Elevated Depressive Symptoms and Incident Stroke in Hispanic, African-American, and White Older Americans

Although depressive symptoms have been linked to stroke, most research has been in relatively ethnically homogeneous, predominantly white, samples. Using the United States based Health and Retirement Study, we compared the relationships between elevated depressive symptoms and incident first stroke for Hispanic, black, or white/other participants (N = 18,648) and estimated the corresponding Population Attributable Fractions. The prevalence of elevated depressive symptoms was higher in blacks (27%) and Hispanics (33%) than whites/others (18%). Elevated depressive symptoms prospectively predicted stroke risk in the whites/other group (HR = 1.53; 95% CI: 1.36–1.73) and among blacks (HR = 1.31; 95% CI: 1.05–1.65). The HR was similar but only marginally statistically significant among Hispanics (HR = 1.33; 95% CI: 0.92–1.91). The Population Attributable Fraction, indicating the percent of first strokes that would be prevented if the incident stroke rate in those with elevated depressive symptoms was the same as the rate for those without depressive symptoms, was 8.3% for whites/others, 7.8% for blacks, and 10.3% for Hispanics

Evolutionary consequences of intra-patient phage predation on microbial populations

The impact of phage predation on bacterial pathogens in the context of human disease is not currently appreciated. Here, we show that predatory interactions of a phage with an important environmentally transmitted pathogen, Vibrio cholerae, can modulate the evolutionary trajectory of this pathogen during the natural course of infection within individual patients. We analyzed geographically and temporally disparate cholera patient stool samples from Haiti and Bangladesh and found that phage predation can drive the genomic diversity of intra-patient V. cholerae populations. Intra-patient phage-sensitive and phage-resistant isolates were isogenic except for mutations conferring phage resistance, and moreover, phage-resistant V. cholerae populations were composed of a heterogeneous mix of many unique mutants. We also observed that phage predation can significantly alter the virulence potential of V. cholerae shed from cholera patients. We provide the first molecular evidence for predatory phage shaping microbial community structure during the natural course of infection in humans. DOI: http://dx.doi.org/10.7554/eLife.03497.00

Community-based in situ simulation: bringing simulation to the masses

Simulation-based methods are regularly used to train inter-professional groups of healthcare providers at academic medical centers (AMC). These techniques are used less frequently in community hospitals. Bringing in-situ simulation (ISS) from AMCs to community sites is an approach that holds promise for addressing this disparity. This type of programming allows academic center faculty to freely share their expertise with community site providers. By creating meaningful partnerships community-based ISS facilitates the communication of best practices, distribution of up to date policies, and education/training. It also provides an opportunity for system testing at the community sites. In this article, we illustrate the process of implementing an outreach ISS program at community sites by presenting four exemplar programs. Using these exemplars as a springboard for discussion, we outline key lessons learned discuss barriers we encountered, and provide a framework that can be used to create similar simulation programs and partnerships. It is our hope that this discussion will serve as a foundation for those wishing to implement community-based, outreach ISS

Prevalence of and factors associated with late diagnosis of HIV in Malawi, Zambia, and Zimbabwe: Results from population-based nationally representative surveys

Introduction Late diagnosis of HIV (LD) increases the risk of morbidity, mortality, and HIV transmission. We used nationally representative data from population-based HIV impact assessment (PHIA) surveys in Malawi, Zambia, and Zimbabwe (2015–2016) to characterize adults at risk of LD and to examine associations between LD and presumed HIV transmission to cohabiting sexual partners. Methods We estimated the prevalence of LD, defined as CD4 count <350 cells/μL, among adults newly diagnosed with HIV during the surveys and odds ratios for associated factors. We linked newly diagnosed adults (index cases) to their household sexual partners and calculated adjusted odds ratios for associations between LD of the index case, viral load of the index case, and duration of HIV exposure in the relationship, and the HIV status of the household sexual partner. Results Of 1,804 adults who were newly diagnosed with HIV in the surveys, 49% (882) were diagnosed late. LD was associated with male sex, older age, and almost five times the odds of having an HIV-positive household sexual partner (adjusted odds ratio [aOR], 4.65 [95% confidence interval: 2.56–8.45]). Longer duration of HIV exposure in a relationship and higher viral load of the index case were both independently associated with higher odds of having HIV-positive household sexual partners. Individuals with HIV exposure of more than 5 years had more than three times (aOR 3.42 [95% CI: 1.63–7.18]) higher odds of being HIV positive than those with less than 2 years HIV exposure. The odds of being HIV positive were increased in individuals who were in a relationship with an index case with a viral load of 400–3499 copies/mL (aOR 4.06 [95% CI 0.45–36.46]), 3,500–9,999 copies/mL (aOR 11.32 [95% CI: 4.08–31.39]), 10,000–49,999 copies/mL (aOR 17.07 [95% CI: 9.18–31.72]), and ≥50,000 copies/mL (aOR 28.41 [95% CI: 12.18–66.28]) compared to individuals who were in a relationship with an index case with a viral load of <400 copies/mL. Conclusions LD remains a challenge in Southern Africa and is strongly associated with presumed HIV transmission to household sexual partners. Our study underscores the need for earlier HIV diagnosis, particularly among men and older adults, and the importance of index testing

