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Abstract Spinal cord injury creates an inflammatory microenvironment that regulates the capacity of transplanted human Neural Stem Cells (hNSC) to migrate, differentiate, and repair injury. Despite similarities in gene expression and markers detected by immunostaining, hNSC populations exhibit heterogeneous therapeutic potential. This heterogeneity derives in part from the epigenetic landscape in the hNSC genome, specifically methylation (5mC) and hydroxymethylation (5hmC) state, which may affect the response of transplanted hNSC in the injury microenvironment and thereby modulate repair capacity. We demonstrate a significant up-regulation of methylcytosine dioxygenase 2 gene (TET2) expression in undifferentiated hNSC derived from human embryonic stem cells (hES-NSC), and report that this is associated with hES-NSC competence for differentiation marker expression. TET2 protein catalyzes active demethylation and TET2 upregulation could be a signature of pluripotent exit, while shaping the epigenetic landscape in hES-NSC. We determine that the inflammatory environment overrides epigenetic programming in vitro and in vivo by directly modulating TET2 expression levels in hES-NSC to change cell fate. We also report the effect of cell fate and microenvironment on differential methylation 5mC/5hmC balance. Understanding how the activity of epigenetic modifiers changes within the transplantation niche in vivo is crucial for assessment of hES-NSC behavior for potential clinical applications.

Abstract Docetaxel is commonly used for treatment of castration-resistant prostate cancer. Unfortunately, many prostate cancer patients develop resistance to docetaxel. Clinical markers less invasive than biopsies, such as blood samples, would be ideal for monitoring and predicting patient treatment outcomes to docetaxel. Lipid alterations are often associated with the progression of many cancers, including prostate cancer. This study investigated the use of lipids from whole blood as clinical markers for docetaxel resistance in a small cohort of patients with prostate cancer. Qualitative lipidomics was performed by liquid chromatography-tandem mass spectrometry to assess the lipid composition of prostate cancer cells exposed to docetaxel as well as whole blood from prostate cancer patients before, during and after docetaxel treatment. Three patients had castration resistant prostate cancer, three had castration sensitive prostate cancer, and four had de novo prostate cancer during the extent of the study. Mean decrease accuracy and classical univariate receiving operating characteristic curve analyses were performed to identify potential biomarkers. In total, 245 and 221 altered lipids were identified from a second stage of mass spectrometry analysis of prostate cancer cells and clinical blood samples, respectively. Both models indicated that docetaxel treatment altered ether-linked phosphatidylcholines, lysophosphatidylcholine, diacylglycerols, ceramides, hexosylceramides, and sphingomyelins. The results also indicated several lipid changes were associated with sphingolipid signaling and metabolism, and glycerophospholipid metabolism. Collectively, these data suggest the potential usage of identified lipid species as indicators of docetaxel resistance in prostate cancer.

Objective: This study estimated prevalence of current electronic nicotine delivery systems (ENDS) used by US adults who smoked cigarettes or formerly smoked in 2022 and assessed ENDS flavors, devices, and brands used most often. Methods: Data are from the 2022 US ITC Smoking and Vaping Survey. Respondents were recruited from a web panel of a nationally representative sample of US adults ages 18+ who smoked, formerly smoked, and/or vaped ENDS. Using weighted data, we estimated prevalence of current vaping among adults who smoke or formerly smoked (N = 2,016). Among the subset who vaped (n = 554), we assessed flavors and devices used most often. Using unweighted data, we assessed the frequency (count) of reported brands used most often. Results: In 2022, 22.0 % of US adults who smoked or formerly smoked were vaping at least monthly. A significantly higher proportion of adults who formerly smoked and/or were younger (18–39) were vaping than adults who were smoking and/or were older (40+) (both p

Abstract Background/Objectives Transitions to and from Emergency Departments (EDs) can be detrimental to long‐term care (LTC) residents and burden the healthcare system. While reducing avoidable transfers is imperative, various terms are used interchangeably including inappropriate, preventable, or unnecessary transitions. Our study objectives were to develop a conceptual definition of avoidable LTC‐ED transitions and to verify the level of stakeholder agreement with this definition. Methods The EXamining Aged Care Transitions study adopted an exploratory sequential mixed‐method design. The study was conducted in 2015–2016 in 16 LTC facilities, 1 ED, and 1 Emergency Medical Service (EMS) in a major urban center in western Canada. Phase 1 included 80 participants, (healthcare aides, licensed practical nurses, registered nurses, LTC managers, family members of residents, and EMS staff). We conducted semistructured interviews (n = 25) and focus groups (n = 19). In Phase 2, 327 ED staff, EMS staff, LTC staff, and medical directors responded to a survey based on the qualitative findings. Results Avoidable transitions were attributed to limited resources in LTC, insufficient preventive care, and resident or family wishes. The definition generated was: A transition of an LTC resident to the ED is considered avoidable if: (a) Diagnostic testing, medical assessment, and treatment can be accessed in a timely manner by other means; (b) the reasons for a transfer are unclear and the transition would increase the disorientation, pain, or discomfort of a resident, outweighing a clear benefit of a transfer; and (c) the transition is against the wishes expressed by the resident over time, including through informal and undocumented conversations. There was a high level of agreement with the definition across the four participant groups. Conclusions and Implications To effectively reduce LTC resident avoidable transitions, stakeholders must share a common definition. Our conceptual definition may significantly contribute to improved care for LTC residents.

Abstract VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20–150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood–brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p

Abstract Regeneration in the injured spinal cord is limited by physical and chemical barriers. Acute implantation of a multichannel poly(lactide-co-glycolide) (PLG) bridge mechanically stabilizes the injury, modulates inflammation, and provides a permissive environment for rapid cellularization and robust axonal regrowth through this otherwise inhibitory milieu. However, without additional intervention, regenerated axons remain largely unmyelinated (

Objective We investigated whether a zip code’s location or demographics are most predictive of changes in daily mobility throughout the course of the COVID-19 pandemic.Design We used a population-level study to examine the predictability of daily mobility during the COVID-19 pandemic using a two-stage regression approach, where generalised additive models (GAM) predicted mobility trends over time at a large spatial level, then the residuals were used to determine which factors (location, zip code-level features or number of non-pharmaceutical interventions (NPIs) in place) best predict the difference between a zip code’s measured mobility and the average trend on a given date.Setting We analyse zip code-level mobile phone records from 26 metropolitan areas in the USA on 15 March–31 September 2020, relative to October 2020.Results While relative mobility had a general trend, a zip code’s city-level location significantly helped to predict its daily mobility patterns. This effect was time-dependent, with a city’s deviation from general mobility trends differing in both direction and magnitude throughout the course of 2020. The characteristics of a zip code further increased predictive power, with the densest zip codes closest to a city centre tended to have the largest decrease in mobility. However, the effect on mobility change varied by city and became less important over the course of the pandemic.Conclusions The location and characteristics of a zip code are important for determining changes in daily mobility patterns throughout the course of the COVID-19 pandemic. These results can determine the efficacy of NPI implementation on multiple spatial scales and inform policy makers on whether certain NPIs should be implemented or lifted during the ongoing COVID-19 pandemic and when preparing for future public health emergencies.

