The severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) omicron sub-variants in Bangladesh cause mild COVID-19 and associate with similar antibody responses irrespective of natural infection or vaccination history.

Objective: Genomic surveillance and seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) in Bangladesh is paramount for COVID-19 pandemic preparedness yet lagging the high-income countries due to limited resources. Methods: SARS-CoV-2 variants, COVID-19 symptoms, and serology were prospectively evaluated in a cross-sectional study of Bangladeshi adults testing RT-PCR positive in 2021 and 2022. Results: SARS CoV-2 Omicron variants of asymptomatic or mild COVID-19 in 2022 replaced Delta variant infections requiring hospitalization and oxygen support. The omicron XBB became predominant in July 2022 and associated with cough, headache or body ache and loss of smell; 47 of 68 (69 %), 30 of 68 (44 %) and 27 of 68 (40 %) respectively at higher frequency than BA.1/BA.2; 16 of 88 (18 %), 13 of 88 (15 %) and 0 of 88 (0 %) p < 0.01, p < 0.01 and p < 0.0001. Linear regression analysis reveals no associations between the number of previous infections and the number of symptoms, r = -0.084, p = 0.68. The anti-nucleoprotein (N)-protein IgG post COVID-19 and anti-Spike (S) protein IgG post-COVID-19 vaccination were similar between BA.2, BA.4/BA.5 and XBB and significantly lower than the levels in delta variant infections (p < 0.001). Conclusions: Omicron XBB subvariants emerged in Bangladesh two months prior to previous reports and include unique patterns of S-protein mutations not assigned in PANGO lineage. The SARS CoV-2 omicron break-through infections persist in the presence of sustained antibody responses and vaccinations, underscoring the importance of molecular surveillance in low-income countries.

Application of a Heuristic Framework for Multilevel Interventions to Eliminate the Impact of Unjust Social Processes and Other Harmful Social Determinants of Health.

There is consensus about the importance of developing a strong cadre of effective multilevel interventions to eliminate the impacts of unjust social processes, such as structural racism and other harmful social determinants of health (SDOH), on health inequities in the USA. However, the available cadre of rigorously evaluated evidence-based interventions for SDOH mitigation remains underdeveloped relative to the magnitude of historic and current health inequities. The proposed manuscript addresses this gap in two ways: first, by introducing a heuristic framework to inform decisions in multilevel intervention development, study design, and selection of analytic methods and, second, by providing a roadmap for future applications of the framework in multilevel intervention research through an exemplar application using the ongoing NIH-funded evaluation study of the Nurse-Community-Family Partnership (NCFP) intervention. NCFP leverages individual, family, institutional, and system factors to shape COVID-19 mitigation outcomes at the individual and household levels. NCFP takes an approach informed by the heuristic framework to addressing and mitigating unjust social processes and other harmful SDOH. We discuss the application of a two-arm parallel explanatory group randomized trial to evaluate the efficacy of NCFP in improving the primary (COVID-19 testing uptake) and secondary (adoption of COVID-19 control measures, COVID-19 vaccine uptake, mutual aid capacity, etc.) outcomes at the individual and household levels. The analysis approach relies on random-intercept models, and we calculate the variance partitioning coefficient to estimate the extent to which household- and individual-level variables contribute to the outcome, allowing examination of NCFP effects at multiple levels.

Paternal Perspectives on Latino and Black Sons' Readiness for Sex and Condom Guidance: A Mixed Methods Study.