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Comparison of Robotics, Functional Electrical Stimulation, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction After Stroke: A Randomized Controlled Trial

Objective To compare response to upper-limb treatment using robotics plus motor learning (ML) versus functional electrical stimulation (FES) plus ML versus ML alone, according to a measure of complex functional everyday tasks for chronic, severely impaired stroke survivors. Design Single-blind, randomized trial. Setting Medical center. Participants Enrolled subjects (N=39) were \u3e1 year post single stroke (attrition rate=10%; 35 completed the study). Interventions All groups received treatment 5d/wk for 5h/d (60 sessions), with unique treatment as follows: ML alone (n=11) (5h/d partial- and whole-task practice of complex functional tasks), robotics plus ML (n=12) (3.5h/d of ML and 1.5h/d of shoulder/elbow robotics), and FES plus ML (n=12) (3.5h/d of ML and 1.5h/d of FES wrist/hand coordination training). Main Outcome Measures Primary measure: Arm Motor Ability Test (AMAT), with 13 complex functional tasks; secondary measure: upper-limb Fugl-Meyer coordination scale (FM). Results There was no significant difference found in treatment response across groups (AMAT: P≥.584; FM coordination: P≥.590). All 3 treatment groups demonstrated clinically and statistically significant improvement in response to treatment (AMAT and FM coordination: P≤.009). A group treatment paradigm of 1:3 (therapist/patient) ratio proved feasible for provision of the intensive treatment. No adverse effects. Conclusions Severely impaired stroke survivors with persistent (\u3e1y) upper-extremity dysfunction can make clinically and statistically significant gains in coordination and functional task performance in response to robotics plus ML, FES plus ML, and ML alone in an intensive and long-duration intervention; no group differences were found. Additional studies are warranted to determine the effectiveness of these methods in the clinical setting

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data

Ferrets as models for influenza virus transmission studies and pandemic risk assessments

The ferret transmission model is extensively used to assess the pandemic potential of emerging influenza viruses, yet experimental conditions and reported results vary among laboratories. Such variation can be a critical consideration when contextualizing results from independent risk-assessment studies of novel and emerging influenza viruses. To streamline interpretation of data generated in different laboratories, we provide a consensus on experimental parameters that define risk-assessment experiments of influenza virus transmissibility, including disclosure of variables known or suspected to contribute to experimental variability in this model, and advocate adoption of more standardized practices. We also discuss current limitations of the ferret transmission model and highlight continued refinements and advances to this model ongoing in laboratories. Understanding, disclosing, and standardizing the critical parameters of ferret transmission studies will improve the comparability and reproducibility of pandemic influenza risk assessment and increase the statistical power and, perhaps, accuracy of this model

Cholesterol and Lipoprotein Dynamics in a Hibernating Mammal

Hibernating mammals cease feeding during the winter and rely primarily on stored lipids to fuel alternating periods of torpor and arousal. How hibernators manage large fluxes of lipids and sterols over the annual hibernation cycle is poorly understood. The aim of this study was to investigate lipid and cholesterol transport and storage in ground squirrels studied in spring, summer, and several hibernation states. Cholesterol levels in total plasma, HDL and LDL particles were elevated in hibernators compared with spring or summer squirrels. Hibernation increased plasma apolipoprotein A-I expression and HDL particle size. Expression of cholesterol 7 alpha-hydroxylase was 13-fold lower in hibernators than in active season squirrels. Plasma triglycerides were reduced by fasting in spring but not summer squirrels. In hibernators plasma β-hydroxybutyrate was elevated during torpor whereas triglycerides were low relative to normothermic states. We conclude that the switch to a lipid-based metabolism during winter, coupled with reduced capacity to excrete cholesterol creates a closed system in which efficient use of lipoproteins is essential for survival

A Soluble Form of the High Affinity IgE Receptor, Fc-Epsilon-RI, Circulates in Human Serum

Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI), the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum