison. Pour chaque feuille, le nombre de pucerons et leurs stades, ainsi que le nombre de momies présentes ont été enregistrés. Nos résultats ont montré que la phénologie d'A. fabae a varié selon la saison. Le nombre de pucerons était plus élevé en printemps et au début de l'été. En outre, la production des individus ailés et le parasitisme étaient positivement liés à l'augmentation de la densité de pucerons. Six espèces de parasitoïdes ont été enregistrées, avec Lysiphlebus fabarum et Binodoxys angelicae (Hymenoptera: Aphidiinae) étant les plus abondantes. Les caractéristiques du terrain y compris le site et la disponibilité des plantes hôtes dans les alentours des cultures agricoles pourraient influencer la densité de pucerons. L'abondance des L. fabarum et B. angelicae fait de ces deux espèces des excellents candidats pour le développement d'un programme de lutte biologique contre A. fabae. The production of alate morphs and the proportion of parasitism were positively correlated to the aphid densities. Lysiphlebus fabarum and Binodoxys angelicae appeared to be good candidates against Aphis fabae. The field characteristics and the availability of host plants in the surroundings affected Aphis fabae density. The production of alate morphs and the proportion of parasitism were positively correlated to the aphid densities. Lysiphlebus fabarum and Binodoxys angelicae appeared to be good candidates against Aphis fabae. The field characteristics and the availability of host plants in the surroundings affected Aphis fabae density.
This study answers two research questions: (1) How do 12- and 13-year-old students respond to metacognitive questions posed during a complex task in mathematics or in science and (2) Do these responses differ by discipline? Content analysis was applied to responses collected from 92 students from a French-speaking Belgian school. The results showed that students are able to respond to metacognitive questions. However, the responses were not clear and were simplistic when they talked about their strategies. The difficulties students faced in developing their responses were identical in both disciplines.
Metal dodecaborates (MxB12H12) are a versatile class of materials used in polymer chemistry and cancer treatment and are promising candidates as electrolytes for solid-state batteries. However, a general and scalable approach has not yet been developed for producing high-purity B12H122- derivatives. In this work, we report a simple, efficient, and environmentally benign solvothermal method to prepare diffraction and 11B NMR pure Na2B12H12 (85% yield) and K2B12H12 (84% yield). This new synthetic approach is based on the use of the borane dimethyl sulfide complex (DMS·BH3) and borohydrides (NaBH4, KBH4) heated at different temperatures in diglyme in an autoclave. It was found that high-purity Na2B12H12·diglyme solvate is obtained via an intermediate formation of B3H8-, B9H14-, and B11H14-, which are all soluble in diglyme. Heating under vacuum is shown to be efficient for removing the coordinated diglyme, allowing the formation of unsolvated Na2B12H12. Autoclave synthesis starting from KBH4 directly yields solvent-free K2B12H12, and ball-milling KBH4 prior to the synthesis enabling us to significantly improve the final yield. The new synthetic method paves the way for large-scale synthesis of MxB12H12 derivatives, enabling to envisage a wider scope of practical applications.
Introduction: According to the recent updates from World Health Organization, liver diseases are the 12th most common cause of mortality globally. Currently, orthotopic liver transplantation (OLT) is the most effective and the only treatment strategy for end-stage liver diseases. Owing to several shortcomings like finite numbers of healthy organ donors, lifelong immunosuppression, and complexity of the procedure, cell and cell-derivities therapies have emerged as a potential therapeutic alternative for a broad range of liver diseases. Various cell types and therapies have been proposed and their therapeutic effects evaluated in preclinical or clinical studies, including hepatocytes, hepatocyte-like cells (HLCs) derived from stem cells, human liver stem cells (HLSCs), combination therapies with various types of cells, organoids, and implanable cell-biomaterial constructs with synthetic and natural polymers or even decellularized extracellular matrix (ECM). Areas covered: In this review we highlighted the current status of cell and cell-derivitie-based therapies for liver diseases. Furthermore, we discussed future prospects of using HLCs, liver organoids, and their combination therapies. Expert opinion: Promising application of stem cell-based techniques including iPSC technology has been integrated into novel technics such as gene editing, directed differentiation and organoid technology. iPSCs offer promising prospects to represent novel therapeutic strategies and modeling diseases for liver disorders.
