An Evidence-Based Approach to Utilizing Cold Therapies for Post-Exercise Recovery

Whilst cold therapies such as cold-water immersion are regularly used in practice, the practical application does not always align with best practices. In this commentary, we highlight the key components of the British Association of Sport and Exercise Sciences (BASES) Expert Statement on the use of cooling therapies for post-exercise recovery and provide additional discussion on the empirical evidence and rationale that informed our perspective. We developed a series of specific questions to ensure that cold therapy recovery protocols are context-specific and tailored to the needs of the individual athletes. These questions, which cover the WHEN, WHAT, and HOW of cold therapy, were central to the development of the Expert Statement. This was presented as a decision tree to ensure that key messages could be concisely disseminated across a range of sporting environments and populations (e.g., gyms, locker rooms, and treatment rooms), supporting and informing decision-making for those wanting to use cold therapy to assist their recovery in line with previously published peer-reviewed work. Discussion points included the suitability of cooling therapies in some contexts, how athletes’ choice of cooling mode should be largely driven by practicalities (e.g., budget and availability), and, lastly, future research directions

Effect of vitamin D supplementation on blood pressure:a systematic review and meta-analysis incorporating individual patient data

D-PRESSURE Collaboration: et al.[Importance]: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.[Objective]: To systematically review whether supplementation with vitamin D or its analogues reduce BP.[Data Sources]: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014.[Study Selection]: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms.[Data Extraction and Synthesis]: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model.[Main Outcomes and Measures]: Difference in SBP and DBP measured in an office setting.[Results]: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, −0.8 to 0.8] mm Hg; P = .97; I2 = 21%) or DBP (effect size, −0.1 [95% CI, −0.6 to 0.5] mm Hg; P = .84; I2 = 20%). Similar results were found analyzing individual patient data for SBP (effect size, −0.5 [95% CI, −1.3 to 0.4] mm Hg; P = .27; I2 = 0%) and DBP (effect size, 0.2 [95% CI, −0.3 to 0.7] mm Hg; P = .38; I2 = 0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy.[Conclusions and Relevance]: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.Peer reviewe

Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis.

Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively).IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease

A 50 pc Scale View of Star Formation Efficiency across NGC 628

Star formation is a multi-scale process that requires tracing cloud formation and stellar feedback within the local (≲kpc) and global galaxy environment. We present first results from two large observing programs on the Atacama Large Millimeter/submillimeter Array (ALMA)and the Very Large Telescope/Multi Unit Spectroscopic Explorer(VLT/MUSE), mapping cloud scales (1″ = 47 pc) in both molecular gas and star-forming tracers across 90 kpc2 of the central disk of NGC 628 to probe the physics of star formation. Systematic spatial offsets between molecular clouds and H ii regions illustrate the time evolution of star-forming regions. Using uniform sampling of both maps on 50-500 pc scales, we infer molecular gas depletion times of 1-3 Gyr, but also find that the increase of scatter in the star formation relation on small scales is consistent with gas and H ii regions being only weakly correlated at the cloud (50 pc) scale. This implies a short overlap phase for molecular clouds and H ii regions, which we test by directly matching our catalog of 1502 H ii regions and 738 GMCs. We uncover only 74 objects in the overlap phase, and we find depletion times >1 Gyr, significantly longer than previously reported for individual star-forming clouds in the Milky Way. Finally, we find no clear trends that relate variations in the depletion time observed on 500 pc scales to physical drivers (metallicity, molecular and stellar-mass surface density, molecular gas boundedness) on 50 pc scales.We thank the referee for helpful comments that improved this work. K.K. gratefully acknowledges support from grant KR 4598/1-2 from the German Research Foundation (DFG) Priority Program 1573. J.M.D.K. and M.C. gratefully acknowledge funding from the DFG in the form of an Emmy Noether Research Group (grant No. KR4801/1-1). J.M.D.K. gratefully acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme via the ERC Starting Grant MUSTANG (grant agreement No. 714907). B.G. gratefully acknowledges the support of the Australian Research Council as the recipient of a Future Fellowship (FT140101202). F.B. acknowledges funding from the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement No. 726384—EMPIRE). G.B. is supported by CONICYT/ FONDECYT, Programa de Iniciación, Folio 11150220. A.H. acknowledges support from the Centre National d’Etudes Spatiales (CNES). E.R. acknowledges the support of the Natural Sciences and Engineering Research Council of Canada (NSERC), funding reference No. RGPIN-2017-03987. R.M. and E.S. acknowledge funding from the ERC under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement No. 694343). J.P. acknowledges support by the Programme National “Physique et Chimie du Milieu Interstellaire”(PCMI) of CNRS/INSU with INC/INP co-funded by CEA and CNES

Zebrafish Models in NeuroPsychopharmacology and CNS Drug Discovery

Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets

Moiré band model and band gaps of graphene on hexagonal boron nitride

Nearly aligned graphene on hexagonal boron nitride (G/BN) can be accurately modeled by a Dirac Hamiltonian perturbed by smoothly varying moir\'e pattern pseudospin fields. Here, we present the moir\'e-band model of G/BN for arbitrary small twist angles under a framework that combines symmetry considerations with input from ab-initio calculations. Our analysis of the band gaps at the primary and secondary Dirac points highlights the role of inversion symmetry breaking contributions of the moir\'e patterns, leading to primary Dirac point gaps when the moir\'e strains give rise to a finite average mass, and to secondary gaps when the moir\'e pseudospin components are mixed appropriately. The pseudomagnetic strain fields which can reach values of up to $\sim$40 Tesla near symmetry points in the moir\'e cell stem almost entirely from virtual hopping and dominate over the contributions arising from bond length distortions due to the moir\'e strains.Comment: 14 pages, 8 figures, 3 table

A vaccine displaying a trimeric influenza-A HA stem protein on capsid-like particles elicits potent and long-lasting protection in mice

Due to constant antigenic drift and shift, current influenza-A vaccines need to be redesigned and administered annually. A universal flu vaccine (UFV) that provides long-lasting protection against both seasonal and emerging pandemic influenza strains is thus urgently needed. The hemagglutinin (HA) stem antigen is a promising target for such a vaccine as it contains neutralizing epitopes, known to induce cross-protective IgG responses against a wide variety of influenza subtypes. In this study, we describe the development of a UFV candidate consisting of a HAstem trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HAstem trimer, the CLP-HAstem particles induced a more potent, long-lasting immune response and were able to protect mice against both homologous and heterologous H1N1 influenza challenge, even after a single dose

Cholinergic modulation of disorder-relevant human defensive behaviour in generalised anxiety disorder

Drugs that are clinically effective against anxiety disorders modulate the innate defensive behaviour of rodents, suggesting these illnesses reflect altered functioning in brain systems that process threat. This hypothesis is supported in humans by the discovery that the intensity of threat-avoidance behaviour is altered by the benzodiazepine anxiolytic lorazepam. However, these studies used healthy human participants, raising questions as to their validity in anxiety disorder patients, as well as their generalisability beyond GABAergic benzodiazepine drugs. BNC210 is a novel negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor and we recently used functional Magnetic Resonance Imaging to show it reduced amygdala responses to fearful faces in generalised anxiety disorder patients. Here we report the effect of BNC210 on the intensity of threat-avoidance behaviour in 21 female GAD patients from the same cohort. We used the Joystick Operated Runway Task as our behavioural measure, which is a computerised human translation of the Mouse Defense Test Battery, and the Spielberger state anxiety inventory as our measure of state affect. Using a repeated-measures, within-subjects design we assessed the effect of BNC210 at two dose levels versus placebo (300 mg and 2000 mg) upon two types of threat-avoidance behaviour (Flight Intensity and Risk Assessment Intensity). We also tested the effects of 1.5 mg of the benzodiazepine lorazepam as an active control. BNC210 significantly reduced Flight Intensity relative to placebo and the low dose of BNC210 also significantly reduced self-reported state anxiety. Risk Assessment Intensity was not significantly affected. Results show both human defensive behaviour and state anxiety are influenced by cholinergic neurotransmission and there provide converging evidence that this system has potential as a novel target for anxiolytic pharmacotherapy