Beam Energy and Centrality Dependence of Direct-Photon Emission from Ultrarelativistic Heavy-Ion Collisions.

The PHENIX collaboration presents first measurements of low-momentum (0.41  GeV/c) direct-photon yield dN_{γ}^{dir}/dη is a smooth function of dN_{ch}/dη and can be well described as proportional to (dN_{ch}/dη)^{α} with α≈1.25. This scaling behavior holds for a wide range of beam energies at the Relativistic Heavy Ion Collider and the Large Hadron Collider, for centrality selected samples, as well as for different A+A collision systems. At a given beam energy, the scaling also holds for high p_{T} (>5  GeV/c), but when results from different collision energies are compared, an additional sqrt[s_{NN}]-dependent multiplicative factor is needed to describe the integrated-direct-photon yield

Mortality in Peripheral Arterial Disease: A Comparison of Patients Managed by Vascular Specialists and General Practitioners

BACKGROUND: Peripheral arterial disease (PAD) is undertreated by general practitioners (GPs). However, the impact of the suboptimal clinical management is unknown. OBJECTIVE: To assess the mortality rate of PAD patients in relation to the type of physician who provides their care (GP or vascular specialist). DESIGN: Prospective study. SETTING: Primary care practice and academic vascular laboratory. PARTICIPANTS: GP patients (n = 60) were those of the Peripheral Arteriopathy and Cardiovascular Events study (PACE). Patients managed by specialists (n = 82) were consecutive subjects with established PAD who were referred to our vascular laboratory during the enrolment period of the PACE study. MEASUREMENTS: All-cause and cardiovascular mortality. RESULTS: After 32 months of follow-up, specialist management was associated with a lower rate of all-cause mortality (RR = 0.04; 95% CI 0.01–0.34; p = .003) and cardiovascular mortality (RR = 0.07; 95% CI 0.01–0.65; p = .020), after adjustment for patients’ characteristics. Specialists were more likely to use antiplatelet agents (93% vs 73%, p < .001), statins (62% vs 25%, p < .001) and beta blockers (28% vs 3%, p < .001). Survival differences between specialists and GPs disappeared once the use of pharmacotherapies was added to the proportional hazard model. The fully adjusted model showed that the use of statins was significantly associated with a reduced risk of all-cause mortality (RR = 0.02; 95% CI 0.01–0.73, p = .034) and cardiovascular mortality (RR = 0.02; 95% CI 0.01–0.71, p = .033). CONCLUSIONS: Specialist management of patients with symptomatic PAD resulted in better survival than generalist management. This effect appears to be mainly caused by the more frequent use of effective medicines by specialists

Alum Adjuvant Enhances Protection against Respiratory Syncytial Virus but Exacerbates Pulmonary Inflammation by Modulating Multiple Innate and Adaptive Immune Cells

Respiratory syncytial virus (RSV) is well-known for inducing vaccine-enhanced respiratory disease after vaccination of young children with formalin-inactivated RSV (FI-RSV) in alum formulation. Here, we investigated alum adjuvant effects on protection and disease after FIRSV immunization with or without alum in comparison with live RSV reinfections. Despite viral clearance, live RSV reinfections caused weight loss and substantial pulmonary inflammation probably due to high levels of RSV specific IFN-γ+IL4-, IFN-γ-TNF-α+, IFN-γ+ TNF-α- effector CD4 and CD8 T cells. Alum adjuvant significantly improved protection as evidenced by effective viral clearance compared to unadjuvanted FI-RSV. However, in contrast to unadjuvanted FI-RSV, alum-adjuvanted FI-RSV (FI-RSV-A) induced severe vaccine- enhanced RSV disease including weight loss, eosinophilia, and lung histopathology. Alum adjuvant in the FI-RSV-A was found to be mainly responsible for inducing high levels of RSV-specific IFN-γ-IL4+, IFN-γ-TNF-α+ CD4+ T cells, and proinflammatory cytokines IL-6 and IL-4 as well as B220+ plasmacytoid and CD4+ dendritic cells, and inhibiting the induction of IFN-γ+CD8 T cells. This study suggests that alum adjuvant in FI-RSV vaccines increases immunogenicity and viral clearance but also induces atypical T helper CD4+ T cells and multiple inflammatory dendritic cell subsets responsible for vaccine-enhanced severe RSV disease

Effectiveness of Progressive and Resisted and Non-Progressive or Non-Resisted Exercise in Rotator Cuff Related Shoulder Pain: A Systematic Review and Meta-analysis of Randomised Controlled Trials