PURPOSE: Although a large proportion of males in the United States become sexually active during high school, condom use is decreasing and contributing to negative sexual health outcomes. Fathers are influential in promoting adolescent male sexual health; however, factors that shape fathers' decisions about when to discuss condom use with their sons remain understudied. We examined paternal perceptions of adolescent males' readiness for sex relative to fathers providing guidance for condom use in Latino and Black families. METHODS: We recruited 191 Latino and Black males aged 15-19 years and their fathers in the South Bronx, New York City. Dyads completed surveys, and a subset of fathers participated in audio-recorded sessions with a father coach, which included conversations about adolescent male condom use. A sequential explanatory mixed methods design identified adolescent male developmental predictors for paternal guidance for condom use and explored how fathers perceive their sons' readiness for sex. RESULTS: The quantitative findings indicate that paternal perception of their sons' readiness for sex is an important predictor of providing guidance for condom use, and that fathers consider other factors (beyond age and perceived sexual activity) in understanding their sons' developmental readiness for sex. The qualitative findings provide insights into these additional factors, which should be considered when engaging fathers in primary care around issues of adolescent male condom use. CONCLUSIONS: Fathers' perception of their sons' readiness for sex is a predictor of providing condom guidance. We provide practical suggestions for engaging fathers in primary care to promote correct and consistent condom use by adolescent males.

Is the USA on track to end the HIV epidemic?

Despite progress in reducing new HIV infections in the USA, publicly available data suggest that new HIV infections continue to occur at an alarming rate. In this Viewpoint, we highlight the regularity with which the existing systems for HIV prevention and treatment delivery in the USA fail and the clearly inequitable effect of the systems' failure among several priority populations of the Ending the HIV Epidemic (EHE) initiative. Existing data cast doubt on whether the current EHE efforts will suffice to achieve its 2030 goal of reducing annual new HIV infections to fewer than 3000. We outline future directions in four priority areas to regain lost ground in pursuit of the 2030 EHE goals: reducing the stigma affecting people living with and most at risk of HIV; broadening the HIV workforce; mitigating harmful social determinants of health; and recommitting and reinvesting in health in the USA more broadly.

Paternal Communication and Sexual Health Clinic Visits Among Latino and Black Adolescent Males With Resident and Nonresident Fathers.

PURPOSE: Latino and Black adolescent males experience sexual health inequities, and their engagement in sexual health services remains low. Parents shape adolescent sexual health behavior and other youth outcomes. However, the role of Latino and Black fathers in promoting male adolescent sexual health is understudied, in part because about one in four fathers resides apart from their children and nonresident fathers are presumed to be less influential. We examined associations of paternal communication with sexual health service use and perceived paternal role modeling among Latino and Black adolescent males with resident and nonresident fathers. METHODS: We recruited 191 Latino and Black adolescent males aged 15-19 years and their fathers in the South Bronx, New York City, using area sampling methods; dyads completed surveys. We estimated bivariate and adjusted associations of paternal communication with adolescent male sexual health service use and perceived paternal role modeling using logistic and linear regressions. Effect measure modification by paternal residence was assessed. RESULTS: A unit increase on a five-point paternal communication scale was associated with approximately twice and 1.7 times the likelihood of clinical sexual health service use during adolescent males' lifetime and in the past 3 months, respectively; there was no significant effect measure modification by paternal residence. Paternal communication was associated with increased levels of perceived paternal role modeling and usefulness of paternal advice, with stronger associations for nonresident fathers. DISCUSSION: Both resident and nonresident Latino and Black fathers warrant greater consideration as partners in promoting male adolescent sexual health service use.

Nurse-led approaches to address social determinants of health and advance health equity: A new framework and its implications.

BACKGROUND: The U.S. health care system is burdened by inefficiencies, longstanding health inequities, and unstainable costs. Within the nursing profession and the broader health care sector, there is growing recognition of the need for a paradigm shift that addresses persistent structural problems and advances health equity. PURPOSE: Despite evidence of the importance of the social determinants of health (SDOH) in shaping inequitable health outcomes, practical tools for applying SDOH theory in the development of effective nurse-led programs to mitigate harmful SDOH remain scarce. METHODS: We synthesize extant SDOH literature into a heuristic framework for conceptualizing core SDOH mechanisms, constructs, and principles. FINDINGS: To illustrate how nurse scientists can use the framework to guide the development of programs for SDOH mitigation, we outline a three-step exemplar application to the U.S. Latino HIV epidemic. DISCUSSION: Our framework can inform a paradigm shift toward nurse-led, multi-level SDOH mitigation across practice, education, and research.

Conceptualizing the Mechanisms of Social Determinants of Health: A Heuristic Framework to Inform Future Directions for Mitigation.

Policy Points A large body of scientific work examines the mechanisms through which social determinants of health (SDOH) shape health inequities. However, the nuances described in the literature are infrequently reflected in the applied frameworks that inform health policy and programming. We synthesize extant SDOH research into a heuristic framework that provides policymakers, practitioners, and researchers with a customizable template for conceptualizing and operationalizing key mechanisms that represent intervention opportunities for mitigating the impact of harmful SDOH. In light of scarce existing SDOH mitigation strategies, the framework addresses an important research-to-practice translation gap and missed opportunity for advancing health equity. CONTEXT: The reduction of health inequities is a broad and interdisciplinary endeavor with implications for policy, research, and practice. Health inequities are most often understood as associated with the social determinants of health (SDOH). However, policy and programmatic frameworks for mitigation often rely on broad SDOH domains, without sufficient attention to the operating mechanisms, and effective SDOH mitigation strategies remain scarce. To expand the cadre of effective SDOH mitigation strategies, a practical, heuristic framework for policymakers, practitioners, and researchers is needed that serves as a roadmap for conceptualizing and targeting the key mechanisms of SDOH influence. METHODS: We conduct a critical review of the extant conceptual and empirical SDOH literature to identify unifying principles of SDOH mechanisms and to synthesize an integrated framework for conceptualizing such mechanisms. FINDINGS: We highlight eight unifying principles of SDOH mechanisms that emerge from landmark SDOH research. Building on these principles, we introduce and apply a conceptual model that synthesizes key SDOH mechanisms into one organizing, heuristic framework that provides policymakers, practitioners, and researchers with a customizable template for conceptualizing and operationalizing the key SDOH mechanisms that represent intervention opportunities to maximize potential impact for mitigating a given health inequity. CONCLUSIONS: Our synthesis of the extant SDOH research into a heuristic framework addresses a scarcity of peer-reviewed organizing frameworks of SDOH mechanisms designed to inform practice. The framework represents a practical tool to facilitate the translation of scholarly SDOH work into evidence-based and targeted policy and programming. Such tools designed to close the research-to-practice translation gap for effective SDOH mitigation are sorely needed, given that health inequities in the United States and in many other parts of the world have widened over the past two decades.

Evaluating the efficacy of an online, family-based intervention to promote adolescent sexual health: a study protocol for a randomized controlled trial.

BACKGROUND: Adolescents in the U.S. experience significant negative sexual health outcomes, representing a public health priority in the U.S. Research shows that while parents play an influential role in shaping adolescent sexual behavior, surprisingly few programs engage parents in existing programming. Moreover, most efficacious parent-based programs focus on young adolescents, and few utilize delivery mechanisms that facilitate broad reach and scale-up. To address these gaps, we propose to test the efficacy of an online-delivered, parent-based intervention adapted to address both younger and older adolescent sexual risk behavior. METHODS: In this parallel, two-arm, superiority randomized controlled trial (RCT), we propose to evaluate Families Talking Together Plus (FTT+), an adaptation of an existing and efficacious FTT parent-based intervention, in shaping sexual risk behavior among adolescents aged 12-17 and delivered via a teleconferencing application (e.g., Zoom). The study population will include n=750 parent-adolescent dyads recruited from public housing developments in the Bronx, New York. Adolescents will be eligible if they are between the ages of 12 and 17 years of age, self-report as Latino and/or Black, have a parent or primary caregiver, and are South Bronx residents. Parent-adolescent dyads will complete a baseline survey, after which they will be assigned to either the FTT+ intervention condition (n=375) or the passive control condition (n=375) in a 1:1 allocation ratio. Parents and adolescents in each condition will complete follow-up assessments 3 and 9 months post-baseline. The primary outcomes will include sexual debut and ever sex, and the secondary outcomes will include the frequency of sex acts, number of lifetime sexual partners, number of unprotected sex acts, and linkage to health and educational/vocational services in the community. We will utilize intent-to-treat analyses of 9-month outcomes and single degree of freedom contrasts comparing the intervention to the control group for primary and secondary outcomes. DISCUSSION: The proposed evaluation and analysis of the FTT+ intervention will address gaps in the current cadre of parent-based programs. If efficacious, FTT+ would represent a model for scale-up and adoption of parent-based approaches designed to address adolescent sexual health in the U.S. TRIAL REGISTRATION: ClinicalTrials.gov NCT04731649. Registered on February 1, 2021.

Clinical Presentation of COVID-19 and Antibody Responses in Bangladeshi Patients Infected with the Delta or Omicron Variants of SARS-CoV-2.

The clinical presentation of COVID-19 and the specific antibody responses associated with SARS-CoV-2 variants have not been investigated during the emergence of Omicron variants in Bangladesh. The Delta and Omicron variants were identified by post-PCR melting curve analysis of the spike (S) protein receptor binding domain amplicons. Anti-S-protein immunoglobulin-G anti-nucleocapsid (N)-protein immunoglobulin-G and immunoglobulin-A levels were measured by ELISA. The Delta variant was found in 40 out of 40 (100%) SARS-CoV-2 RT-PCR positive COVID-19 patients between 13 September and 23 October 2021 and Omicron variants in 90 out of 90 (100%) RT-PCR positive COVID-19 patients between 9 January and 10 February 2022. The Delta variant associated with hospitalization (74%, 80%, and 40%) and oxygen support (60%, 57%, and 40%) in the no vaccine, dose-1, and dose-2 vaccinated cases, respectively, whereas the Omicron COVID-19 required neither hospitalization nor oxygen support (0%, p < 0.0001). Fever, cough, and breathlessness were found at a significantly higher frequency among the Delta than Omicron variants (p < 0.001). The viral RNA levels of the Delta variant were higher than that of the Omicron variants (Ct median 19.9 versus 23.85; p < 0.02). Anti-spike protein immunoglobulin-G and anti-N-protein immunoglobulin-G within 1 week post onset of Delta variant COVID-19 symptoms indicate prior SARS-CoV-2 infection. The Delta variant and Omicron BA.1 and BA.2 breakthrough infections in the Dhaka region, at 240 days post onset of COVID-19 symptoms, negatively correlated with the time interval between the second vaccine dose and serum sampling. The findings of lower anti-spike protein immunoglobulin-G reactivity after booster vaccination than after the second vaccine dose suggest that the booster vaccine is not necessarily beneficial in young Bangladeshi adults having a history of repeated SARS-CoV-2 infections.

First hepatitis E outbreak in Southeastern Senegal.

The Rapid proliferation of traditional gold mining sites in the Kedougou region has led to massive migration of people from neighbouring West African countries and the establishment of several small villages where poor hygiene and sanitation conditions exist. In this context, a Hepatitis E virus outbreak was reported in Kedougou in 2014 with several cases among the traditional mining workers. Herein, we described epidemiological and laboratory data collected during the outbreak's investigation from February 2012 to November 2014. Any suspected, contact or probable case was investigated, clinical and epidemiological data were collected. In our study, sera were collected and tested for viral RNA and anti-Hepatitis E virus (HEV) IgM. Archived serum samples from Kedougou were retrospectively screened by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). A total of 65 water samples collected from ponds and wells surrounding gold panners' sites and habitats and 75 tissues samples from rats captured in the environment of traditional gold mining sites were also tested. A total of 1617 sera were collected from 698 suspected cases, 862 contacts and 57 persons with missing information. The median age was 20 (1-88 years-old) and the sex ratio was 1.72. An overall rate of 64.62% (1045/1617) of these patients tested positive for HEV with a high case fatality rate in pregnant women. All water samples and animal tissues tested negative for HEV. Our data help not only determining of the beginning of the HEV outbreak to March 2012, but also identifying risk factors associated to its emergence. However, there is a need to implement routine diagnosis, surveillance and training of health personnel in order to reduce mortality especially among pregnant women. In addition, further studies are needed to identify the virus reservoir and environmental risk factors for HEV in the Kedougou region.

Dual roles of mTORC1-dependent activation of the ubiquitin-proteasome system in muscle proteostasis.

Muscle size is controlled by the PI3K-PKB/Akt-mTORC1-FoxO pathway, which integrates signals from growth factors, energy and amino acids to activate protein synthesis and inhibit protein breakdown. While mTORC1 activity is necessary for PKB/Akt-induced muscle hypertrophy, its constant activation alone induces muscle atrophy. Here we show that this paradox is based on mTORC1 activity promoting protein breakdown through the ubiquitin-proteasome system (UPS) by simultaneously inducing ubiquitin E3 ligase expression via feedback inhibition of PKB/Akt and proteasome biogenesis via Nuclear Factor Erythroid 2-Like 1 (Nrf1). Muscle growth was restored by reactivation of PKB/Akt, but not by Nrf1 knockdown, implicating ubiquitination as the limiting step. However, both PKB/Akt activation and proteasome depletion by Nrf1 knockdown led to an immediate disruption of proteome integrity with rapid accumulation of damaged material. These data highlight the physiological importance of mTORC1-mediated PKB/Akt inhibition and point to juxtaposed roles of the UPS in atrophy and proteome integrity.

Molecular and Serological Characterization of the SARS-CoV-2 Delta Variant in Bangladesh in 2021.

Novel SARS-CoV-2 variants are emerging at an alarming rate. The delta variant and other variants of concern (VoC) carry spike (S)-protein mutations, which have the potential to evade protective immunity, to trigger break-through infections after COVID-19 vaccination, and to propagate future waves of COVID-19 pandemic. To identify SARS CoV-2 variants in Bangladesh, patients who are RT-PCR-positive for COVID-19 infections in Dhaka were screened by a RT-PCR melting curve analysis for spike protein mutations. To assess the anti-SARS CoV-2 antibody responses, the levels of the anti-S -proteins IgA and IgG and the anti-N-protein IgG were measured by ELISA. Of a total of 36 RT-PCR positive samples (75%), 27 were identified as delta variants, with one carrying an additional Q677H mutation and two with single nucleotide substitutions at position 23029 (compared to Wuhan-Hu-1 reference NC 045512) in the genome sequence. Three (8.3%) were identified as beta variants, two (5.5%) were identified as alpha variants, three (8.3%) were identified as having a B.1.1.318 lineage, and one sample was identified as an eta variant (B.1.525) carrying an additional V687L mutation. The trend of higher viral load (lower Cp values) among delta variants than in the alpha and beta variants was of borderline statistical significance (p = 0.045). Prospective studies with larger Bangladeshi cohorts are warranted to confirm the emergence of S-protein mutations and their association with antibody response in natural infection and potential breakthrough in vaccinated subjects.

The National Academies Report on Sexually Transmitted Infections: Implications for Clinical Training, Licensing, and Practice Guidelines.

Sexually transmitted infections (STIs) represent a sizable, longstanding, and growing challenge and a national public health priority. A recent National Academies report outlines new directions for STI prevention and control, including the adoption of a new sexual health paradigm and broader ownership and accountability for addressing sexual health and STIs among diverse clinical and nonclinical actors. These recommendations have important implications for infectious disease providers with STI and human immunodeficiency virus (HIV) expertise. As part of the envisioned shift toward greater prioritization of sexual health across systems for healthcare and health promotion, STI and HIV specialty providers will need to increasingly take on responsibilities as leaders in the provision of STI-related training; provision of technical assistance; and alignment of clinical training curricula, licensing criteria, and practice guidelines for healthcare generalists.

Nurses at the frontline of public health emergency preparedness and response: lessons learned from the HIV/AIDS pandemic and emerging infectious disease outbreaks.

The years 2020-21, designated by WHO as the International Year of the Nurse and Midwife, are characterised by unprecedented global efforts to contain and mitigate the COVID-19 pandemic. Lessons learned from successful pandemic response efforts in the past and present have implications for future efforts to leverage the global health-care workforce in response to outbreaks of emerging infectious diseases such as COVID-19. Given its scale, reach, and effectiveness, the response to the HIV/AIDS pandemic provides one such valuable example, particularly with respect to the pivotal, although largely overlooked, contributions of nurses and midwives. This Personal View argues that impressive achievements in the global fight against HIV/AIDS would not have been attained without the contributions of nurses. We discuss how these contributions uniquely position nurses to improve the scale, reach, and effectiveness of response efforts to emerging infectious diseases with pandemic potential; provide examples from the responses to COVID-19, Zika virus disease, and Ebola virus disease; and discuss implications for current and future efforts to strengthen pandemic preparedness and response.

Suitcase Lab for Rapid Detection of SARS-CoV-2 Based on Recombinase Polymerase Amplification Assay.

In March 2020, the SARS-CoV-2 virus outbreak was declared as a world pandemic by the World Health Organization (WHO). The only measures for controlling the outbreak are testing and isolation of infected cases. Molecular real-time polymerase chain reaction (PCR) assays are very sensitive but require highly equipped laboratories and well-trained personnel. In this study, a rapid point-of-need detection method was developed to detect the RNA-dependent RNA polymerase (RdRP), envelope protein (E), and nucleocapsid protein (N) genes of SARS-CoV-2 based on the reverse transcription recombinase polymerase amplification (RT-RPA) assay. RdRP, E, and N RT-RPA assays required approximately 15 min to amplify 2, 15, and 15 RNA molecules of molecular standard/reaction, respectively. RdRP and E RT-RPA assays detected SARS-CoV-1 and 2 genomic RNA, whereas the N RT-RPA assay identified only SARS-CoV-2 RNA. All established assays did not cross-react with nucleic acids of other respiratory pathogens. The RT-RPA assay's clinical sensitivity and specificity in comparison to real-time RT-PCR (n = 36) were 94 and 100% for RdRP; 65 and 77% for E; and 83 and 94% for the N RT-RPA assay. The assays were deployed to the field, where the RdRP RT-RPA assays confirmed to produce the most accurate results in three different laboratories in Africa (n = 89). The RPA assays were run in a mobile suitcase laboratory to facilitate the deployment at point of need. The assays can contribute to speed up the control measures as well as assist in the detection of COVID-19 cases in low-resource settings.

Reconsidering Assumptions of Adolescent and Young Adult Severe Acute Respiratory Syndrome Coronavirus 2 Transmission Dynamics.

Evidence regarding the important role of adolescents and young adults (AYA) in accelerating and sustaining coronavirus disease 2019 (COVID-19) outbreaks is growing. Furthermore, data suggest that 2 known factors that contribute to high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissibility-presymptomatic transmission and asymptomatic case presentations-may be amplified in AYA. However, AYA have not been prioritized as a key population in the public health response to the COVID-19 pandemic. Policy decisions that limit public health attention to AYA and are driven by the assumption of insignificant forward transmission from AYA pose a risk of inadvertent reinvigoration of local transmission dynamics. In this viewpoint, we highlight evidence regarding the increased potential of AYA to transmit SARS-CoV-2 that, to date, has received little attention, discuss adolescent and young adult-specific considerations for future COVID-19 control measures, and provide applied programmatic suggestions.

The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia.

With human median lifespan extending into the 80s in many developed countries, the societal burden of age-related muscle loss (sarcopenia) is increasing. mTORC1 promotes skeletal muscle hypertrophy, but also drives organismal aging. Here, we address the question of whether mTORC1 activation or suppression is beneficial for skeletal muscle aging. We demonstrate that chronic mTORC1 inhibition with rapamycin is overwhelmingly, but not entirely, positive for aging mouse skeletal muscle, while genetic, muscle fiber-specific activation of mTORC1 is sufficient to induce molecular signatures of sarcopenia. Through integration of comprehensive physiological and extensive gene expression profiling in young and old mice, and following genetic activation or pharmacological inhibition of mTORC1, we establish the phenotypically-backed, mTORC1-focused, multi-muscle gene expression atlas, SarcoAtlas (https://sarcoatlas.scicore.unibas.ch/), as a user-friendly gene discovery tool. We uncover inter-muscle divergence in the primary drivers of sarcopenia and identify the neuromuscular junction as a focal point of mTORC1-driven muscle aging.