Energy crops on marginal lands are seen as an interesting option to increase biomass contribution to the primary energy mix. However, in the literature there is currently a lack of integrated assessments of margin land availability, energy crop production potential and supply chain optimisation. Assessing the potential and the cost of these resources in a given region is therefore a difficult task. This work also emphasises the importance on a clear definition and discussion about marginal lands and the related ethical issues embedded in the concept to ensure positive societal impacts of the results. This study proposes a methodology to estimate and analyse, in terms of economic costs, the potential of miscanthus grown on marginal lands from the production to the final point of use. Different datasets are assembled and a supply chain optimisation model is developed to minimize the total cost of the system. Miscanthus is used as a representative energy crop for the Belgian and French case studies. High temperature heat demand is considered as final use. The miscanthus can be traded by truck either in the form of chips or pellets. The results show that the miscanthus on marginal lands could supply high temperature heat up to 38 TWh in France and 1,4 TWh in Belgium with an average cost of around 50 €/t. The different sensitivity analyses showed that the yield variation has the strongest influence on the final cost, together with the distances and the cost of production of miscanthus. The main pattern observed is the local consumption of miscanthus chips and export of the surplus (if any) to the neighbouring regions. Pellets are only of marginal interest for France and are never observed for Belgium. Distances and availability of sufficient feedstocks are the two main parameters impacting the production of pellets.
This article summarises the activities of the Bacterial Viruses Subcommittee of the International Committee on Taxonomy of Viruses for the period of March 2021−March 2022. We provide an overview of the new taxa proposed in 2021, approved by the Executive Committee, and ratified by vote in 2022. Significant changes to the taxonomy of bacterial viruses were introduced: the paraphyletic morphological families Podoviridae, Siphoviridae, and Myoviridae as well as the order Caudovirales were abolished, and a binomial system of nomenclature for species was established. In addition, one order, 22 families, 30 subfamilies, 321 genera, and 862 species were newly created, promoted, or moved.
Muscle glucose transport activity increases with an acute bout of exercise, a process that is accomplished by the translocation of glucose transporters to the plasma membrane. This process remains intact in the skeletal muscle of individuals with insulin resistance and type 2 diabetes mellitus (T2DM). Exercise training is, therefore, an important cornerstone in the management of individuals with T2DM. However, the acute systemic glucose responses to carbohydrate ingestion are often augmented during the early recovery period from exercise, despite increased glucose uptake into skeletal muscle. Accordingly, the first aim of this review is to summarize the knowledge associated with insulin action and glucose uptake in skeletal muscle and apply these to explain the disparate responses between systemic and localized glucose responses post-exercise. Herein, the importance of muscle glycogen depletion and the key glucoregulatory hormones will be discussed. Glucose uptake can also be stimulated independently by hypoxia; therefore, hypoxic training presents as an emerging method for enhancing the effects of exercise on glucose regulation. Thus, the second aim of this review is to discuss the potential for systemic hypoxia to enhance the effects of exercise on glucose regulation.
Detecting cancer at the early stage of the disease is crucial to keep the best chance for successful treatment. The recent development of genomic screening, a methodology that is addressed to asymptomatic patients presumably at risk of carcinogenesis, has stimulated the quest for new tools able to signal the level of risk. Carcinogenesis has been associated to chronic oxidative stress exceeding the antioxidant defenses and leading to critical genome alteration levels. The telomeric regions are presumably the most exposed to oxidative stress due to their high concentration of guanine (i.e., the easiest oxidizable nucleic base). Accumulation of 8-oxoguanine in telomeres, thus oxidative lesions, was reportedly associated with telomeric crisis and carcinogenesis. In this study, we report on the capacity of Ru(II) polyazaaromatic complexes to photoprobe 8-oxoguanine into the human telomeric sequence with the view of developing new tools for cancer risk screening.
