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Alteplase for Posterior Circulation Ischemic Stroke at 4.5 to 24 Hours

The conserved HIV-1 spacer peptide 2 triggers matrix lattice maturation

Abstract The virus particles of human immunodeficiency virus type 1 (HIV-1) are released in an immature, non-infectious form. Proteolytic cleavage of the main structural polyprotein Gag into functional domains induces rearrangement into mature, infectious virions. In immature virus particles, the Gag membrane-binding domain, MA, forms a hexameric protein lattice that undergoes structural transition, following cleavage, into a distinct, mature MA lattice 1 . The mechanism of MA lattice maturation is unknown. Here we show that released spacer peptide 2 (SP2), a conserved peptide of unknown function situated about 300 residues downstream of MA, binds MA to induce structural maturation. By high-resolution in-virus structure determination of MA, we show that MA does not bind lipid into a side pocket as previously thought 1 , but instead binds SP2 as an integral part of the protein–protein interfaces that stabilize the mature lattice. Analysis of Gag cleavage site mutants showed that SP2 release is required for MA maturation, and we demonstrate that SP2 is sufficient to induce maturation of purified MA on lipid monolayers in vitro. SP2-triggered MA maturation correlated with faster fusion of virus with target cells. Our results reveal a new, unexpected interaction between two HIV-1 components, provide a high-resolution structure of mature MA, establish the trigger of MA structural maturation and assign function to the SP2 peptide.

Telemedicine interventions for improving antibiotic stewardship and prescribing: A systematic review

The global antibiotic resistance crisis necessitates optimized stewardship programs, with telemedicine emerging as a promising delivery strategy. This systematic review evaluated the effectiveness of telemedicine interventions in improving antibiotic stewardship across clinical settings. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched seven databases from January 2010 to July 2024. Two independent reviewers assessed studies using Risk of Bias in Non-randomized Studies (ROBINS-I) and Cochrane Risk of Bias 2.0 tools, with evidence certainty evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty-one studies met inclusion criteria (10 observational, 8 quasi-experimental, 2 Randomized Controlled Trials [RCTs], 1 mixed-methods), predominantly from the United States (57.0%, n = 12). Among studies reporting antibiotic use outcomes (52.4%, n = 11), 90.9% demonstrated significant reductions ranging from 5.3% to 62.7%, with the highest-quality evidence showing a 28% reduction (95% Confidence Interval [CI]: 22-34%). Guideline adherence studies (57.1%, n = 12) showed acceptance rates of 67.7% to 98%, with comparable effectiveness between telemedicine and in-person consultation (79.1% vs 80.4%, p = 0.36). Prescribing rate outcomes (38.1%, n = 8) revealed setting-dependent variations: inpatient implementations demonstrated significant reductions (Relative Risk [RR] 0.68; 95% CI: 0.63-0.75), while outpatient findings showed mixed results. Quality assessment revealed predominantly low risk of bias [ROB] (66.7%, n = 14). These findings suggest that telemedicine effectively improves antibiotic stewardship compared to traditional care models, particularly in hospital settings, while outpatient applications demonstrated variable effectiveness. This review was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023454663).

NEJM Outbreaks Update — H5N1: A View from the States

A novel use of Stereo Baited Remote Underwater Video and Drop-Down Video for biodiversity and marine landscape mapping and prediction

To make the best-informed decisions on managing marine resources whilst also restoring biodiversity, the creation and analysis of benthic maps is highly valuable. This study focuses on benthic mapping to study patch - and landscape - level processes affecting epifauna and demersal species using Stereo Baited Remote Underwater Video (SBRUV) and Drop-Down Video (DDV) surveys. Surveys were conducted within the South Arran Marine Protected Area between 2013–2019 and yielded 554 SBRUV data points and 333 DDV data points. These data were processed to determine proportional coverage of substrata and kriged to produce benthic maps. From this it was possible to estimate the patch scale of substrata to gain a more detailed understanding of the marine landscape, composition structure, and epibenthic biodiversity. The resulting validated maps allowed the number of substrata patches and patch characteristics such as area and perimeter-to-area ratio to be calculated to support management and understanding of the value of this seascapes for benthic and demersal biodiversity. Our approach allowed for the identification of areas of higher biodiversity that may assist during mapping of Marine Protected Areas’ (MPA) vulnerable features. These methods should provide better information about site condition and ecosystem service provision than existing methods.

Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons

Mendelian randomization study showed no causality between metformin treatment and polycystic ovary syndrome

Background Despite previous clinical studies providing some evidence of an association between metformin treatment and polycystic ovary syndrome(PCOS), these findings remain controversial. To investigate whether the association reflect causality, a two-sample Mendelian randomization (MR) method was conducted. Methods Data from genome-wide association studies were analyzed, with the exposure factor being metformin and the outcome variable being PCOS. The inverse variance weighted(IVW) was used as the primary method for MR analysis. In addition, MR–Egger, weighted median, heterogeneity tests, and sensitivity analyses were performed. Results The initial and validation MR analyses indicated that genetically predicted metformin treatment had no effects on PCOS. Sensitivity analyses provided additional confirmation of the reliability of the MR results. Conclusions Our two-sample MR analysis did not find genetic evidence supporting a significant association between metformin treatment and PCOS.

The Genetic Architecture of Congenital Diarrhea and Enteropathy

Machine learning for automated electrical penetration graph analysis of aphid feeding behavior: Accelerating research on insect-plant interactions

The electrical penetration graph (EPG) is a well-known technique that provides insights into the feeding behavior of insects with piercing-sucking mouthparts, mostly hemipterans. Since its inception in the 1960s, EPG has become indispensable in studying plant-insect interactions, revealing critical information about host plant selection, plant resistance, virus transmission, and responses to environmental factors. By integrating the plant and insect into an electrical circuit, EPG allows researchers to identify specific feeding behaviors based on their distinctive waveform patterns. However, the traditional manual analysis of EPG waveform data is time-consuming and labor-intensive, limiting research throughput. This study presents a novel Machine Learning (ML) approach to automate the annotation of EPG signals. We rigorously evaluated six diverse ML models, including neural networks, tree-based models, and logistic regression, using an extensive dataset from multiple aphid feeding experiments. Our results demonstrate that a Residual Network (ResNet) architecture achieved the highest overall waveform classification accuracy of 96.8% and highest segmentation overlap rate of 84.4%, highlighting the potential of ML for accurate and efficient EPG analysis. This automated approach promises to accelerate research in this field significantly and broaden insights into insect-plant interactions, showcasing the power of computational techniques for insect biological research. The source code for all experiments conducted within this study is publicly available at https://github.com/HySonLab/ML4Insects.

Working at Cross-PURPOSEs to Ending HIV

Monitoring sodium content in packaged foods sold in the Americas and compliance with the updated regional sodium reduction targets

Background Sodium reduction is a cost-effective measure to prevent noncommunicable diseases. The World Health Organization (WHO) established a target of a 30% relative reduction in mean population intake of sodium by 2025. The Pan American Health Organization (PAHO) published sodium reduction targets (SRTs) for packaged foods in 2015, expanding and updating the targets in 2021 to help Member States with its efforts in reducing population sodium intake. Objective This study examined the current sodium levels in packaged foods among five countries in the Americas and monitored cross-sectional and longitudinal compliance with the sodium targets from 2015 to 2022. Methods Food labels were systematically collected from the main supermarkets in five countries in the Americas region in 2022. Sodium levels per 100g and per kcal for collected food labels in 16 PAHO categories and 75 subcategories were analyzed and compared against the updated SRTs. Further analysis of three countries that have longitudinal data for 2015–2016, 2017–2018 and 2022 was conducted to compare sodium per 100 g against the 2015 SRTs. Results A total of 25,569 food items were analyzed. Overall, ‘processed meat and poultry’ had the highest sodium levels, although there were large variations within categories. 47% and 45% of products met the sodium per 100g and per kcal 2022 SRTs, respectively. Peru had the highest compliance, whereas Panama had the lowest for both targets. Among Argentina, Costa Rica and Peru, the proportion of foods meeting the 2015 PAHO lower targets were 48, 53 and 61% for 2015–2016, 2017–2018 and 2022, respectively (p < 0.001). Conclusions This study showed that around half of the examined foods met their respective SRTs and there have been small improvements in compliance over time. Further efforts are required to reach the WHO’s global sodium reduction goal by 2025, such as implementation of mandatory SRTs and front-of-pack labelling regulations.

Application Overload — A Call to Reduce the Burden of Applying to Medical School

Possible sarcopenia and depression among middle-aged and older adults in China: A 9-year longitudinal survey

Possible sarcopenia (PS) and depression are prevalent among middle-aged and older adults. However, few studies have evaluated the causal association between depression and PS, as well as its components. This study conducted both cross-sectional and longitudinal analyses to explore the relationship between PS and depression in a population aged 45 and oledr. We evaluated the association between PS and its components with depression using data from the China Health and Retirement Longitudinal Study (CHARLS). PS was assessed according to the Asian Working Group for sarcopenia gudielines established in 2019 (AWGS 2019). Depression was measured by the validated 10-item Center for Epidemiological Studies Depression Scale (CES-D.10), with a cut-off score of 12 or higher indicating the presence of depression. 10,058 participants included in cross-sectional study and 5,726 participants without depression from the same cohort in 2011 were followed through 2020. Logistic regression and Cox proportional hazards models were employed to assess the association between PS and its components with depression. Restricted cubic spline (RCS) model was utilized to evaluate dose-response relationshipbetween muscle strength and physical performance with depression, and subgroup analyses were performed to validate the robustness of the findings. Cross-sectional analysis revealed that the prevalence of PS among middle-aged and older adults was 32.84% (3,303/10,058). Both PS (OR:1.47,95%CI:1.34–1.63), low muscle strength (LMS) (OR:1.46,95%CI:1.24–1.71) and low physical performance (LPP) (OR:1.45,95%CI:1.31–1.61) exhibited higher odds of depression after adjusting covariates. 1515 cases (26.46%) of incident depression were identified during the 9-years follow-up. Subjects with PS (HR:1.10,95%CI:1.01–1.19), LMS (HR:1.16,95%CI:1.01–1.34) and LPP (HR:1.08,95%CI:1.01–1.18) were at an elevated risk of new-onset depression compared to those without these conditions. The RCS analysis demonstrated a non-linear relationship between muscle strength and physical performance with depression (p > 0.05). Participants aged 50–59, married, with education below middle school, living in rural areas, non-smokers or non-drinkers, sleeping less than 8 hours, and classified as obese exhibited an increased risk in subgroup analysis. (all p <  0.05). PS, LMS and LPP were indentified as independent risk factors for new-onset depression. It is essential to assess muscle strength and physical performance in community-dwelling middle-aged and older adults using simple and feasible objective measures to enhance depression screening.

Modest Blood Pressure Increase with Age in Adults with Down’s Syndrome

The evolution of bone-eating worm diversity in the Upper Cretaceous Chalk Group of the United Kingdom