Introduction Decisions about nurse staffing models are a concern for health systems globally due to workforce retention and well-being challenges. Nurse staffing models range from all Registered Nurse workforce to a mix of differentially educated nurses and aides (regulated and unregulated), such as Licensed Practical or Vocational Nurses and Health Care Aides. Systematic reviews have examined relationships between specific nurse staffing models and client, staff and health system outcomes (eg, mortality, adverse events, retention, healthcare costs), with inconclusive or contradictory results. No evidence has been synthesised and consolidated on how, why and under what contexts certain staffing models produce different outcomes. We aim to describe how we will (1) conduct a realist review to determine how nurse staffing models produce different client, staff and health system outcomes, in which contexts and through what mechanisms and (2) coproduce recommendations with decision-makers to guide future research and implementation of nurse staffing models.Methods and analysis Using an integrated knowledge translation approach with researchers and decision-makers as partners, we are conducting a three-phase realist review. In this protocol, we report on the final two phases of this realist review. We will use Citation tracking, tracing Lead authors, identifying Unpublished materials, Google Scholar searching, Theory tracking, ancestry searching for Early examples, and follow-up of Related projects (CLUSTER) searching, specifically designed for realist searches as the review progresses. We will search empirical evidence to test identified programme theories and engage stakeholders to contextualise findings, finalise programme theories document our search processes as per established realist review methods.Ethics and dissemination Ethical approval for this study was provided by the Health Research Ethics Board of the University of Alberta (Study ID Pro00100425). We will disseminate the findings through peer-reviewed publications, national and international conference presentations, regional briefing sessions, webinars and lay summary.

Abstract Background Pain is highly burdensome, affecting over 30% of long-term care (LTC) residents. Pain significantly reduces residents’ health-related quality of life (HRQoL), limits their ability to perform activities of daily living (ADLs), restricts their social activities, and can lead to hopelessness, depression, and unnecessary healthcare costs. Although pain can generally be prevented or treated, eliminating pain may not always be possible, especially when residents have multiple chronic conditions. Therefore, improving the HRQoL of LTC residents with pain is a priority goal. Understanding factors influencing HRQoL of LTC residents with pain is imperative to designing and evaluating targeted interventions that complement pain management to improve residents’ HRQoL. However, these factors are poorly understood, and we lack syntheses of available research on this topic. This systematic review protocol outlines the methods to identify, synthesize, and evaluate the available evidence on these factors. Methods This mixed methods review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We will systematically search Medline, EMBASE, PsycINFO, CINAHL, Scopus, Cochrane Database of Systematic Reviews and ProQuest Dissertation and Thesis Global from database inception. We will include primary studies and systematically conducted reviews without restrictions to language, publication date, and study design. We will also include gray literature (dissertation and reports) and search relevant reviews and reference lists of all included studies. Two reviewers will independently screen articles, conduct quality appraisal, and extract data. We will synthesize results thematically and conduct meta-analyses if statistical pooling is possible. Residents and family/friend caregivers will assist with interpreting the findings. Discussion This proposed systematic review will address an important knowledge gap related to the available evidence on factors influencing HRQoL of LTC residents with pain. Findings will be crucial for researchers, LTC administrators, and policy makers in uncovering research needs and in planning, developing, and evaluating strategies in addition to and complementary with pain management to help improve HRQoL among LTC residents with pain. Systematic review registration PROSPERO CRD42023405425

Introduction Young people aged 18–24 years old are a key demographic target for eliminating HIV transmission globally. Pre-exposure prophylaxis (PrEP), a prevention medication, reduces HIV transmission. Despite good uptake by gay and bisexual men who have sex with men, hesitancy to use PrEP has been observed in other groups, such as young people and people from ethnic minority backgrounds. The aim of this study was to explore young people’s perceptions and attitudes to using PrEP.Design A qualitative transcendental phenomenological design was used.Participants and setting A convenience sample of 24 young people aged between 18 and 24 years was recruited from England.Methods Semistructured interviews and graphical elicitation were used to collect data including questions about current experiences of HIV care, awareness of using PrEP and decision-making about accessing PrEP. Thematic and visual analyses were used to identify findings.Results Young people had good levels of knowledge about HIV but poor understanding of using PrEP. In this information vacuum, negative stigma and stereotypes about HIV and homosexuality were transferred to using PrEP, which were reinforced by cultural norms portrayed on social media, television and film—such as an association between using PrEP and being a promiscuous, white, gay male. In addition, young people from ethnic minority communities appeared to have negative attitudes to PrEP use, compared with ethnic majority counterparts. This meant these young people in our study were unable to make decisions about when and how to use PrEP.Conclusion Findings indicate an information vacuum for young people regarding PrEP. A strength of the study is that theoretical data saturation was reached. A limitation of the study is participants were largely from Northern England, which has low prevalence of HIV. Further work is required to explore the information needs of young people in relation to PrEP.

Abstract Solar geoengineering is a controversial climate policy measure that could lower global temperature by increasing the amount of light reflected by the Earth. As scientists and policymakers increasingly consider this idea, an understanding of the level and drivers of public support for its research and potential deployment will be key. This study focuses on the role of climate change information in public support for research and deployment of stratospheric aerosol injection (SAI) in Singapore (n = 503) and the United States (n = 505). Findings were consistent with the idea that exposure to information underlies support for research and deployment. That finding was stronger in the United States, where climate change is a more contentious issue, than in Singapore. Cost concern was negatively related to support for funding and perceived risk was negatively related to support for deployment. Perceived government efficacy was a more positive predictor of support for funding in Singapore than in the United States. Additionally, relatively low support for local deployment was consistent with a NIMBY mindset. This was the first study to quantify the role of climate change information in SAI policy support, which has practical implications for using the media and interpersonal channels to communicate about SAI policy measures.

Abstract Background Emotional support is key to improve older adults’ subjective health, and psychological, social and emotional well-being. However, many older adults living in the community lack emotional support, increasing the risk for loneliness, depression, anxiety, potentially avoidable healthcare use and costs, and premature death. Multiple intersecting factors may influence emotional support of older adults in the community, but these are poorly understood. Studies have focused on specific populations (e.g., older adults with depression, cancer). Although relevant, these studies may not capture modifiable factors for the wider and more diverse population of older adults living in the community. Our scoping review will address these important gaps. We will identify and synthesize the evidence on factors that influence emotional support of older adults in the community. Methods We will use the Johanna Briggs Institute updated methodological guidance for the conduct of scoping reviews to guide our review process. We will search MEDLINE, EMBASE, APA Psycinfo, CINAHL, Dissertations and Theses Global, and Scopus from inception. We will include studies published in English, examining factors influencing emotional support of older adults residing in community, without restrictions on the study design or year of publication. We will also include gray literature (dissertations and reports). Two independent reviewers will conduct title, abstract, and full-text screening, as well as risk of bias assessment, using validated quality appraisal tools based on study designs. Discrepancies will be resolved by consensus. The primary reviewer will extract the data from all studies, and the second reviewer will check the extractions of all the studies. We will use descriptive statistics and narrative synthesis for analysis. Family/friend caregivers and older adults involved as an advisory group will help with explaining the findings in terms of whether associations observed reflect their experiences and reality. We will analyze the discussion and generate themes, and summarize in a narrative form. Discussion This scoping review may identify factors that could be modified or mitigated to improve emotional support provision for older adults residing in community. The knowledge will inform the development of tailored interventions directed to older adults and their caregivers. Systematic review registration https://doi.org/10.17605/OSF.IO/4TAEB (associated project link: osf.io/6y48t).

A Vibrio cholerae O1 outbreak emerged in Haiti in October 2022 after years of cholera absence. In samples from a 2021 serosurvey, we found lower circulating antibodies against V. cholerae lipopolysaccharide in children

Abstract A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer’s disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual’s risk for the disease. Using the largest genome-wide association study of gut microbiota genera from the MiBioGen consortium, we used polygenic risk score (PRS) analyses with the “best-fit” model implemented in PRSice-2 and determined the genetic correlation between 119 genera and AD in a discovery sample (ADc12 case/control: 1278/1293). To confirm the results from the discovery sample, we next repeated the PRS analysis in a replication sample (GenADA case/control: 799/778) and then performed a meta-analysis with the PRS results from both samples. Finally, we conducted a linear regression analysis to assess the correlation between the PRSs for the significant genera and the APOE genotypes. In the discovery sample, 20 gut microbiota genera were initially identified as genetically associated with AD case/control status. Of these 20, three genera (Eubacterium fissicatena as a protective factor, Collinsella, and Veillonella as a risk factor) were independently significant in the replication sample. Meta-analysis with discovery and replication samples confirmed that ten genera had a significant correlation with AD, four of which were significantly associated with the APOE rs429358 risk allele in a direction consistent with their protective/risk designation in AD association. Notably, the proinflammatory genus Collinsella, identified as a risk factor for AD, was positively correlated with the APOE rs429358 risk allele in both samples. Overall, the host genetic factors influencing the abundance of ten genera are significantly associated with AD, suggesting that these genera may serve as biomarkers and targets for AD treatment and intervention. Our results highlight that proinflammatory gut microbiota might promote AD development through interaction with APOE. Larger datasets and functional studies are required to understand their causal relationships.

In post-industrial settings, apolipoprotein E4 (APOE4) is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N = 1266, 50% female), APOE4 is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized LDL and inflammation which were limited to obese adults. Further, APOE4 carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between APOE4 and lipids may be beneficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.

IntroductionBurnout poses a substantial, ongoing threat to healthcare worker (HCW) wellbeing and to the delivery of safe, quality healthcare. While systemic and organization-level changes in healthcare are critically important, HCWs also need individual-level skills to promote resilience. The objective of this trial is to test feasibility, acceptability, and efficacy of PARK, an online self-guided positive affect regulation intervention, in a sample of healthcare workers during the COVID-19 pandemic.Design and methodsIn the context of the unprecedented rise in burnout during the COVID-19 pandemic, we conducted a randomized waitlist-controlled trial of the Positive Affect Regulation sKills (PARK) program-a five-week, online, self-guided coping skills intervention nested within an ongoing cohort of HCWs. N = 554 healthcare workers were randomly assigned to receive the intervention immediately or to receive the intervention after approximately 12 weeks. Outcomes included change in burnout, emotional wellbeing (positive affect, meaning and purpose, depression, anxiety) and sleep over approximately 12 weeks. Analyses included mixed-effects linear regression models comparing change over time in outcomes between intervention and control conditions.ResultsOne third (n = 554) of the participants in the cohort of HCWs consented to participate and enrolled in PARK in April 2022. Compared to those who did not enroll, participants in the trial reported higher burnout, poorer emotional wellbeing, and poorer sleep at baseline (April, 2022; all ps < .05). Intent-to-treat analyses showed that participants randomly assigned to the intervention immediately (PARK-Now) improved significantly on anxiety (within-group change on PROMIS T-score = -0.63; p = .003) whereas those in the waitlist (PARK-Later) did not (within group T-score change 0.04, p = 0.90). The between-group difference in change, however, was not statistically significant (B = -0.67 p = 0.10). None of the other wellbeing outcomes changed significantly in the intervention group compared to the waitlist. Additional as-treated analyses indicated that those participants who completed all 5 of the weekly online lessons (N = 52; 9.4%) improved significantly more on the primary outcome of positive affect compared to those who enrolled in PARK but completed zero lessons (n = 237; 42.8%; B = 2.85; p = .0001).ConclusionsOnline self-guided coping skills interventions like PARK can be effective in targeted samples and future work will focus on adaptations to increase engagement and tailor PARK for HCWs who could most benefit.

[This corrects the article DOI: 10.1371/journal.pone.0200908.].

Epidemic data are often difficult to interpret due to inconsistent detection and reporting. As these data are critically relied upon to inform policy and epidemic projections, understanding reporting trends is similarly important. Early reporting of the COVID-19 pandemic in particular is complicated, due to changing diagnostic and testing protocols. An internal audit by the State of Florida, USA found numerous specific examples of irregularities in COVID-19 case and death reports. Using case, hospitalization, and death data from the the first year of the COVID-19 pandemic in Florida, we present approaches that can be used to identify the timing, direction, and magnitude of some reporting changes. Specifically, by establishing a baseline of detection probabilities from the first (spring) wave, we show that transmission trends among all age groups were similar, with the exception of the second summer wave, when younger people became infected earlier than seniors, by approximately 2 weeks. We also found a substantial drop in case-fatality risk (CFR) among all age groups over the three waves during the first year of the pandemic, with the most drastic changes seen in the 0 to 39 age group. The CFR trends provide useful insights into infection detection that would not be possible by relying on the number of tests alone. During the third wave, for which we have reliable hospitalization data, the CFR was remarkably stable across all age groups. In contrast, the hospitalization-to-case ratio varied inversely with cases while the death-to-hospitalization ratio varied proportionally. Although specific trends are likely to vary between locales, the approaches we present here offer a generic way to understand the substantial changes that occurred in the relationships among the key epidemic indicators.

BackgroundDiabetes distress among adolescents with type 1 diabetes has been associated with suboptimal diabetes outcomes, including lower quality of life, increased diabetes self-management challenges, and suboptimal glycemic outcomes. ObjectiveThis study examined the feasibility and acceptability of a scalable self-led mindfulness-based intervention to reduce diabetes distress in adolescents with type 1 diabetes. MethodsAdolescents (N=25) aged between 14 and 18 years diagnosed with type 1 diabetes completed a baseline assessment. Participants were randomized to receive a 10-week self-guided mindfulness-based stress reduction workbook program (e-book or paper option) immediately (n=15) or after a 10-week wait (n=10). During the intervention period, participants completed weekly assignments and feedback surveys. At 10 weeks and 20 weeks, follow-up assessments were completed. ResultsFindings indicated that participants did not find the original intervention feasible or acceptable. Adolescents reported barriers to completing the weekly material, such as that they forgot or that the material was not sufficiently related to their diabetes management. Adolescents also reported that a digital format rather than a workbook or e-book may be more acceptable. Results from weekly surveys provided the foundation for recommendations for future iterations of the mindfulness-based intervention for adolescents with type 1 diabetes. ConclusionsParticipant feedback informed recommendations for self-led mindfulness programs for youth with type 1 diabetes. Adolescents indicated that a shorter, digital mindfulness-based intervention focused on diabetes-specific behaviors may be more helpful. Trial RegistrationClinicalTrials.gov NCT05115175; https://clinicaltrials.gov/study/NCT05115175

This study examined associations between established cigar use and prevalence and incidence of cardiovascular diseases (CVD; congestive heart failure, stroke, or heart attack/needed bypass surgery) among U.S. adults, 40 years or older. Using Waves 1–5 (2013–2019) of the Population Assessment of Tobacco and Health (PATH) Study, incidence (Nindividuals (Nind) = 6,692; Nobservations (Nobs) = 23,738) and prevalence (Nind = 7,819; Nobs = 33,952) of CVD outcomes were examined using weighted generalized estimating equations (WGEEs) among adults who were exclusive current/former established cigar smokers (ever cigar smokers who have smoked fairly regularly), exclusive current/former established cigarette smokers (lifetime smokers of 100 or more cigarettes), dual current/former established cigarette and cigar smokers compared with never smokers of cigars or cigarettes, adjusting for covariates. The population-averaged incidence of CVD from one wave to next among exclusive current/former established cigar smokers during a six-year period based on WGEEs was low (overall average rate of 3.0 %; 95 % CI: 1.2, 7.0). Compared with never users, exclusive current/former established cigar smokers (OR = 1.67, 95 % CI: 1.11, 2.51) and exclusive current/former established cigarette smokers (OR = 2.12, 95 % CI: 1.45, 3.09) were more likely to have any CVD outcome in unadjusted analyses. When adjusted for covariates, only exclusive current/former established cigarette use was associated with CVD outcomes (AOR = 1.60, CI: 1.07, 2.40). Results suggest that exclusive established use of cigars or duration of exclusive cigar use was not associated with lifetime CVD prevalence compared with never cigar or cigarette smokers, which is important in understanding health outcomes in cigar users.

Objectives During the COVID-19 pandemic, most essential services experienced some level of disruption. Disruption in LMICs was more severe than in HICs. Early reports suggested that services for maternal and newborn health were disproportionately affected, raising concerns about health equity. Most disruption indicators measure demand-side disruption, or they conflate demand-side and supply-side disruption. There is currently no published guidance on measuring supply-side disruption. The primary objective of this review was to identify methods and approaches used to measure supply-side service disruptions to maternal and newborn health services in the context of COVID-19.Design We carried out a systematic review and have created a typology of measurement methods and approaches using narrative synthesis.Data sources We searched MEDLINE, EMBASE and Global Health in January 2023. We also searched the grey literature.Eligibility criteria We included empirical studies describing the measurement of supply-side service disruption of maternal and newborn health services in LMICs in the context of COVID-19.Data extraction and synthesis We extracted the aim, method(s), setting, and study outcome(s) from included studies. We synthesised findings by type of measure (ie, provision or quality of services) and methodological approach (ie, qualitative or quantitative).Results We identified 28 studies describing 5 approaches to measuring supply-side disruption: (1) cross-sectional surveys of the nature and experience of supply-side disruption, (2) surveys to measure temporal changes in service provision or quality, (3) surveys to create composite disruption scores, (4) surveys of service users to measure receipt of services, and (5) clinical observation of the provision and quality of services.Conclusion Our review identified methods and approaches for measuring supply-side service disruption of maternal and newborn health services. These indicators provide important information about the causes and extent of supply-side disruption and provide a useful starting point for developing specific guidance on the measurement of service disruption in LMICs.

Abstract Background Since the beginning of the COVID-19 pandemic, several variants of concern (VOC) have emerged for which there is evidence of an increase in transmissibility, more severe disease, and/or reduced vaccine effectiveness. Effective COVID-19 vaccine strategies are required to achieve broad protective immunity against current and future VOC. Methods We conducted immunogenicity and challenge studies in macaques and hamsters using a bivalent recombinant vaccine formulation containing the SARS-CoV-2 prefusion-stabilized Spike trimers of the ancestral D614 and the variant Beta strains with AS03 adjuvant (CoV2 preS dTM-AS03) in a primary immunization setting. Results We show that a primary immunization with the bivalent CoV2 preS dTM-AS03 elicits broader and durable (1 year) neutralizing antibody responses against VOC including Omicron BA.1 and BA.4/5, and SARS-CoV-1 as compared to the ancestral D614 or Beta variant monovalent vaccines in naïve non-human primates. In addition, the bivalent formulation confers protection against viral challenge with SARS-CoV-2 prototype D614G strain as well as Alpha and Beta variant strains in hamsters. Conclusions Our findings demonstrate the potential of a Beta-containing bivalent CoV2 preS dTM-AS03 formulation to provide broad and durable immunogenicity, as well as protection against VOC in naïve populations.

Abstract Older adults with type 1 diabetes (T1D) have unique challenges and needs. In this mixed-methods study, we explored the impact of isolation during a pandemic on diabetes management and overall quality of life in this population. Older adults (age ≥ 65 years) with T1D receiving care at a tertiary care diabetes center participated in semi-structured interviews during COVID-19 pandemic isolation between June and August 2020. A multi-disciplinary team coded transcripts and conducted thematic analysis. Thirty-four older adults (age 71 ± 5 years, 97% non-Hispanic white, diabetes duration of 38 ± 7 years, A1C of 7.4 ± 0.9% (57.3 ± 10.1 mmol/mol) were recruited. Three themes related to diabetes self-care emerged regarding impact of isolation on: (1) diabetes management and self-care behaviors (how isolation prompted changes in physical activity and dietary habits); (2) emotional stress and anxiety (related to isolation and lack of support system, economic concerns); and (3) concerns regarding the COVID-19 pandemic (impact on timely medical care and access to information). Our findings identify modifiable barriers and challenges faced by older adults with T1D during isolation. As this population has a higher risk of decline in physical and psychosocial support even during non-pandemic times, clinicians will benefit from understanding these issues to improve care of this population.

Abstract Microbial glycan microarrays (MGMs) populated with purified microbial glycans have been used to define the specificity of host immune factors toward microbes in a high throughput manner. However, a limitation of such arrays is that glycan presentation may not fully recapitulate the natural presentation that exists on microbes. This raises the possibility that interactions observed on the array, while often helpful in predicting actual interactions with intact microbes, may not always accurately ascertain the overall affinity of a host immune factor for a given microbe. Using galectin-8 (Gal-8) as a probe, we compared the specificity and overall affinity observed using a MGM populated with glycans harvested from various strains of Streptococcus pneumoniae to an intact microbe microarray (MMA). Our results demonstrate that while similarities in binding specificity between the MGM and MMA are apparent, Gal-8 binding toward the MMA more accurately predicted interactions with strains of S. pneumoniae, including the overall specificity of Gal-8 antimicrobial activity. Taken together, these results not only demonstrate that Gal-8 possesses antimicrobial activity against distinct strains of S. pneumoniae that utilize molecular mimicry, but that microarray platforms populated with intact microbes present an advantageous strategy when exploring host interactions with microbes.

Abstract The aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors.

Abstract Systemic sclerosis (SSc)-related digital ischaemia is a major cause of morbidity, resulting from a combination of microvascular and digital artery disease. Photoacoustic imaging offers a newly available, non-invasive method of imaging digital artery structure and oxygenation. The aim of this study was to establish whether photoacoustic imaging could detect and measure vasculopathy in digital arteries, including the level of oxygenation, in patients with SSc and healthy controls. 22 patients with SSc and 32 healthy controls (HC) underwent photoacoustic imaging of the fingers. Vascular volume and oxygenation were assessed across eight fingers at the middle phalanx. In addition, oxygenation change during finger occlusion was measured at the non-dominant ring finger and the vascular network was imaged along the length of one finger for qualitative assessment. There was no statistically significant difference in vascular volume between patients with SSc and HC (mean of eight fingers; SSc, median 118.6 IQR [95.0–130.5] vs. HC 115.6 [97.8–158.9]) mm3. However, baseline oxygenation (mean 8 fingers) was lower in SSc vs. HC (0.373 [0.361–0.381] vs. 0.381 [0.373–0.385] arbitrary sO2 units respectively; p = 0.03). Hyperaemic oxygenation response following occlusion release was significantly lower in SSc compared to HC (0.379 [0.376–0.381] vs. 0.382 [0.377–0.385]; p = 0.03). Whilst vascular volume was similar between groups, digital artery oxygenation was decreased in patients with SSc as compared to HC, indicative of functional deficit. Photoacoustic imaging offers an exciting new method to image the vascular network in patients with SSc and the possibility to capture oxygenation as a functional measure.

Summary: Background: Anti-amyloid vaccines may offer a convenient, affordable, and accessible means of preventing and treating Alzheimer's disease. UB-311 is an anti–amyloid-β active immunotherapeutic vaccine shown to be well-tolerated and to have a durable antibody response in a phase 1 trial. This phase 2a study assessed the safety, immunogenicity, and preliminary efficacy of UB-311 in participants with mild Alzheimer's disease. Methods: A 78-week, randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 2a study was conducted in Taiwan. Participants were randomised in a 1:1:1 ratio to receive seven intramuscular injections of UB-311 (Q3M arm), or five doses of U311 with two doses of placebo (Q6M arm), or seven doses of placebo (placebo arm). The primary endpoints were safety, tolerability, and immunogenicity of UB-311. Safety was assessed in all participants who received at least one dose of investigational product. This study was registered at ClinicalTrials.gov (NCT02551809). Findings: Between 7 December 2015 and 28 August 2018, 43 participants were randomised. UB-311 was safe, well-tolerated, and generated a robust immune response. The three treatment-emergent adverse events (TEAEs) with the highest incidence were injection-site pain (14 TEAEs in seven [16%] participants), amyloid-related imaging abnormality with microhaemorrhages and haemosiderin deposits (12 TEAEs in six [14%] participants), and diarrhoea (five TEAEs in five [12%] participants). A 97% antibody response rate was observed and maintained at 93% by the end of the study across both UB-311 arms. Interpretation: These results support the continued development of UB-311. Funding: Vaxxinity, Inc. (Formerly United Neuroscience Ltd.)

Several nicotine vaping product (NVP) device types are available to consumers, and many people who smoke report vaping to help them quit. This study included data from the Wave 3 (2020) ITC Smoking and Vaping Survey in the US, Canada, and England and included 2324 adults who were smoking cigarettes and vaping at least weekly. Device types currently used most often (disposables, cartridges/pods, or tank systems) were assessed using weighted descriptive statistics. Multivariable regression analyses were used to compare differences between respondents who reported vaping to quit smoking (‘yes’ vs. ‘no/don’t know’) by device type, overall and by country. Overall, 71.3% of respondents reported vaping to help them quit smoking, with no country differences (p = 0.12). Those using tanks (78.7%, p

Glaser et al. develop a deep learning system to predict all-cause mortality from total-body DXA scans. Their best predictive model integrates longitudinal body composition data with traditional mortality risk factors.

Abstract Digital health can reduce CO2 emissions thanks to telemedicine and access to digital test results and medical reports. However, the environmental impact of digital health activity is not well known. Here, we show that telemedicine reduces CO2 emissions. We found a net total of 6,655 tons of CO2 emissions decrease through a reduction in patient travel to surgeries and medical clinics thanks to the alternatives of digital appointments and digital access to test results and medical reports, which avoid the need to travel to a clinic for a face-to-face visit or to pick up printed results or reports. During 2020, a total of 640,122 digital appointments were carried out by the health care company, which avoided 1,957 net tons of CO2 emissions, while patients downloaded 3,064,646 digital medical reports through the company portal, which avoided an additional 4,698 net tons of CO2 emissions. Our results demonstrate how digital appointments and digital reports, reduce CO2 emissions by reducing the need for patient travel.

Abstract The Madin-Darby canine kidney (MDCK) cell line is an in vitro model for influenza A virus (IAV) infection and propagation. MDCK-SIAT1 (SIAT1) and humanized MDCK (hCK) cell lines are engineered MDCK cells that express N-glycans with elevated levels of sialic acid (Sia) in α2,6-linkage (α2,6-Sia) that are recognized by many human IAVs. To characterize the N-glycan structures in these cells and the potential changes compared to the parental MDCK cell line resulting from engineering, we analyzed the N-glycans from these cells at different passages, using both mass spectrometry and specific lectin and antibody binding. We observed significant differences between the three cell lines in overall complex N-glycans and terminal galactose modifications. MDCK cells express core fucosylated, bisected complex-type N-glycans at all passage stages, in addition to expressing α2,6-Sia on short N-glycans and α2,3-Sia on larger N-glycans. By contrast, SIAT1 cells predominantly express α2,6-Sia glycans and greatly reduced level of α2,3-Sia glycans. Additionally, they express bisected, sialylated N-glycans that are scant in MDCK cells. The hCK cells exclusively express α2,6-Sia glycans. Unexpectedly, hCK glycoproteins bound robustly to the plant lectin MAL-1, indicating α2,3-Sia glycans, but such binding was not Sia-dependent and closely mirrored that of an antibody that recognizes glycans with terminal 3-O-sulfate galactose (3-O-SGal). The 3-O-SGal epitope is highly expressed in N-glycans on multiple hCK glycoproteins. These results indicate vastly different N-glycomes between MDCK cells and the engineered clones that could relate to IAV infectivity.

Abstract Studies of microbiota reveal inter-relationships between the microbiomes of the gut and lungs. This relationship may influence the progression of lung disease, particularly in patients with cystic fibrosis (CF), who often experience extraoesophageal reflux (EOR). Despite identifying this relationship, it is not well characterised. Our hypothesis is that the gastric and lung microbiomes in CF are related, with the potential for aerodigestive pathophysiology. We evaluated gastric and sputum bacterial communities by culture and 16S rRNA gene sequencing in 13 CF patients. Impacts of varying levels of bile acids, pepsin and pH on patient isolates of Pseudomonas aeruginosa (Pa) were evaluated. Clonally related strains of Pa and NTM were identified in gastric and sputum samples from patients with symptoms of EOR. Bacterial diversity was more pronounced in sputa compared to gastric juice. Gastric and lung bile and pepsin levels were associated with Pa biofilm formation. Analysis of the aerodigestive microbiomes of CF patients with negative sputa indicates that the gut can be a reservoir of Pa and NTM. This combined with the CF patient’s symptoms of reflux and potential aspiration, highlights the possibility of communication between microorganisms of the gut and the lungs. This phenomenon merits further research.

Aim: Short-acting β2-agonist (SABA) overuse adversely impacts asthma-related outcomes and the environment. The SABA rEductioN Through ImplemeNting Hull asthma guidELines (SENTINEL) programme aims to reduce SABA overuse through supported implementation of an adult asthma guideline, which advocates for a SABA-free maintenance and reliever therapy (MART)-preferred treatment where appropriate, across six primary care networks (PCNs) in the UK. We present findings on patient/disease characteristics, asthma prescribing patterns and exacerbation rates from the pilot PCN. Methods: Patients (aged ≥18 years, prescribed at least one inhaled therapy) and their prescribed asthma treatments were characterised using National Health Service data. Asthma treatments and exacerbations were analysed for three periods: 24‒12 months pre-, 12 months pre- and 12 months post-SENTINEL implementation (November 2020‒January 2021). Results: Of the 2571 registered asthma patients, 33.6% (n=864) underwent an asthma review, of whom 44.7% (n=386) were transitioned to MART. Fewer patients were prescribed three or more SABA canisters per year post-implementation in the overall asthma population (45.4% and 46.2% during 24‒12 months and 12 months pre-implementation, respectively, and 23.9% 12 months post-implementation), and in the two subgroups: 1) those who had an asthma review (74.5% and 83.6% during 24‒12 months and 12 months pre-implementation, respectively, and 26.5% post-implementation); and 2) those transitioned to MART following a review (76.4% and 86.5% during 24‒12 months and 12 months pre-implementation, respectively, and 16.3% post-implementation). A higher proportion of patients were exacerbation-free post-implementation in the overall asthma population and in the two subgroups. At least 71.5% of patients transitioned to MART were still prescribed MART 12 months post-implementation, of whom ≥86.7% were SABA-free. Conclusion: SENTINEL implementation led to reduced SABA prescribing, increased inhaled corticosteroid uptake and fewer asthma exacerbations. MART was considered appropriate for ∼50% of reviewed patients, with improved prescribing patterns sustained post-implementation.

Polymorphonuclear neutrophils (PMNs) play a critical role in clearing invading microbes and promoting tissue repair following infection/injury. However, dysregulated PMN trafficking and associated tissue damage is pathognomonic of numerous inflammatory mucosal diseases. The final step in PMN influx into mucosal lined organs (including the lungs, kidneys, skin, and gut) involves transepithelial migration (TEpM). The β2-integrin CD11b/CD18 plays an important role in mediating PMN intestinal trafficking, with recent studies highlighting that terminal fucose and GlcNAc glycans on CD11b/CD18 can be targeted to reduce TEpM. However, the role of the most abundant terminal glycan, sialic acid (Sia), in regulating PMN epithelial influx and mucosal inflammatory function is not well understood. Here we demonstrate that inhibiting sialidase-mediated removal of α2-3–linked Sia from CD11b/CD18 inhibits PMN migration across intestinal epithelium in vitro and in vivo. Sialylation was also found to regulate critical PMN inflammatory effector functions, including degranulation and superoxide release. Finally, we demonstrate that sialidase inhibition reduces bacterial peptide–mediated CD11b/CD18 activation in PMN and blocks downstream intracellular signaling mediated by spleen tyrosine kinase (Syk) and p38 MAPK. These findings suggest that sialylated glycans on CD11b/CD18 represent potentially novel targets for ameliorating PMN-mediated tissue destruction in inflammatory mucosal diseases.

Methane seeps are highly abundant marine habitats that contribute sources of chemosynthetic primary production to marine ecosystems. Seeps also factor into the global budget of methane, a potent greenhouse gas. Because of these factors, methane seeps influence not only local ocean ecology, but also biogeochemical cycles on a greater scale. Methane seeps host specialized microbial communities that vary significantly based on geography, seep gross morphology, biogeochemistry, and a diversity of other ecological factors including cross-domain species interactions. In this study, we collected sediment cores from six seep and non-seep locations from Grays and Quinault Canyons (46–47°N) off Washington State, USA, as well as one non-seep site off the coast of Oregon, USA (45°N) to quantify the scale of seep influence on biodiversity within marine habitats. These samples were profiled using 16S rRNA gene sequencing. Predicted gene functions were generated using the program PICRUSt2, and the community composition and predicted functions were compared among samples. The microbial communities at seeps varied by seep morphology and habitat, whereas the microbial communities at non-seep sites varied by water depth. Microbial community composition and predicted gene function clearly transitioned from on-seep to off-seep in samples collected from transects moving away from seeps, with a clear ecotone and high diversity where methane-fueled habitats transition into the non-seep deep sea. Our work demonstrates the microbial and metabolic sphere of influence that extends outwards from methane seep habitats.

Abstract Background Interventions designed to increase mental health awareness in sport have grown substantially in the last 5 years, meaning that those involved in policy, research and intervention implementation are not fully informed by the latest systematic evaluation of research, risking a disservice to healthcare consumers. Hence, our aim was to update a 2017 systematic review that determined the effect of sport-specific mental health awareness programmes to improve mental health knowledge and help-seeking among sports coaches, athletes and officials. We extended the review to incorporate parents as a source of help-seeking and report the validity of outcome measures and quality of research design that occurred since the original review. Methods Sport-specific mental health awareness programmes adopting an experimental or quasi-experimental design were included for synthesis. Five electronic databases were searched: Psychinfo, Medline (OVID interface), Scopus, Cochrane and Cinahl. Each database was searched from its year of inception to June 2020. As all of the outcomes measured were derived from psychometric scales, we observed statistically significant quantitative effects on the basis of p < .05, and a small, medium or large effect size as d = .2, .5 or .8, respectively. Risk of bias was assessed using the Cochrane and QATSQ tools. Results Twenty-eight articles were included from the 2048 retrieved, eighteen additional articles since the original review. Eighteen studies targeted athletes, five with coaches, one sport officials (i.e. referees), one ‘at-risk children’ and three with parents. One of the studies was a combination of athletes, coaches and parents. In terms of study outcomes, health referral efficacy was improved in seven studies; twelve studies reported an increase in knowledge about mental health disorders. Proportionally, higher quality research designs were evident, as three of ten studies within the previous review did not demonstrate a high risk of bias, whereas thirteen of the eighteen additional studies did not display a high risk of bias. However, only one study included a behaviour change model in both the programme design and evaluation. Conclusions Our updated systematic review provides evidence of the benefits of mental health awareness interventions in sport; these benefits are mainly for athletes and show improvements in the methodological design of recent studies compared to the first review. There was also evidence of the extension of programme delivery to parents. In conclusion, researchers, practitioners and policy makers should consider methodological guidance and the application of theory when developing and evaluating complex interventions. Systematic review registration PROSPERO CRD42016040178

People with HIV (PWH) incur a higher risk of COVID-19-related morbidity and mortality rates, yet less is known about COVID-19 vaccine uptake and hesitancy in this group. We conducted a cross-sectional study in Freetown, Sierra Leone, from April to June 2022, using the VAX scale, a validated instrument, to assess attitudes towards COVID-19 vaccination and calculate the hesitancy (VAX) scores. We used generalized linear models to identify the factors associated with vaccine hesitancy. Overall, 490 PWH were enrolled (71.4% female, median age: 38 years, median CD4 count: 412 cells/mm3). About 17.3% received ≥1 dose of a COVID-19 vaccine. The mean VAX score was 43.14 ± 7.05, corresponding to 59.9% participants being vaccine-hesitant. A preference for natural immunity (65.8%) and concerns about profiteering (64.4%) were the commonest reasons for hesitancy, followed by a mistrust of vaccine benefits (61.4%) and worries about future effects (48.0%). In the adjusted regression analysis, being a Muslim (β = 2.563, p < 0.001) and having an urban residence (β = 1.709, p = 0.010) were associated with greater vaccine hesitancy, while testing for COVID-19 was associated with reduced vaccine hesitancy (β = −3.417, p = 0.027). These findings underscore the importance of addressing vaccine hesitancy as a critical element boosting COVID-19 vaccine uptake among PWH.

State and local health departments established the California Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Respiratory Virus Sentinel Surveillance System to conduct enhanced surveillance for SARS-CoV-2 and other respiratory pathogens at sentinel outpatient testing sites in 10 counties throughout California, USA. We describe results obtained during May 10, 2020‒June 12, 2021, and compare persons with positive and negative SARS-CoV-2 PCR results by using Poisson regression. We detected SARS-CoV-2 in 1,696 (19.6%) of 8,662 specimens. Among 7,851 specimens tested by respiratory panel, rhinovirus/enterovirus was detected in 906 (11.5%) specimens and other respiratory pathogens in 136 (1.7%) specimens. We also detected 23 co-infections with SARS-CoV-2 and another pathogen. SARS-CoV-2 positivity was associated with male participants, an age of 35–49 years, Latino race/ethnicity, obesity, and work in transportation occupations. Sentinel surveillance can provide useful virologic and epidemiologic data to supplement other disease monitoring activities and might become increasingly useful as routine testing decreases.

Ocular surface diseases, including conjunctivitis, are recognized as common comorbidities in atopic dermatitis (AD) and occur at an increased frequency in patients with AD treated with biologics targeting IL-4 receptor α (IL-4Rα) or IL-13. However, the inflammatory mechanisms underlying this pathology are unknown. Here, we developed a potentially novel mouse model of skin inflammation–evoked conjunctivitis and showed that it is dependent on CD4+ T cells and basophils. Blockade of IL-4Rα partially attenuated conjunctivitis development, downregulated basophil activation, and led to a reduction in expression of genes related to type 2 cytokine responses. Together, these data suggest that an IL-4Rα/basophil axis plays a role in the development of murine allergic conjunctivitis. Interestingly, we found a significant augmentation of a number of genes that encode tear proteins and enzymes in anti–IL-4Rα–treated mice, and it may underlie the partial efficacy in this model and may represent candidate mediators of the increased frequency of conjunctivitis following dupilumab in patients with AD.

BackgroundThere is little information on the epidemiology of enteric pathogens in Lebanon, a low- and middle-income country that suffers from a myriad of public health challenges. To address this knowledge gap, we aimed to assess the prevalence of enteric pathogens, identify risk factors and seasonal variations, and describe associations between pathogens among diarrheic patients in the Lebanese community.Methodology and principal findingsA multicenter cross-sectional community-based study was conducted in the north of Lebanon. Stool samples were collected from 360 outpatients suffering from acute diarrhea. Based on fecal examination using the BioFire® FilmArray® Gastrointestinal Panel assay, the overall prevalence of enteric infections was 86.1%. Enteroaggregative Escherichia coli (EAEC) was the most frequently identified (41.7%), followed by enteropathogenic E. coli (EPEC) (40.8%) and rotavirus A (27.5%). Notably, two cases of Vibrio cholerae were identified, while Cryptosporidium spp. (6.9%) was the most common parasitic agent. Overall, 27.7% (86/310) of the cases were single infections, and the majority, 73.3% (224/310), were mixed infections. Multivariable logistic regression models showed that enterotoxigenic E. coli (ETEC) and rotavirus A infections were significantly more likely to occur in the fall and winter compared to the summer. Rotavirus A infections significantly decreased with age but increased in patients living in rural areas or suffering from vomiting. We identified strong associations in the co-occurrence of EAEC, EPEC, and ETEC infections and a higher percentage of rotavirus A and norovirus GI/GII infections among EAEC-positive cases.ConclusionsSeveral of the enteric pathogens reported in this study are not routinely tested in Lebanese clinical laboratories. However, anecdotal evidence suggests that diarrheal diseases are on the rise due to widespread pollution and the deterioration of the economy. Therefore, this study is of paramount importance to identify circulating etiologic agents and prioritize dwindling resources to control them and limit outbreaks in the future.

Abstract Our goal is to explore quantitative motor features in critically ill patients with severe brain injury (SBI). We hypothesized that computational decoding of these features would yield information on underlying neurological states and outcomes. Using wearable microsensors placed on all extremities, we recorded a median 24.1 (IQR: 22.8–25.1) hours of high-frequency accelerometry data per patient from a prospective cohort (n = 69) admitted to the ICU with SBI. Models were trained using time-, frequency-, and wavelet-domain features and levels of responsiveness and outcome as labels. The two primary tasks were detection of levels of responsiveness, assessed by motor sub-score of the Glasgow Coma Scale (GCSm), and prediction of functional outcome at discharge, measured with the Glasgow Outcome Scale–Extended (GOSE). Detection models achieved significant (AUC: 0.70 [95% CI: 0.53–0.85]) and consistent (observation windows: 12 min–9 h) discrimination of SBI patients capable of purposeful movement (GCSm > 4). Prediction models accurately discriminated patients of upper moderate disability or better (GOSE > 5) with 2–6 h of observation (AUC: 0.82 [95% CI: 0.75–0.90]). Results suggest that time series analysis of motor activity yields clinically relevant insights on underlying functional states and short-term outcomes in patients with SBI.

BackgroundThe benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains unclear. The objective of this study was to estimate the effectiveness of primary (two-dose series) and booster (third dose) mRNA vaccination against Omicron (lineage BA.1) infection among people with a prior documented infection.Methods and findingsWe conducted a test-negative case-control study of reverse transcription PCRs (RT-PCRs) analyzed with the TaqPath (Thermo Fisher Scientific) assay and recorded in the Yale New Haven Health system from November 1, 2021, to April 30, 2022. Overall, 11,307 cases (positive TaqPath analyzed RT-PCRs with S-gene target failure [SGTF]) and 130,041 controls (negative TaqPath analyzed RT-PCRs) were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 5.9% and 8.1% had a documented prior infection (positive SARS-CoV-2 test record ≥90 days prior to the included test), respectively. We estimated the effectiveness of primary and booster vaccination relative to SGTF-defined Omicron (lineage BA.1) variant infection using a logistic regression adjusted for date of test, age, sex, race/ethnicity, insurance, comorbidities, social venerability index, municipality, and healthcare utilization. The effectiveness of primary vaccination 14 to 149 days after the second dose was 41.0% (95% confidence interval (CI): 14.1% to 59.4%, p 0.006) and 27.1% (95% CI: 18.7% to 34.6%, p < 0.001) for people with and without a documented prior infection, respectively. The effectiveness of booster vaccination (≥14 days after booster dose) was 47.1% (95% CI: 22.4% to 63.9%, p 0.001) and 54.1% (95% CI: 49.2% to 58.4%, p < 0.001) in people with and without a documented prior infection, respectively. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds of infection among boosted (≥14 days after booster dose) and booster-eligible people (≥150 days after second dose). The odds ratio (OR) comparing boosted and booster-eligible people with a documented prior infection was 0.79 (95% CI: 0.54 to 1.16, p 0.222), whereas the OR comparing boosted and booster-eligible people without a documented prior infection was 0.54 (95% CI: 0.49 to 0.59, p < 0.001). This study's limitations include the risk of residual confounding, the use of data from a single system, and the reliance on TaqPath analyzed RT-PCR results.ConclusionsIn this study, we observed that primary vaccination provided significant but limited protection against Omicron (lineage BA.1) infection among people with and without a documented prior infection. While booster vaccination was associated with additional protection against Omicron BA.1 infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection. These findings support primary vaccination in people regardless of documented prior infection status but suggest that infection history may impact the relative benefit of booster doses.

Background: Over a life course, human adaptive immunity to antigenically mutable pathogens exhibits competitive and facilitative interactions. We hypothesize that such interactions may lead to cyclic dynamics in immune responses over a lifetime. Methods: To investigate the cyclic behavior, we analyzed hemagglutination inhibition titers against 21 historical influenza A(H3N2) strains spanning 47 years from a cohort in Guangzhou, China, and applied Fourier spectrum analysis. To investigate possible biological mechanisms, we simulated individual antibody profiles encompassing known feedbacks and interactions due to generally recognized immunological mechanisms. Results: We demonstrated a long-term periodicity (about 24 years) in individual antibody responses. The reported cycles were robust to analytic and sampling approaches. Simulations suggested that individual-level cross-reaction between antigenically similar strains likely explains the reported cycle. We showed that the reported cycles are predictable at both individual and birth cohort level and that cohorts show a diversity of phases of these cycles. Phase of cycle was associated with the risk of seroconversion to circulating strains, after accounting for age and pre-existing titers of the circulating strains. Conclusions: Our findings reveal the existence of long-term periodicities in individual antibody responses to A(H3N2). We hypothesize that these cycles are driven by preexisting antibody responses blunting responses to antigenically similar pathogens (by preventing infection and/or robust antibody responses upon infection), leading to reductions in antigen-specific responses over time until individual’s increasing risk leads to an infection with an antigenically distant enough virus to generate a robust immune response. These findings could help disentangle cohort effects from individual-level exposure histories, improve our understanding of observed heterogeneous antibody responses to immunizations, and inform targeted vaccine strategy. Funding: This study was supported by grants from the NIH R56AG048075 (DATC, JL), NIH R01AI114703 (DATC, BY), the Wellcome Trust 200861/Z/16/Z (SR), and 200187/Z/15/Z (SR). This work was also supported by research grants from Guangdong Government HZQB-KCZYZ-2021014 and 2019B121205009 (YG and HZ). DATC, JMR and SR acknowledge support from the National Institutes of Health Fogarty Institute (R01TW0008246). JMR acknowledges support from the Medical Research Council (MR/S004793/1) and the Engineering and Physical Sciences Research Council (EP/N014499/1). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The Abbott BinaxNOW rapid antigen test is cheaper and faster than real-time reverse transcription PCR (rRT-PCR) for detecting severe acute respiratory syndrome coronavirus 2. We compared BinaxNOW with rRT-PCR in 769 paired specimens from 342 persons during a coronavirus disease outbreak among horse racetrack workers in California, USA. We found positive percent agreement was 43.3% (95% CI 34.6%–52.4%), negative percent agreement 100% (95% CI 99.4%–100%), positive predictive value 100% (95% CI 93.5%–100%), and negative predictive value 89.9% (95% CI 87.5%–92.0%). Among 127 rRT-PCR–positive specimens, the 55 with paired BinaxNOW-positive results had a lower mean cycle threshold than the 72 with paired BinaxNOW-negative results (17.8 vs. 28.5; p

Abstract A novel Gram-stain negative, aerobic, halotolerant, motile, rod-shaped, predatory bacterium ASxL5T, was isolated from a bovine slurry tank in Nottinghamshire, UK using Campylobacter hyointestinalis as prey. Other Campylobacter species and members of the Enterobacteriaceae were subsequently found to serve as prey. Weak axenic growth on Brain Heart Infusion agar was achieved upon subculture without host cells. The optimal growth conditions were 37 °C, at pH 7. Transmission electron microscopy revealed some highly unusual morphological characteristics related to prey availability. Phylogenetic analyses using 16S rRNA gene sequences showed that the isolate was related to members of the Oceanospirillaceae family but could not be classified clearly as a member of any known genus. Whole genome sequencing of ASxL5T confirmed the relationship to members the Oceanospirillaceae. Database searches revealed that several ASxL5T share 16S rRNA gene sequences with several uncultured bacteria from marine, and terrestrial surface and subsurface water. We propose that strain ASxL5T represents a novel species in a new genus. We propose the name Venatorbacter cucullus gen. nov., sp. nov. with ASxL5T as the type strain.