Quite strikingly, there is significant variation in Covid-19 vaccine coverage around the world. Some countries do not progress from around 2-3% while others are close to 100% coverage. In addition to some already known economic, health and sociodemographic predictors, the present research is interested in emotional factors that may predict a significant part of this crosscountry variation. We examined the personality factor Neuroticism, which corresponds to the relatively stable tendency to experience negative emotions, anxiety and low tolerance for stress. Results confirm that gross domestic product represents around 50 percent of crosscountry variation. Neuroticism added 6 to 9 percent of inter-country variation in vaccination coverage. The results are discussed in relation to the associations between Neuroticism, increased worry, greater attention to Covid-19 related information and confidence, as well as lower vaccine hesitancy. Public Access: https://rdcu.be/c3S6M
International Disaster Law (IDL) does not provide a uniform legal framework contained in a single instrument. Instead, it comprises various treaties, customary international law, general principles of law, and soft law instruments. In order to forge a uniform instrument for regulating disaster relief and disaster risk reduction, the International Law Commission (ILC), upon the recommendation of the UN General Assembly, incorporated “Protection of persons in the event of disasters” into its program of work in 2007. ILC appointed Eduardo Valencia-Ospina (Colombia) as the Special Rapporteur for the topic. Finally, ILC adopted the Draft Articles on the Protection of Persons in the Event of Disasters (DAPPED) in 2016 and recommended the UN General Assembly consider the possibility of developing a Convention based on it in the same year. Now, DAPPED is under the consideration of the Sixth Committee of UNGA. DAPPED added a novel discourse to IDL. The present chapter will, following introductory words, highlight the drafting history of DAPPED. Then, it will provide an overview of the contents of DAPPED and its normative framework, respectively. The final section of this chapter will deal with the possibility of convening a Convention based on DAPPED and its prospects as other sources of international law.
Purpose To guarantee the safety of the public, clinicians and patients during the COVID-19 pandemic, hospital visits were severely restricted internationally. There are limited data on the precise impact of these visiting restrictions on Intensive Care Unit clinicians. Our objectives therefore were to explore the impact of family visitation restrictions on clinicians and care delivery and describe innovation alongside areas for potential improvement. Methods A qualitative approach using focus groups was employed. We recruited members of the multi-disciplinary team from Spain, France and the UK. Framework analysis was used to synthesize and interpret data. Results In total, 28 staff from multiple international sites contributed to data across six focus groups: 12 from the UK, 9 from France and 7 from Spain. In relation to the key aims, we derived four themes: the emergence of new technologies, relationships and rapport establishment, communication challenges and end-of-life care provision. Across each theme, the overarching concepts of clinician emotional exhaustion and emotional distress emerged alongside the negative impact on job satisfaction. Conclusion The impact of COVID-19 family visitation restrictions is far reaching. Future research should examine the wider impact of family presence in the ICU.
Arbuscular mycorrhizal (AM) fungi play key roles in soil fertility of agroecosystems. They develop dense extraradical mycelial (ERM) networks via mechanisms such as hyphal anastomosis. These connections between hyphae can be affected by agricultural practices such as the use of fungicides, but how these compounds affect anastomosis formation within and more importantly between networks of the same AM fungal strain remains poorly unexplored. Here, the impact of azoxystrobin, pencycuron, flutolanil, and fenpropimorph at 0.02 and 2 mg L ⁻¹ were tested in vitro on the anastomosis formation within and between networks of Rhizophagus irregularis MUCL 41833. Azoxystrobin and fenpropimorph had a particularly detrimental impact, at the highest concentration (2 mg L ⁻¹ ), on the number of anastomoses within and between networks, and for fenpropimorph in particular at both concentrations (0.02 and 2 mg L ⁻¹ ) on the number of anastomoses per length of hyphae. Curiously fenpropimorph at 0.02 mg L ⁻¹ significantly stimulated spore production, while with azoxystrobin, the reverse was observed at 2 mg L ⁻¹ . The two other fungicides, pencycuron and flutolanil, had no detrimental effects on spore production or anastomosis formation within and between networks. These results suggest that fungicides with different modes of action and concentrations differentially affect anastomosis possibly by altering the hyphal tips of AM fungi and may thus affect the capacity of AM fungi to develop large hyphal networks exploring and exploiting the soil at the service of plants.
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