We report a new sensitive label-free electrochemical immunosensor to detect Vitamin D3 (25-OHD3) in untreated serum samples. To this aim, a graphite screen printed electrode (SPE) was modified using cysteamine (CYM) functionalized core-shell magnetic nanoparticles ([email protected]) then, the 25-OHD3 antibody (AbD) was immobilized via glutaraldehyde crosslinking. The several steps involved in the immunosensor development and 25-OHD3 analysis were monitored by using differential pulse voltammetry (DPV). The developed immunosensor showed a LOD of 2.4 ng mL⁻¹ and a linear range between 7.4 and 70 ng mL⁻¹. The effectiveness of the immunosensor in human serum analysis was assessed by comparing the results obtained with the chemiluminescence-immunoassay (CLIA) reference method. The high sensitivity and excellent agreement with the reference method suggest its potential use as a POCT to monitor hypovitaminosis 25-OHD levels.
As regioisomers/bioisosteres of 1a, a 4-phenylbenzamide tranylcypromine (TCP) derivative previously disclosed by us, we report here the synthesis and biological evaluation of some (hetero)arylbenzoylamino TCP derivatives 1b-6, in which the 4-phenyl moiety of 1a was shifted at the benzamide C3 position or replaced by 2- or 3-furyl, 2- or 3-thienyl, or 4-pyridyl group, all at the benzamide C4 or C3 position. In anti-LSD1-CoREST assay, all the meta derivatives were more effective than the para analogues, with the meta thienyl analogs 4b and 5b being the most potent (IC50 values ¼ 0.015 and 0.005 lM) and the most selective over MAO-B (selectivity indexes: 24.4 and 164). When tested in U937 AML and prostate cancerLNCaP cells, selected compounds 1a,b, 2b, 3b, 4b, and 5a,b displayed cell growth arrest mainly in LNCaPcells. Western blot analyses showed increased levels of H3K4me2 and/or H3K9me2 confirming the involvement of LSD1 inhibition in these assays.
Circular RNAs (circRNAs) are expressed and are regulated in many biological processes but little is known about their ability to directly control mRNA homeostasis. We show that circRNA zinc finger protein 609 (circZNF609) interacts with several mRNAs increasing the final protein levels, which in the case of the cytoskeleton-associated protein 5 (CKAP5) leads to a stabilized microtubule cytoskeleton and an enhanced tumor cell proliferation.
Background The role of allergic sensitization seems to be protective against SARS CoV2 infection. The aim of this study was to evaluate, using online surveys, the impact of COVID-19 on Italian allergic children, comparing the prevalence of AR and asthma symptoms between the first and second pandemic wave. Methods Both surveys were emailed to Italian pediatricians in April 2020 (first survey) and in March 2021 (second survey). The first one was related to the impact of COVID-19 and the most frequently reported symptoms. The second one was superimposed on the previous one, taking into account some additional aspects in the management of disease. Results A total of 99 pediatricians participated in the first survey and 267 in the second one. The first survey showed that, asthma and allergic rhinoconjunctivitis prevalence was mostly between 0 and 20% throughout the country. The second survey showed a lower prevalence of both diseases nationwide in comparison to the first one. Comparing the two surveys, statistically significant differences were reported only in the distribution of asthma prevalence in Southern Italy while no differences were highlighted in the North and in the Center. Finally regarding allergic rhinoconjunctivitis prevalence, no differences were noticed nationwide. Conclusions Allergic rhinoconjunctivitis and asthma, if under control, did not represent risk factors for the susceptibility to SARS CoV2. Therefore, it is strongly recommended to continue therapies during COVID-19 outbreak, according to the international guidelines. However, being COVID-19 a new disease, actual knowledge will undergo continuous improvements over time.
Motivated by the recent claim of hot superconductivity with critical temperatures up to 550 K in La + x hydrides, we investigate the high-pressure phase diagram of compounds that may have formed in the experiment, using first-principles calculations for evolutionary crystal structure prediction and superconductivity. Starting from the hypothesis that the observed T c may be realized by successive heating upon a pre-formed LaH 10 phase, we examine plausible ternaries of lanthanum, hydrogen and other elements present in the diamond anvil cell: boron, nitrogen, carbon, platinum, gallium, gold. We find that only boron and, to a lesser extent, gallium form metastable superhydride-like structures that can host high- T c superconductivity, but the predicted T c ’s are incompatible with the experimental reports. Our results indicate that, while the claims of hot superconductivity should be reconsidered, it is very likely that unknown H-rich ternary or multinary phases containing lanthanum, hydrogen, and possibly boron or gallium may have formed under the reported experimental conditions, and that these may exhibit superconducting properties comparable, or even superior, to those of currently known hydrides.
The fast diffusion of the SARS-CoV-2 pandemic have called for an equally rapid evolution of the therapeutic options. The Human recombinant monoclonal antibodies (mAbs) have recently been approved by the Food and Drug Administration (FDA) and by the Italian Medicines Agency (AIFA) in subjects aged ≥12 with SARS-CoV-2 infection and specific risk factors. Currently the indications are specific for the use of two different mAbs combination: Bamlanivimab+Etesevimab (produced by Eli Lilly) and Casirivimab+Imdevimab (produced by Regeneron). These drugs have shown favorable effects in adult patients in the initial phase of infection, whereas to date few data are available on their use in children. AIFA criteria derived from the existing literature which reports an increased risk of severe COVID-19 in children with comorbidities. However, the studies analyzing the determinants for progression to severe disease are mainly monocentric, with limited numbers and reporting mostly generic risk categories. Thus, the Italian Society of Pediatrics invited its affiliated Scientific Societies to produce a Consensus document based on the revision of the criteria proposed by AIFA in light of the most recent literature and experts’ agreement. This Consensus tries to detail which patients actually have the risk to develop severe disease, analyzing the most common comorbidities in children, in order to detail the indications for mAbs administration and to guide the clinicians in identifying eligible patients.
The accurate simulation of additional interactions at the ATLAS experiment for the analysis of proton–proton collisions delivered by the Large Hadron Collider presents a significant challenge to the computing resources. During the LHC Run 2 (2015–2018), there were up to 70 inelastic interactions per bunch crossing, which need to be accounted for in Monte Carlo (MC) production. In this document, a new method to account for these additional interactions in the simulation chain is described. Instead of sampling the inelastic interactions and adding their energy deposits to a hard-scatter interaction one-by-one, the inelastic interactions are presampled, independent of the hard scatter, and stored as combined events. Consequently, for each hard-scatter interaction, only one such presampled event needs to be added as part of the simulation chain. For the Run 2 simulation chain, with an average of 35 interactions per bunch crossing, this new method provides a substantial reduction in MC production CPU needs of around 20%, while reproducing the properties of the reconstructed quantities relevant for physics analyses with good accuracy.
Background The current global pandemic of Coronavirus Disease 2019 (COVID-19) has profoundly impacted medical practitioners worldwide. This survey was formed by the Radiology Section of the European Union of Medical Specialists (UEMS) to establish the use of personal protective equipment (PPE) by European radiologists committed to providing face-to-face ultrasound services after the first few months of the COVID-19 global pandemic. Results The results showed a heterogeneous picture within Europe regarding PPE used by European radiologists providing face-to-face ultrasound services. Ranging from full protection including full limb protection and double gloves to no PPE at all. In general, European radiologists were using more PPE when providing face-to-face ultrasound services in COVID-19 positive patients than in COVID-19 asymptomatic patients. In many member countries of the Radiology Section of the UEMS (19/30), there were no national guidelines with regard to the use of PPE by healthcare professionals committed to providing face-to-face ultrasound services. Conclusions Our results showed that harmonization on a European level regarding the recommended use of PPE for European radiologists providing face-to-face ultrasound services is lacking. When the position statements and best practice recommendations on standards in ultrasound are revised, we recommend adding a paragraph on PPE.
Background Migraine has complex pathophysiological characteristics and episodic attacks. To decipher the cyclic neurophysiological features of migraine attacks, in this study, we compared neuronal excitability in the brainstem and primary somatosensory (S1) region between migraine phases for 30 consecutive days in two patients with episodic migraine. Methods Both patients underwent EEG recording of event-related potentials with the somatosensory and paired-pulse paradigms for 30 consecutive days. The migraine cycle was divided into the following phases: 24–48 h before headache onset ( Pre2 ), within 24 h before headache onset ( Pre1 ), during the migraine attack ( Ictal ), within 24 h after headache offset ( Post1 ), and the interval of ˃48 h between the last and next headache phase ( Interictal ). The normalised current intensity in the brainstem and S1 and gating ratio in the S1 were recorded and examined. Results Six migraine cycles (three for each patient) were analysed. In both patients, the somatosensory excitability in the brainstem (peaking at 12–14 ms after stimulation) and S1 (peaking at 18–19 ms after stimulation) peaked in the Pre1 phase. The S1 inhibitory capability was higher in the Ictal phase than in the Pre1 phase. Conclusion This study demonstrates that migraine is a cyclic excitatory disorder and that the neural substrates involved include the somatosensory system, starting in the brainstem and spanning subsequently to the S1 before the migraine occurs. Further investigations with larger sample sizes are warranted.
Objective: Anatomical parameters and pathologies that can affect the critical shoulder angle (CSA) are subjects of discussion. To date, we do not know if the CSA value changes in the different decades of life in a population characterized by the same ethnicity, nor if there are differences related to gender or side. This study hypothesizes that age and gender may affect the CSA. Methods: Patients older than 15 years old affected by a shoulder trauma and who were discharged with a diagnosis of shoulder contusion were enrolled. A true AP view of the shoulder was obtained as well as data regarding age and gender of all participants. The CSA was measured by three authors, and interoperator reliability was assessed. Eight subcategories, according to decades of life, were considered. Finally, the studied population was divided into three subcategories according to CSA values (< 30°; 30-35°; ≥ 35°). Results: The initial sample comprised 3587 shoulder X-rays. The interobserver reproducibility was high, with an intraclass correlation coefficient of 0.865 (95% CI 0.793-0.915). Two thousand eight hundred seventy-three radiograms were excluded. The studied group comprised 714 patients [431 females, 283 males; mean age (SD): 47.2 (20.9) years, range: 11-93 years]. The mean CSA was 33.6° (range: 24-50°; SD: 3.9°). The mean CSA values in females and males were 33.7°and 33.5°, respectively. The mean CSA values of the right and left shoulders were 33.3° and 33.9°, respectively (p > 0.05). Linear regression analysis showed a CSA increase by 0.04° every year. The mean CSA in subjects aged between 15 and 19 years was significantly lower than all the other groups, except for patients older than 80 years. No significant differences were found between CSA subcategories, gender, or side. Conclusions: In the general population, the mean CSA value was 33.6°. No significant differences were found regarding the mean CSA value according to gender or side. A significant positive linear correlation between CSA and age was detected. In each decade of life, the CSA value, which is genetically determined, shows a large variability. Level of evidence: IV.
Background The timing of a return to sport (RTS) after anterior cruciate ligament reconstruction (ACLR) represents a major subject of debate in sports medicine practice. Recently, the Knee Santy Athletic Return to Sport (K-STARTS) composite test was validated. This consists of a battery of physical tests and a psychological evaluation using the anterior cruciate ligament–return to sport after injury scale (ACL-RSI). This study aimed to translate the ACL-RSI and K-STARTS from English to Italian and determine the scale’s reliability and validity in an Italian context. Methods The translation and cultural adaptation process was performed according to the guidelines for the cross-cultural adaptation of self-report measures. The patients were asked to fill an anonymized online form created for this purpose that included the KOOS, the Lysholm, the IKDC-SKF, and the Italian translation of the ACL-RSI (ACL-RSI-It). After 1 week, the attendees were asked to repeat the ACL-RSI-It to investigate the test–retest reliability. Results The final study population comprised 115 patients who underwent ACLR, with a mean follow-up of 37.37 ± 26.56 months. The ACL-RSI-It showed axcellent internal consistency (Cronbach’s α = 0.963), reliability (test–retest ICC = 0.966), and good construct validity (positive correlations with the other scales were above 75%). Conclusions The ACL-RSI-It is valid, reliable, and comparable to the original English version of the questionnaire for Italian-speaking patients. It can be used to assess the psychological readiness of patients for a RTS after primary and unilateral ACLR, and can be integrated into the Italian K-STARTS test. Level of evidence Level II.
Background Since the appearance of the first report on postoperative cognitive impairment in 1955, the number of papers focusing on perioperative neurocognitive disorders (PND) has constantly increased, both in the field of basic science and clinical research. A critical comprehensive review may explore the perception of how noteworthy PND is for physicians and clinical researchers. The aim of this systematic review is to describe how the clinical papers published to date with PND as primary or secondary outcome have changed over time in terms of editorial characteristics. Results A literature search was performed on PubMed, Embase, CINAHL, Cochrane, Scopus, and Web of Science databases, up to March 2021. Human prospective or retrospective clinical studies in which incidence, risk factors, treatments, or outcomes associated with PND are described among primary or secondary outcomes were included. A total of 2109 articles were considered. Conclusions The bibliometric analysis suggests a stable increase in attention towards PND, particularly in general surgery adult-elderly patients, and underlines the importance for the clinicians not to underestimate this specific field.
One of the most fascinating areas in the field of smart biopolymers is biomolecule sensing. Accordingly, multifunctional biomimetic, biocompatible, and stimuli-responsive materials based on hydrogels have attracted much interest. Within this framework, the design of nanostructured materials that do not require any external energy source is beneficial for developing a platform for sensing glucose in body fluids. In this article, we report the realization and application of an innovative platform consisting of two outer layers of a nanocomposite plasmonic hydrogel plus one inner layer of electrospun mat fabricated by electrospinning, where the outer layers exploit photoinitiated free radical polymerization, obtaining a compact and stable device. Inspired by the exceptional features of chameleon skin, plasmonic silver nanocubes are embedded into a poly(N-isopropylacrylamide)-based hydrogel network to obtain enhanced thermoresponsive and antibacterial properties. The introduction of an electrospun mat creates a compatible environment for the homogeneous hydrogel coating while imparting excellent mechanical and structural properties to the final system. Chemical, morphological, and optical characterizations were performed to investigate the structure of the layers and the multifunctional platform. The synergetic effect of the nanostructured system’s photothermal responsivity and antibacterial properties was evaluated. The sensing features associated with the optical properties of silver nanocubes revealed that the proposed multifunctional system is a promising candidate for glucose-sensing applications.
Background Circulating tumor cells (CTCs) are responsible for the metastatic dissemination of colorectal cancer (CRC) to the liver, lungs and lymph nodes. CTCs rarity and heterogeneity strongly limit the elucidation of their biological features, as well as preclinical drug sensitivity studies aimed at metastasis prevention. Methods We generated organoids from CTCs isolated from an orthotopic CRC xenograft model. CTCs-derived organoids (CTCDOs) were characterized through proteome profiling, immunohistochemistry, immunofluorescence, flow cytometry, tumor-forming capacity and drug screening assays. The expression of intra- and extracellular markers found in CTCDOs was validated on CTCs isolated from the peripheral blood of CRC patients. Results CTCDOs exhibited a hybrid epithelial-mesenchymal transition (EMT) state and an increased expression of stemness-associated markers including the two homeobox transcription factors Goosecoid and Pancreatic Duodenal Homeobox Gene-1 (PDX1), which were also detected in CTCs from CRC patients. Functionally, CTCDOs showed a higher migratory/invasive ability and a different response to pathway-targeted drugs as compared to xenograft-derived organoids (XDOs). Specifically, CTCDOs were more sensitive than XDOs to drugs affecting the Survivin pathway, which decreased the levels of Survivin and X-Linked Inhibitor of Apoptosis Protein (XIAP) inducing CTCDOs death. Conclusions These results indicate that CTCDOs recapitulate several features of colorectal CTCs and may be used to investigate the features of metastatic CRC cells, to identify new prognostic biomarkers and to devise new potential strategies for metastasis prevention.
Background Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed. Main findings Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12 weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4 weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3 months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type. Conclusions Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue.
Background Measurement of cardiac structure and function from images (e.g. volumes, mass and derived parameters such as left ventricular (LV) ejection fraction [LVEF]) guides care for millions. This is best assessed using cardiovascular magnetic resonance (CMR), but image analysis is currently performed by individual clinicians, which introduces error. We sought to develop a machine learning algorithm for volumetric analysis of CMR images with demonstrably better precision than human analysis. Methods A fully automated machine learning algorithm was trained on 1923 scans (10 scanner models, 13 institutions, 9 clinical conditions, 60,000 contours) and used to segment the LV blood volume and myocardium. Performance was quantified by measuring precision on an independent multi-site validation dataset with multiple pathologies with n = 109 patients, scanned twice. This dataset was augmented with a further 1277 patients scanned as part of routine clinical care to allow qualitative assessment of generalization ability by identifying mis-segmentations. Machine learning algorithm (‘machine’) performance was compared to three clinicians (‘human’) and a commercial tool (cvi42, Circle Cardiovascular Imaging). Findings Machine analysis was quicker (20 s per patient) than human (13 min). Overall machine mis-segmentation rate was 1 in 479 images for the combined dataset, occurring mostly in rare pathologies not encountered in training. Without correcting these mis-segmentations, machine analysis had superior precision to three clinicians (e.g. scan-rescan coefficients of variation of human vs machine: LVEF 6.0% vs 4.2%, LV mass 4.8% vs. 3.6%; both P < 0.05), translating to a 46% reduction in required trial sample size using an LVEF endpoint. Conclusion We present a fully automated algorithm for measuring LV structure and global systolic function that betters human performance for speed and precision.
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