The bone-eating worm Osedax is today a member of the highly adapted invertebrate assemblages associated with whale carcasses on the ocean floor. The worm has also been found in a variety of other vertebrates in marine environments. Osedax borings are represented by the trace fossil Osspecus, which has been identified in fossil whales and marine reptiles, with the earliest occurrence in the Albian. In studies of present-day whale bones it has been found that individual species of Osedax create distinct boring morphologies. The diversity of boring geometries therefore provides a proxy for species diversity that can be applied to the fossil record to better understand the diversity, ecology, and evolution of extinct Osedax species. We examined marine reptile fossils from the Upper Cretaceous Chalk Group of the United Kingdom, and found five previously undocumented boring morphologies. These results, coupled with a re-examination of previous records of Osspecus, led to the naming of seven new ichnospecies. Using nannofossil biostratigraphy from the chalk, we constrained the ages of these occurrences and found a high species diversity in the early Late Cretaceous, indicating either a rapid diversification or an earlier origin for Osedax than previously estimated. Furthermore, we recognise five Cretaceous ichnospecies that are also found in the Cenozoic, three of which are also found in present-day whale bones.

Association between Wealth and Mortality in the United States and Europe

The supplemental nutrition assistance program and older adults: A scoping review protocol

Objective The objective of this scoping review is to describe the scope of original published research on SNAP and older adults. Introduction Food insecurity among older adults in the United States is a significant public health issue. Participation in the Supplemental Nutrition Assistance Program (SNAP), the largest nutrition assistance program in the United States, by older adults is lower than the overall participation rate. Inclusion criteria This scoping review will include original research focused on older adults (aged 60 years and older) and participation in SNAP. Studies should address at least one of the following: examining one or more outcomes related to participation in SNAP, facilitators or barriers to SNAP participation, and/or evaluation of a program, policy or other strategy for influencing SNAP participation. Methods Databases to be searched include PubMed, Scopus, CINAHL, and ProQuest. Sciwheel will be used for deduplicating references that will be imported into Covidence for screening and extracting data. Two independent reviewers will screen titles/abstracts followed by full-text articles to assess whether articles meet inclusion criteria and then complete a data extraction template for each included article. A third reviewer will resolve any discrepancies. The findings will be summarized and presented in tables and narrative form.

Cervical Cancer

Study protocol: LIAM Mc trial (Linking In with Advice and supports for Men impacted by Metastatic cancer)

Background The significant increase in cancer survivorship rates necessitates a comprehensive, multidisciplinary approach to supportive care services. This study seeks to assess the feasibility of introducing a Men’s Health Initiative supportive care intervention program in Ireland. Methods This is a single-arm feasibility study involving a 12-week men’s cancer survivorship programme alongside routine follow-up care in patients with advanced genitourinary malignancies. Men with advanced/metastatic genitourinary cancer (including prostate, kidney, urothelial tract, testicular or penile cancer), are eligible to enrol, with a target of 72 participants over a 2-year period. The intervention programme entails a twice-weekly physiotherapy-led exercise programme, along with dietetics, nursing, and psychosocial components, and regular signposting to additional available services. A Pilot Phase involving analysis of data from the first group of 6 participants to complete the programme is planned, before an Expansion Phase. Assessments will occur at baseline, on completion of the 12-week intervention, and 3 months post-intervention, and will include analyses of exercise/activity levels, body composition, muscle strength, psychological wellbeing, quality of life and resources utilised. The primary endpoints are to determine the feasibility and acceptability of introducing a men’s cancer survivorship intervention programme into routine follow-up care in patients with advanced genitourinary malignancies. Secondary endpoints include impact of the intervention programme on quality of life, cancer-related fatigue, maintenance of weight, changes in body composition and changes in dietary intake and diet quality over the study period, as well as self-care agency and its relationship to quality of life and symptoms experienced. A qualitative process evaluation will be undertaken to explore participants’ experiences, while an economic analysis will examine the healthcare resource utilization and costs associated with the intervention. The trial was peer-reviewed by the Irish Cancer Society. Discussion The programme described in this protocol provides a supportive and safe environment for the introduction of self-care interventions using a small group-based format supported by individualised counselling according to the participant’s identified needs. The development and implementation of future supportive care programmes for men’s cancer survivorship will be guided by the findings of this study. Trial registrartion ClinicalTrials.gov NCT05946993

A “Hot” Cardiomyopathy