Objective: Synthesize evidence regarding effectiveness of progressive and resisted or non-progressive and non-resisted exercise compared with placebo or no treatment, in rotator cuff related pain. Data sources: English articles, searched in Cochrane CENTRAL, MEDLINE, EMBASE and CINAHL databases up until May 19, 2020. Methods: Randomized controlled trials in people with rotator cuff related pain comparing either progressive and resisted exercise or non-progressive and non-resisted exercise, with placebo or no treatment were included. Data extracted independently by two authors. Risk of bias appraised with the Cochrane Collaboration tool. Results: Seven trials (468 participants) were included, four trials (271 participants) included progressive and resisted exercise and three trials (197 participants) included non-progressive or non-resisted exercise. There was uncertain clinical benefit for composite pain and function (15 point difference, 95% CI 9 to 21, 100-point scale) and pain outcomes at >6weeks to 6months with progressive and resisted exercise compared to placebo or no treatment (comparison 1). For non-progressive or non-resisted exercise there was no significant benefit for composite pain and function (4 point difference, 95% CI –2 to 9, 100-point scale) and pain outcomes at >6weeks to 6months compared to placebo or no treatment (comparison 2). Adverse events were seldom reported and mild. Conclusions: There is uncertain clinical benefit for all outcomes with progressive and resisted exercise and no significant benefit with non-progressive and non-resisted exercise, versus no treatment or placebo at >6weeks to 6months. Findings are low certainty and should be interpreted with cautio

Hydrodynamic properties of cyclodextrin molecules in dilute solutions

Three well-known representatives of the cyclodextrin family were completely characterized by molecular hydrodynamics methods in three different solvents. For the first time the possibility of an estimation of velocity sedimentation coefficients s between 0.15 and 0.5 S by the numerical solution of the Lamm equation is shown. Comparison of the experimental hydrodynamic characteristics of the cyclodextrins with theoretical calculations for toroidal molecules allows an estimation of the thickness of the solvent layers on the surface of cyclodextrin molecules

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk insT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits

Community Management of Endemic Scabies in Remote Aboriginal Communities of Northern Australia: Low Treatment Uptake and High Ongoing Acquisition

Like many impoverished areas around the world, Aboriginal communities in Australia experience an unacceptably high burden of scabies, skin infections, and secondary complications. Young children are most at risk. Our study investigated scabies in a remote setting with very high rates of skin disease, a high level of household overcrowding, and limited infrastructure for sanitation and preventive health measures. We assessed uptake of scabies treatment and scabies acquisition following provision of treatment by a community-based skin program. In a household where scabies was present, we found that treatment with topical permethrin cream of all close contacts can significantly reduce a susceptible individual's risk of infection. Our findings also demonstrate the challenges of achieving a high level of treatment participation, with limited permethrin use observed among household contacts. This suggests an urgent need for a more practical treatment option. International efforts to reduce childhood morbidity and mortality have demonstrated the efficacy of numerous child health interventions but have also highlighted the deficits in their delivery and implementation. Experiences like this, where the effectiveness of a coordinated local program delivering an efficacious intervention is hampered by poor treatment uptake and ongoing transmission, are an important and timely message for researchers, program managers, and policy-makers

Astrocytic Mechanisms Explaining Neural-Activity-Induced Shrinkage of Extraneuronal Space

Neuronal stimulation causes ∼30% shrinkage of the extracellular space (ECS) between neurons and surrounding astrocytes in grey and white matter under experimental conditions. Despite its possible implications for a proper understanding of basic aspects of potassium clearance and astrocyte function, the phenomenon remains unexplained. Here we present a dynamic model that accounts for current experimental data related to the shrinkage phenomenon in wild-type as well as in gene knockout individuals. We find that neuronal release of potassium and uptake of sodium during stimulation, astrocyte uptake of potassium, sodium, and chloride in passive channels, action of the Na/K/ATPase pump, and osmotically driven transport of water through the astrocyte membrane together seem sufficient for generating ECS shrinkage as such. However, when taking into account ECS and astrocyte ion concentrations observed in connection with neuronal stimulation, the actions of the Na+/K+/Cl− (NKCC1) and the Na+/HCO3− (NBC) cotransporters appear to be critical determinants for achieving observed quantitative levels of ECS shrinkage. Considering the current state of knowledge, the model framework appears sufficiently detailed and constrained to guide future key experiments and pave the way for more comprehensive astroglia–neuron interaction models for normal as well as pathophysiological situations

Sub-Nucleocapsid Nanoparticles: A Nasal Vaccine against Respiratory Syncytial Virus

Background: Bronchiolitis caused by the respiratory syncytial virus (RSV) in infants less than two years old is a growing public health concern worldwide, and there is currently no safe and effective vaccine. A major component of RSV nucleocapsid, the nucleoprotein (N), has been so far poorly explored as a potential vaccine antigen, even though it is a target of protective anti-viral T cell responses and is remarkably conserved between human RSV A and B serotypes. We recently reported a method to produce recombinant N assembling in homogenous rings composed of 10–11 N subunits enclosing a bacterial RNA. These nanoparticles were named sub-nucleocapsid ring structure (N SRS). Methodology and Principal Findings: The vaccine potential of N SRS was evaluated in a well-characterized and widely acknowledged mouse model of RSV infection. BALB/c adult mice were immunized intranasally with N SRS adjuvanted with the detoxified E. coli enterotoxin LT(R192G). Upon RSV challenge, vaccinated mice were largely protected against virus replication in the lungs, with a mild inflammatory lymphocytic and neutrophilic reaction in their airways. Mucosal immunization with N SRS elicited strong local and systemic immunity characterized by high titers of IgG1, IgG2a and IgA anti-N antibodies, antigen-specific CD8+ T cells and IFN-c-producing CD4+ T cells. Conclusions/Significance: This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV