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BackgroundPrematurity (gestational age AimThis was to find out the proportions of preterm babies who survived at the Special Care Baby Unit (SCBU) in the Cape Coast Teaching Hospital (CCTH) and the factors which influenced their survival.MethodThis was a retrospective review of data on all the live preterm babies seen at the SCBU of CCTH from 2010 to 2019. Data on 2,254 babies that met the inclusion criteria were extracted. Descriptive statistics were generated and tests of association done with chi-square and multivariable logistic regression.OutcomeThe main outcome measure was the proportion of live preterm neonates who were discharged after SCBU admissions.ResultsThe CCTH had a total of 27,320 deliveries from 2010 to 2019. Of these, 1,282 were live preterm births, giving a prevalence of live preterm babies over the ten-year period of 4.7% (1,282/27,320). An increasing trend in prevalence was observed with 2019 recording the highest at 9% (271/3027). Most (48.8%) of the deliveries were vaginal, 39.2% were by caesarean section (CS); the mode of birth for 12% of the women were not documented. The mean gestational age was 31.8 (±2.77) weeks. Of the birth weights documented, 2500g made up only 3.7%. The average length of hospital stay was 8.3 (±9.88) days. Regarding the main outcome variable, 67.6% were discharged alive, 27.6% died and 4.9% were unaccounted for due to incomplete documentation. Factors which influenced survival were: birth weight (p ConclusionThis study shows the possibility of achieving good preterm survival rates through the provision of specialised neonatal care, even in resource-constrained countries. This provides an updated benchmark for clinical decision-making and antenatal counselling. It also highlights the problem of inadequate data capture in our part of the world, which needs considerable improvement.

Dengue fever is a mosquito-borne illness that infects 390 million people annually. Dengue outbreaks in Guatemala have been occurring more often and at increased rates since the first dengue outbreak in Guatemala in the 1970s. This study will examine environmental and socioeconomic factors associated with dengue in Guatemala at the municipality (county) level. Socioeconomic factors included population density, Mayan population, economic activity, and attending school. Environmental factors included average minimum annual temperature and annual precipitation. The relationship between environmental and socioeconomic variables and dengue fever incidence was initially evaluated through univariate zero-inflated negative binomial models, and then again through three zero-inflated multivariate negative binomial regression models. For all three models, elevation was considered a predictor of zero-inflation. In the combined model, there was a positive relationship between minimum temperature, economic activity and dengue fever incidence, and a negative relationship between population density, Mayan population and dengue fever. Predicted rates of dengue fever incidence and adjusted confidence intervals were calculated after increasing minimum yearly temperature by 1°C and 2°C. The three municipalities with the highest minimum yearly temperature (El Estor, Iztapa, and Panzós) and the municipality of Guatemala, all had an increase in the magnitude of the risk of dengue fever incidence following 1°C and 2°C increase in temperature. This research suggests that these socioeconomic and environmental factors are associated with risk of dengue in Guatemala. The predicted rates of dengue fever also highlight the potential effect that climate change in the form of increasing temperature can have on dengue in Guatemala.

INTRODUCTION: The fibrous posterior atlanto-occipital membrane (PAOM) at the craniocervical junction is typically removed during decompression surgery for Chiari malformation type I (CM-I); however, its importance and ultrastructural architecture have not been investigated in children. We hypothesized that there are structural differences in the PAOM of patients with CM-I and those without. METHODS: In this prospective study, blinded pathological analysis was performed on PAOM specimens from children who had surgery for CM-I and children who had surgery for posterior fossa tumors (controls). Clinical and radiographic data were collected. Statistical analysis included comparisons between the CM-I and control cohorts and correlations with imaging measures. RESULTS: A total of 35 children (mean age at surgery 10.7 years; 94.3% white) with viable specimens for evaluation were enrolled: 24 with CM-I and 11 controls. There were no statistical demographic differences between the two cohorts. Four children had a family history of CM-I and five had a syndromic condition. The cohorts had similar measurements of tonsillar descent, syringomyelia, basion to C2, and condylar-to-C2 vertical axis (all p>0.05). The clival-axial angle was lower in patients with CM-I (138.1 vs. 149.3 degrees, p = 0.016). Morphologically, the PAOM demonstrated statistically higher proportions of disorganized architecture in patients with CM-I (75.0% vs. 36.4%, p = 0.012). There were no differences in PAOM fat, elastin, or collagen percentages overall and no differences in imaging or ultrastructural findings between male and female patients. Posterior fossa volume was lower in children with CM-I (163,234 mm3 vs. 218,305 mm3, p

[This corrects the article DOI: 10.1371/journal.pone.0240437.].

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

IntroductionThe NIH All of Us Research Program will have the scale and scope to enable research for a wide range of diseases, including cancer. The program's focus on diversity and inclusion promises a better understanding of the unequal burden of cancer. Preliminary cancer ascertainment in the All of Us cohort from two data sources (self-reported versus electronic health records (EHR)) is considered.Materials and methodsThis work was performed on data collected from the All of Us Research Program's 315,297 enrolled participants to date using the Researcher Workbench, where approved researchers can access and analyze All of Us data on cancer and other diseases. Cancer case ascertainment was performed using data from EHR and self-reported surveys across key factors. Distribution of cancer types and concordance of data sources by cancer site and demographics is analyzed.Results and discussionData collected from 315,297 participants resulted in 13,298 cancer cases detected in the survey (in 89,261 participants), 23,520 cancer cases detected in the EHR (in 203,813 participants), and 7,123 cancer cases detected across both sources (in 62,497 participants). Key differences in survey completion by race/ethnicity impacted the makeup of cohorts when compared to cancer in the EHR and national NCI SEER data.ConclusionsThis study provides key insight into cancer detection in the All of Us Research Program and points to the existing strengths and limitations of All of Us as a platform for cancer research now and in the future.

BackgroundIn the absence of universal testing, effective therapies, or vaccines, identifying risk factors for viral infection, particularly readily modifiable exposures and behaviors, is required to identify effective strategies against viral infection and transmission.MethodsWe conducted a world-wide mobile application-based prospective cohort study available to English speaking adults with a smartphone. We collected self-reported characteristics, exposures, and behaviors, as well as smartphone-based geolocation data. Our main outcome was incident symptoms of viral infection, defined as fevers and chills plus one other symptom previously shown to occur with SARS-CoV-2 infection, determined by daily surveys.FindingsAmong 14, 335 participants residing in all 50 US states and 93 different countries followed for a median 21 days (IQR 10-26 days), 424 (3%) developed incident viral symptoms. In pooled multivariable logistic regression models, female biological sex (odds ratio [OR] 1.75, 95% CI 1.39-2.20, p

BackgroundExisting social relationships are a potential source of "social capital" that can enhance support for sustained retention in HIV care. A previous pilot study of a social network-based 'microclinic' intervention, including group health education and facilitated HIV status disclosure, reduced disengagement from HIV care. We conducted a pragmatic randomized trial to evaluate microclinic effectiveness.MethodsIn nine rural health facilities in western Kenya, we randomized HIV-positive adults with a recent missed clinic visit to either participation in a microclinic or usual care (NCT02474992). We collected visit data at all clinics where participants accessed care and evaluated intervention effect on disengagement from care (≥90-day absence from care after a missed visit) and the proportion of time patients were adherent to clinic visits ('time-in-care'). We also evaluated changes in social support, HIV status disclosure, and HIV-associated stigma.ResultsOf 350 eligible patients, 304 (87%) enrolled, with 154 randomized to intervention and 150 to control. Over one year of follow-up, disengagement from care was similar in intervention and control (18% vs 17%, hazard ratio 1.03, 95% CI 0.61-1.75), as was time-in-care (risk difference -2.8%, 95% CI -10.0% to +4.5%). The intervention improved social support for attending clinic appointments (+0.4 units on 5-point scale, 95% CI 0.08-0.63), HIV status disclosure to close social supports (+0.3 persons, 95% CI 0.2-0.5), and reduced stigma (-0.3 units on 5-point scale, 95% CI -0.40 to -0.17).ConclusionsThe data from our pragmatic randomized trial in rural western Kenya are compatible with the null hypothesis of no difference in HIV care engagement between those who participated in a microclinic intervention and those who did not, despite improvements in proposed intervention mechanisms of action. However, some benefit or harm cannot be ruled out because the confidence intervals were wide. Results differ from a prior quasi-experimental pilot study, highlighting important implementation considerations when evaluating complex social interventions for HIV care.Trial registrationClinical trial number: NCT02474992.

BackgroundThe concept of 'child marriage' in global health distinguishes ostensibly harmful from healthy ages to marry at a universally-applied threshold of 18-years. With intensifying efforts to end child marriage, targeted communities are increasingly asked to change their perception of such marriages from relatively benign to profoundly problematic. The objective of this study is to understand how this shift in perception is navigated by adolescent girls and young women (AGYW).MethodsUsing qualitative data collected in 2019 from a semi-urban community in Tanzania where marriage under 18-years is common and campaigns to end child marriage ongoing, we contrast reports of lived experiences of marriage under 18-years among AGYW to views of child marriage as an abstract concept. Thirteen in-depth interviews with AGYW, as part of a wider qualitative study, were recorded, transcribed, and analyzed using a framework analysis approach.ResultsWhile many AGYW had heard of child marriage, the concept was routinely conflated with forced marriage, which is rare in the community, and non-marital teenage sex and pregnancy, which are common. As a likely consequence, participants disagreed on whether or not child marriage occurs locally. Furthermore, accounts of real-life marriages under 18 sometimes aligned with, but often departed from, common narratives about the purported causes and harmful consequences inherent to the global health concept of child marriage.ConclusionsWe argue that engaging with diverse local views and experiences of marrying young is essential to producing culturally-sensitive, effective initiatives addressing the vulnerabilities of female adolescence.

Recently emerging evidence indicates accelerated age-related changes in the structure and function of the brain in schizophrenia, raising a question about its potential consequences on cognitive function. Using a large sample of schizophrenia patients and controls and a battery of tasks across multiple cognitive domains, we examined whether patients show accelerated age-related decline in cognition and whether an age-related effect differ between females and males. We utilized data of 1,415 schizophrenia patients and 1,062 healthy community collected by the second phase of the Consortium on the Genetics of Schizophrenia (COGS-2). A battery of cognitive tasks included the Letter-Number Span Task, two forms of the Continuous Performance Test, the California Verbal Learning Test, Second Edition, the Penn Emotion Identification Test and the Penn Facial Memory Test. The effect of age and gender on cognitive performance was examined with a general linear model. We observed age-related changes on most cognitive measures, which was similar between males and females. Compared to controls, patients showed greater deterioration in performance on attention/vigilance and greater slowness of processing social information with increasing age. However, controls showed greater age-related changes in working memory and verbal memory compared to patients. Age-related changes (η2p of 0.001 to .008) were much smaller than between-group differences (η2p of 0.005 to .037). This study found that patients showed continued decline of cognition on some domains but stable impairment or even less decline on other domains with increasing age. These findings indicate that age-related changes in cognition in schizophrenia are subtle and not uniform across multiple cognitive domains.

BackgroundPoor diets contribute to metabolic complications of obesity, insulin resistance and dyslipidemia. Metabolomic biomarkers may serve as early nutrition-sensitive health indicators. This family-based lifestyle change program compared metabolic outcomes in an intervention group (INT) that consumed 2 nutrient bars daily for 2-months and a control group (CONT).MethodsOverweight, predominantly minority and female adolescent (Teen)/parent adult caretaker (PAC) family units were recruited from a pediatric obesity clinic. CONT (8 Teen, 8 PAC) and INT (10 Teen, 10 PAC) groups randomized to nutrient bar supplementation attended weekly classes that included group nutrition counseling and supervised exercise. Pre-post physical and behavioral parameters, fasting traditional biomarkers, plasma sphingolipids and amino acid metabolites were measured.ResultsIn the full cohort, a baseline sphingolipid ceramide principal component composite score correlated with adiponectin, triglycerides, triglyceride-rich very low density lipoproteins, and atherogenic small low density lipoprotein (LDL) sublasses. Inverse associations were seen between a sphingomyelin composite score and C-reactive protein, a dihydroceramide composite score and diastolic blood pressure, and the final principal component that included glutathionone with fasting insulin and the homeostatic model of insulin resistance. In CONT, plasma ceramides, sphinganine, sphingosine and amino acid metabolites increased, presumably due to increased physical activity. Nutrient bar supplementation (INT) blunted this rise and significantly decreased ureagenic, aromatic and gluconeogenic amino acid metabolites. Metabolomic changes were positively correlated with improvements in clinical biomarkers of dyslipidemia.ConclusionNutrient bar supplementation with increased physical activity in obese Teens and PAC elicits favorable metabolomic changes that correlate with improved dyslipidemia. The trial from which the analyses reported upon herein was part of a series of nutrient bar clinical trials registered at clinicaltrials.gov as NCT02239198.

BACKGROUND: Integrated cardiovascular disease (CVD) and HIV (CVD-HIV) care interventions are being adopted to tackle the growing burden of noncommunicable diseases (NCDs) in low-and middle-income countries (LMICs) but there is a paucity of studies on the feasibility of these interventions in LMICs. This scoping review aims to present evidence of the feasibility of integrated CVD-HIV care in LMICs, and the alignment of feasibility reporting in LMICs with the existing implementation science methodology. METHODS: A systematic search of published articles including systematic and narrative reviews that reported on integrated CVD-HIV care was conducted, using multiple search engines including PubMed/Medline, Global Health, and Web of Science. We examined the articles for evidence of feasibility reporting. Adopting the definition of Proctor and colleagues (2011), feasibility was defined as the extent to which an intervention was plausible in a given agency or setting. Evidence from the articles was synthesized by level of integration, the chronic care continuum, and stages of intervention development. RESULTS: Twenty studies, reported in 18 articles and 3 conferences abstracts, reported on feasibility of integrated CVD-HIV care interventions. These studies were conducted in Sub-Saharan Africa, Southeast Asia and South America. Four of these studies were conducted as feasibility studies. Eighty percent of the studies reported feasibility, using descriptive sentences that included words synonymous with feasibility terminologies in existing definition recommended by Proctor and colleagues. There was also an overlap in the use of descriptive phrases for feasibility amongst the selected studies. CONCLUSIONS: Integrating CVD and HIV care is feasible in LMICs, although methodology for reporting feasibility is inconsistent. Assessing feasibility based on settings and integration goals will provide a unique perspective of the implementation landscape in LMICs. There is a need for consistency in measures in order to accurately assess the feasibility of integrated CVD-HIV care in LMICs.

BACKGROUND: The Primary HIV Prevention among Pregnant and Lactating Ugandan Women (PRIMAL) study aimed to assess the effectiveness of an enhanced HIV counseling intervention for preventing HIV acquisition among HIV-uninfected mothers during pregnancy and throughout the breastfeeding period. METHODS: We conducted an unblinded randomized control trial between 22 February 2013 and 22 April 2016 to assess the effectiveness of an extended repeat HIV testing and enhanced counseling (ERHTEC) intervention aimed at preventing primary HIV infection among HIV-uninfected pregnant and lactating women in Uganda. HIV-uninfected pregnant women aged 15-49 were enrolled 1:1 individually or in couples together with their partner. Enrolled women and couples were randomized 1:1 to an intervention (ERHTEC) or control (extended repeat HIV testing and standard counseling) group and followed up to 24 months postpartum or six weeks past complete cessation of breastfeeding, whichever came first. Both groups were tested for sexually transmitted infections (STIs) and HIV at enrollment, delivery, 3 and 6 months postpartum and every 6 months thereafter until the end of follow-up. The intervention group received enhanced HIV prevention counseling every 3 months throughout follow-up. The control group received standard counseling at the time of HIV retesting. Both intervention and control couples were offered couple HIV testing and counseling at all study visits. MAIN OUTCOME MEASURES: Frequency of condom use and incidence of HIV, syphilis, gonorrhea, chlamydia and trichomoniasis over follow-up. RESULTS: Between February 2013 and April 2014, we enrolled 820 HIV-uninfected pregnant women presenting for antenatal care individually (n = 410) or in couples (n = 410 women and 410 partners) in one urban and one rural public Ugandan hospital. Womens median age was 24 years (IQR 20-28 years). At baseline, participants did not differ in any socio-demographic, reproductive health, HIV testing history, sexual behavior, medical history or STI status characteristics; 96% (386/402) of couples were tested and counseled for HIV together with their partners at enrolment, 2.1% (7/329) of whom were found to be HIV-infected. Six hundred twenty-five (76%) women completed follow-up as per protocol (S1 Protocol). Women were followed for an average of 1.76 years and cumulated 1,439 women-years of follow-up or 81% of the maximum 1,779 women-years of follow-up assuming no dropouts. Men were followed for an average of 1.72 years. The frequency of consistent condom use and the proportion of women who used condoms over the last 3 months or at last vaginal sex increased substantially over follow-up in both arms, but there were no statistically significant differences in increases between the intervention and control arms. During follow-up, on average 42% (range 36%-46%) of couple partners were counseled together. Between 3.8% and 7.6% of women tested positive at any follow-up visit for any STI including syphilis, gonorrhea, C. trachomatis or T. vaginalis. Four women (two in each arm) and no enrolled men became infected with HIV, representing an overall HIV incidence rate of 0.186 per 100 person-years. Three of the women seroconverters had enrolled individually, one as a couple. At or before seroconversion, all four women reported their partners had extramarital relationships and/or had not disclosed their suspected HIV-infected status. There were no statistically significant differences between study arms for STI or HIV incidences. CONCLUSIONS: A sustained enhanced HIV prevention counseling intervention for up to 2 years postpartum among pregnant and breastfeeding women did not have a statistically significant effect on condom use or HIV incidence among these women. However, in both study arms, condom use increased over follow-up while STI and HIV incidence remained very low when compared to similar cohorts in and outside Uganda, suggesting that repeat HIV testing during breastfeeding, whether with enhanced or standard counseling, may have had an unintended HIV preventive effect among pregnant and lactating women in this setting. Further research is needed to verify this hypothesis. TRIAL REGISTRATION: ClinicalTrials.gov NCT01882998.

The sugarcane borer moth, Diatraea saccharalis, is one of the most important pests of sugarcane and maize crops in the Western Hemisphere. The pest is widespread throughout South and Central America, the Caribbean region and the southern United States. One of the most intriguing features of D. saccharalis population dynamics is the high rate of range expansion reported in recent years. To shed light on the history of colonization of D. saccharalis, we investigated the genetic structure and diversity in American populations using single nucleotide polymorphism (SNPs) markers throughout the genome and sequences of the mitochondrial gene cytochrome oxidase (COI). Our primary goal was to propose possible dispersal routes from the putative center of origin that can explain the spatial pattern of genetic diversity. Our findings showed a clear correspondence between genetic structure and the geographical distributions of this pest insect on the American continents. The clustering analyses indicated three distinct groups: one composed of Brazilian populations, a second group composed of populations from El Salvador, Mexico, Texas and Louisiana and a third group composed of the Florida population. The predicted time of divergence predates the agriculture expansion period, but the pattern of distribution of haplotype diversity suggests that human-mediated movement was most likely the factor responsible for the widespread distribution in the Americas. The study of the early history of D. saccharalis promotes a better understanding of range expansion, the history of invasion, and demographic patterns of pest populations in the Americas.

Public and patient involvement (PPI) has been identified as an increasingly desired and, often, required component of trial methodology–leading to higher quality, more accessible and relevant clinical research, alongside increased recruitment, funding success and insight into research impact. However, despite the great variety of frameworks and checklists available for assessing PPI, most are limited with respect to important features (e.g. applicable in specific contexts only, fail to clarify what should be assessed and reported, lack the necessary comprehensiveness or are biased in favour of researcher reporting). Thus, the current research aimed to address such limitations through the development of a new checklist, the EPPIIC, through review, thematic analysis and 'meta-evaluation' in conjunction with PPI engagement. Upon completion of the EPPIIC, three thematic 'sub-scales' emerged: (1) Policy & Practice, (2) Participatory Culture and (3) Influence & Impact. All findings are presented and discussed in light of theory and research. Notably, findings recommend EPPIIC as a useful means of assessing PPI in future trials. [ABSTRACT FROM AUTHOR]

Female Genital Mutilation/Cutting (FGM/C) and child marriage are prevalent in many countries in Asia and Africa. These practices are a violation of human rights and have significant impacts on the physical and mental well-being of those affected. COVID-19 restrictions such as lockdowns and closure of schools may have influenced the occurrence of FGM/C and child marriage. This analysis reported on the impact of these restrictions on FGM/C and child marriage. The International Sexual Health And REproductive Health (I-SHARE) research team organised a multi-country online survey. Sampling methods included convenience samples, online panels, and population-representative samples. Data collected included the impact of COVID-19 restrictions on the occurrence, intention to practice and change in plans to organise FGM/C and child marriage. Data were analysed from 14 countries that reported on FGM/C and child marriage using basic descriptive statistics. Given it was an online survey, we had more responses from urban areas. Among the 22,724 overall participants, 8,829 participants (38.9%) responded to the survey items on FGM/C and child marriage and were included in this analysis. 249 (3.4%) participants stated that FGM/C occurred in their community during COVID-19. Out of this, COVID-19 affected the plans of 26 (20%) participants intending to organise circumcision and 15% of participants planned to organise FGM/C earlier. People with a worry about finances during COVID-19 were more likely to have an earlier plan to organise FGM/C during COVID-19. In total, 1,429 (13%) participants reported that child marriage occurred in their community. The pandemic affected plans of 52 (13%) participants intending to arrange child marriage and 7.7% (29/384) participants expressed intent to arrange the marriage sooner than planned. People with financial insecurities during COVID-19 were more likely to arrange a child marriage earlier. Thus, our study found that the pandemic impacted plans related to FGM/C and child marriage practices, resulting in many carrying out the practices sooner or later than initially planned. [ABSTRACT FROM AUTHOR]

Background: Nurturing physical literacy in young children offers a unique opportunity to address global physical inactivity trend. Early childhood education and care (ECEC) environments, with their extensive reach into this age group, and early childhood educators, through their daily interactions with children, are strategically positioned to influence children's physical literacy development. However, enhancing educators' ability to foster physical literacy requires valid and reliable assessment tools to measure holistic physical literacy constructs (i.e., cognitive, affective, behavioral) to assess the impact of physical literacy educational interventions. Objective: The purpose of this study was to develop a holistic digital tool to measure physical literacy knowledge, attitudes, self-efficacy, and behaviors of early childhood educators (PLKASB-ECE) for both their professional teaching context as well as the educator's own personal physical literacy behaviours. Methods: This study was conducted in two phases. Phase 1 involved item generation and content validation. Phase 2 employed a cross-sectional validation study design to assess the psychometric properties of the PLKASB-ECE tool. Results: Based on a literature review an initial 19-item instrument was developed that subsequently underwent three rounds of expert content validation. Six additional items were added, resulting in a final 25-item self-report measure with a readability score equivalent to an 8th grade reading level (Flesch-Kincaid Grade Level: 8.7). This included 1 global rating item, 2 qualitative response items, 7 knowledge items, and 15 items addressing physical literacy attitudes, self-efficacy and behaviors using a 7-point Likert response scale. The PLKASB-ECE tool was administered to 470 educators in Alberta, Canada between 2019 to 2022. The 15 items were subjected to exploratory factor analysis and resulted in a five-factor scale with one item not loading. The five-factor scale held with the final 14 items with loadings ranging from 0.481 to 0.886, Cronbach's alpha ranging from 0.70 to 0.82, with ordinal omega ranging from 0.72 to 0.82. Usability, as assessed by completion time, was 8.15 minutes. Conclusion: These findings demonstrate good indices of reliability and validity for the PLKASB-ECE tool. This tool will be valuable as a research outcome measure for assessing educational interventions aimed at enhancing educators' understanding, confidence, and strategies for fostering holistic concepts of physical literacy in young children within ECECs. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is a keystone pathogen for periodontal disease. The bacteria are black-pigmented and require heme for growth. P. gingivalis exhibit resistance to many antimicrobial peptides, which contributes to their success in the oral cavity. P. gingivalis W50 was resistant to the antimicrobial peptide LGL13K but susceptible to the all-D-amino acid stereoisomer, DGL13K. Upon prolonged exposure to DGL13K, a novel non-pigmented mutant was isolated. Exposure to the L-isomer, LGL13K, did not produce a non-pigmented mutant. The goal of this study was to characterize the genomic and cellular changes that led to the non-pigmented phenotype upon treatment with DGL13K. The non-pigmented mutant showed a low minimum inhibitory concentration and two-fold extended minimum duration for killing by DGL13K, consistent with tolerance to this peptide. The DGL13K-tolerant bacteria exhibited synonymous mutations in the hagA gene. The mutations did not prevent mRNA expression but were predicted to alter mRNA structure. The non-pigmented bacteria were deficient in hemagglutination and hemoglobin binding, suggesting that the HagA protein was not expressed. This was supported by whole cell enzyme-linked immunosorbent assay and gingipain activity assays, which suggested the absence of HagA but not of two closely related gingipains. In vivo virulence was similar for wild type and non-pigmented bacteria in the Galleria mellonella model. The results suggest that, unlike LGL13K, DGL13K can defeat multiple bacterial resistance mechanisms but bacteria can gain tolerance to DGL13K through mutations in the hagA gene. [ABSTRACT FROM AUTHOR]

Pesticides are chemicals used to enhance crop production. However, their residues can persist and accumulate in various environmental settings. This study assessed the occurrence of pesticide residues and ecological risks in surface water and sediment from the Libga and Builpela dams in northern Ghana. A total of 42 pesticides were analysed. Toxic units were used to assess the acute risk to sediment-dwelling organisms and aquatic biota. Risk quotients were employed to assess the chronic risk to aquatic organisms. Chlorpyrifos, atrazine, profenofos, and chlorfenvinphos were the main chemicals found in surface water. The concentrations were highest near the Builpela dam (0.413μg/L, 2.927μg/L, 0.304μg/L, 0.692μg/L, 0.073μg/L, 0.290μg/L, 0.06μg/L, and absent in the Libga dam). In the sediment, the organophosphates pyrimiphos-methyl and chlorpyrifos were found at high concentrations. They were found in higher quantities in the Libga dam (0.554mg/kg and 0.052mg/kg, respectively) and Builpela dam (0.051mg/kg and 0.043mg/kg, respectively). For organochlorines, p,p'-DDE and p,p'-DDD were the main residues detected at high concentrations. However, concentrations were higher for p,p'-DDD at Builpela than for p,p'-DDE. Additionally, high concentrations of atrazine were detected in this study. The toxic units showed a high acute risk for organisms that live in sediment as a result of chlorpyrifosfos and chlorfenvinphos residues. Similarly, pirimiphos-methyl and chlorfenvinphos, followed by chlorpyrifos, contributed to high acute risk in aquatic invertebrates. Risk quotients showed that both dams had a high long-term risk for aquatic life; however, the risk was higher at the Builpela dam due to Pirimiphos-methyl and Chlorfenvinphos. Ghana's pesticide regulations are less comprehensive and enforcement is often weaker in protecting aquatic organisms. It is recommended to enforce strict limits on pesticide residues. Additionally, there is a need to regularly review and update these regulations based on new scientific data to protect aquatic ecosystems. [ABSTRACT FROM AUTHOR]

Background: In 2020, the Coronavirus disease (COVID-19) triggered the latest wave of anti-Asian discrimination. During the first year of the pandemic, symptoms of depression and anxiety increased seven-fold within Asian Pacific Islander Desi American (APIDA) communities. Among this population, APIDA college students were at particularly high risk for mental health challenges due to COVID-19-related racial discrimination. This study examined the association between COVID-19-related racial discrimination and the mental health of APIDA college students, conceptualizing ethnic identity as a moderator in the association. Methods: Secondary analysis was conducted on data from 2,559 APIDA college students aged 18 to 29 who participated in the Fall and Winter/Spring Cohorts of the 2020–2021 Healthy Minds Study (HMS), a non-probability web-based survey administered to students in higher education in the United States. Descriptive statistics, comparative analysis (e.g., Chi-square and t-test), and multivariable linear regression were conducted using STATA 17.1 (StataCorp LLC, College Station, TX). Survey weights were applied in all analyses. Results: There were significant positive associations between COVID-19-related racial discrimination and symptoms of depression (b = 2.15, p < 0.001) and anxiety (b = 1.81, p < 0.001) among the overall sample. Furthermore, a greater sense of ethnic identity was associated with lower symptoms of depression (b = -0.15, p< 0.001) among the overall sample. Finally, ethnic identity buffered the association between COVID-19-related racial discrimination and symptoms of anxiety among East Asian students and symptoms of both depression and anxiety among Native Hawaiian and Pacific Islander students. In contrast, ethnic identity intensified the association between COVID-19-related racial discrimination and symptoms of depression among Filipino students. Conclusions: The research found that COVID-19-related racial discrimination was associated with increased symptoms of depression and anxiety among the full sample of APIDA college students during the first year of the pandemic. Additionally, higher levels of ethnic identity were associated with decreased depression among the entire group. The striking results on the moderating role of ethnic identity among subgroups call for further research on the ethnic identity development of APIDA college students, to help mitigate the effects of racial discrimination within a variety of systemic, complex, and dynamic sociocultural contexts. [ABSTRACT FROM AUTHOR]

Over-prescribing of proton-pump inhibitors (PPIs) is widely observed in older patients. Clinical findings have showed that deprescribing service significantly decreased inappropriate PPIs utilization. We aimed to examine the cost-effectiveness of PPI deprescribing service from the perspective of Hong Kong public healthcare provider. A decision-analytic model was constructed to examine the clinical and economic outcomes of PPI deprescribing service (deprescribing group) and usual care (UC group) in a hypothetical cohort of older PPI-users aged ≥65 years in the ambulatory care setting. The model inputs were retrieved from literature and public data. The model time-frame was one-year. Base-case analysis and sensitivity analysis were performed. Primary model outcomes were direct medical cost and quality-adjusted life-years (QALYs) loss. In base-case analysis, the deprescribing service (versus UC) reduced total direct medical cost by USD235 and saved 0.0249 QALY per PPI user evaluated. The base-case results were robust to variation of all model inputs in one-way sensitivity analysis. In probabilistic sensitivity analysis, the deprescribing group was accepted as cost-effective (versus the UC group) in 100% of the 10,000 Monte Carlo simulations. In conclusion, the PPI deprescribing service saved QALYs and reduced total direct medical cost in older PPIs users, and showed a high probability to be accepted as the cost-effective option from the perspective of public healthcare provider in Hong Kong. [ABSTRACT FROM AUTHOR]

Background: Enteroendocrine cells (EECs) produce over 20 gut hormones which contribute to intestinal physiology, nutrient metabolism and the regulation of food intake. The objective of this study was to generate a comprehensive transcriptomic map of mouse EECs from the stomach to the rectum. Methods: EECs were purified by flow-cytometry from the stomach, upper small intestine, lower small intestine, caecum and large intestine of NeuroD1-Cre mice, and analysed by single cell RNA sequencing. Regional datasets were analysed bioinformatically and combined into a large cluster map. Findings were validated by L-cell calcium imaging and measurements of CCK secretion in vitro. Results: 20,006 EECs across the full gastrointestinal tract could be subdivided based on their full transcriptome into 10 major clusters, each exhibiting a different pattern of gut hormone expression. EECs from the stomach were largely distinct from those found more distally, even when expressing the same hormone. Cell clustering was also observed when performed only using genes related to GPCR cell signalling, revealing GPCRs predominating in different EEC populations. Mc4r was expressed in 55% of Cck-expressing cells in the upper small intestine, where MC4R agonism was found to stimulate CCK release in primary cultures. Many individual EECs expressed more than one hormone as well as machinery for activation by multiple nutrients, which was supported by the finding that the majority of L-cells exhibited calcium responses to multiple stimuli. Conclusions: This comprehensive transcriptomic map of mouse EECs reveals patterns of GPCR and hormone co-expression that should be helpful in predicting the effects of nutritional and pharmacological stimuli on EECs from different regions of the gut. The finding that MC4R agonism stimulates CCK secretion adds to our understanding of the melanocortin system. [ABSTRACT FROM AUTHOR]

Background: The Australian National Perinatal Data Collection collates all live and stillbirths from States and Territories in Australia. In that database, maternal cigarette smoking is noted twice (smoking <20 weeks gestation; smoking >20 weeks gestation). Cannabis use and other forms of nicotine use, for example vaping and nicotine replacement therapy, are nor reported. The 2021 report shows the rate of smoking for Australian Indigenous mothers was 42% compared with 11% for Australian non-Indigenous mothers. Evidence shows that Indigenous babies exposed to maternal smoking have a higher rate of adverse outcomes compared to non-Indigenous babies exposed to maternal smoking (S1 File). Objectives: The reasons for the differences in health outcome between Indigenous and non-Indigenous pregnancies exposed to tobacco and nicotine is unknown but will be explored in this project through a number of activities. Firstly, the patterns of parental and household tobacco, nicotine and cannabis use and exposure will be mapped during pregnancy. Secondly, a range of biological samples will be collected to enable the first determination of Australian Indigenous people's nicotine and cannabis metabolism during pregnancy; this assessment will be informed by pharmacogenomic analysis. Thirdly, the pharmacokinetic and pharmacogenomic findings will be considered against maternal, placental, foetal and neonatal outcomes. Lastly, an assessment of population health literacy and risk perception related to tobacco, nicotine and cannabis products peri-pregnancy will be undertaken. Methods: This is a community-driven, co-designed, prospective, mixed-method observational study with regional Queensland parents expecting an Australian Indigenous baby and their close house-hold contacts during the peri-gestational period. The research utilises a multi-pronged and multi-disciplinary approach to explore interlinked objectives. Results: A sample of 80 mothers expecting an Australian Indigenous baby will be recruited. This sample size will allow estimation of at least 90% sensitivity and specificity for the screening tool which maps the patterns of tobacco and nicotine use and exposure versus urinary cotinine with 95% CI within ±7% of the point estimate. The sample size required for other aspects of the research is less (pharmacokinetic and genomic n = 50, and the placental aspects n = 40), however from all 80 mothers, all samples will be collected. Conclusions: Results will be reported using the STROBE guidelines for observational studies. Forward: We acknowledge the Traditional Custodians, the Butchulla people, of the lands and waters upon which this research is conducted. We acknowledge their continuing connections to country and pay our respects to Elders past, present and emerging. Notation: In this document, the terms Aboriginal and Torres Strait Islander and Indigenous are used interchangeably for Australia's First Nations People. No disrespect is intended, and we acknowledge the rich cultural diversity of the groups of peoples that are the Traditional Custodians of the land with which they identify and with whom they share a connection and ancestry. [ABSTRACT FROM AUTHOR]

This paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives. The aim of this research is to showcase the variety of questions that reflect the broad scope for historical-ecological research trajectories across scientific disciplines. Historical ecology encompasses research concerned with decadal, centennial, and millennial human-environmental interactions, and the consequences that those relationships have in the formation of contemporary landscapes. Six interrelated themes arose from our consensus-building workshop model: (1) climate and environmental change and variability; (2) multi-scalar, multi-disciplinary; (3) biodiversity and community ecology; (4) resource and environmental management and governance; (5) methods and applications; and (6) communication and policy. The 50 questions represented by these themes highlight meaningful trends in historical ecology that distill the field down to three explicit findings. First, historical ecology is fundamentally an applied research program. Second, this program seeks to understand long-term human-environment interactions with a focus on avoiding, mitigating, and reversing adverse ecological effects. Third, historical ecology is part of convergent trends toward transdisciplinary research science, which erodes scientific boundaries between the cultural and natural.

Introduction: Relapse among individuals with serious mental illnesses in resource-limited contexts, including South Africa, is a significant concern. To date, the risks for relapse among this population is well documented, but little is known about prevention strategies to reduce its occurrence in these resource-limited settings. Therefore, this qualitative study explores the risk factors and strategies for relapse prevention from the patients' and caregivers' perspectives. Methods: We conducted audio-recorded face-to-face in-depth interviews to capture the lived experience of relapse of inpatient study participants with serious mental illness (N = 24) at a public specialized psychiatry hospital in South Africa and their caregivers (N = 6). We conducted an inductive thematic analysis with two pre-specified themes (risk factors for relapse and strategies for prevention), with the codes devised from the data. Results: Six sub-themes were identified from the analysis within the two pre-specified themes(Risk factors and strategies for relapse prevention): personal-related, family-related, and health system-related risk factors and strategies for preventing relapse, respectively. To highlight some essential findings, the importance of motivation for drug adherence, family involvement, and availability of anti-psychotic drugs in public health care were noted. More importantly, this study identified important cultural complexities where traditional healers play a significant role in some cultural understanding and treatment of mental illness, affecting medication adherence. Conclusion: This study calls for people-centered mental health care delivery in a public health system that listens to the voice of concern, including cultural challenges, and implements meaningful support that matters most to the patient and their family/caregivers. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of pelvic floor muscle training (PFMT) on pelvic floor muscle (PFM) function and quality of life (QoL) in women with stress urinary incontinence (SUI) and pelvic organ prolapse (POP). Methods: This study will be a randomized, controlled, parallel, and blinded clinical trial. The final sample will consist of 32 women diagnosed with SUI and cystocele (stage I and II). All volunteers will be assessed and reassessed using the same protocol: assessment form, gynecological examination, functional evaluation of PFM, and questionnaires to assess quality of life, urinary function, and sexual function. All volunteers will be evaluated for satisfaction levels post-treatment. The intervention will be PFMT, totaling 16 sessions to be conducted twice a week. Reevaluation will take place at the end of treatment and 1 month after completion of PFMT. Descriptive analysis and repeated measures ANOVA will be used for result analysis. A significance level of p<0.05 will be considered for all statistical tests. Ethics and dissemination: This study has been submitted to the Ethics in Research Committee of the Federal University of Rio Grande do Norte and approved under protocol number 5.826.563. It has been registered with the Brazilian Clinical Trials Registry ReBec (RBR-49p6g3t). It is expected that these studies will provide a deeper understanding of the efficacy of PFMT in women with SUI and cystocele. Additionally, it aims to provide more insights into the efficacy of PFMT prior to surgery. [ABSTRACT FROM AUTHOR]

Purpose: A lifestyle front office (LFO) in the hospital is a not yet existing, novel concept that can refer patients under treatment in the hospital to community-based lifestyle interventions (CBLI). The aim of this study was to identify implementation barriers and facilitators regarding the implementation of an LFO in the hospital from the perspective of CBLI-professionals and to develop evidence-based implementation strategies to reduce these identified barriers. Methods: We conducted semi-structured interviews until data saturation, with 23 lifestyle professionals working in the community. A semi-structured topic guide was used, inquiring about (1) community-based lifestyle interventions; (2) their views about referral from the LFO; and (3) their preferences, needs and recommendations for collaboration with the LFO in the hospital. The online interviews lasted on average 46 minutes, were audio-recorded and transcribed verbatim. A thematic content analysis was conducted. Found barriers and facilitators regarding the LFO where mapped using the consolidated framework for implementation research (CFIR) whereafter evidence based strategies were developed using the CFIR-Expert Recommendations for Implementing Change Strategy Matching Tool V.1.0 (CFIR-ERIC). Results: Barriers and facilitators were divided into two main themes: 1) barriers and facilitators related to the referral from LFO to CBLI (i.e. financial, cultural, geographical, quality) and 2) barriers and facilitators related to the collaboration between LFO and CBLI (i.e. referral, communication platform and partnership). Thirty-seven implementation strategies concerning 15 barriers were developed and clustered into six overarching strategies: identify referral options, determine qualifications lifestyle professionals, develop support tools, build networks, facilitate learning collaboratives, and optimize workflow. Conclusions: In this study, barriers and facilitators for the development of the LFO were found and matching implementation strategies were developed. Practical improvements, like identifying specific referral options or develop support tools, can be implemented immediately. The implementation of other strategies, like connecting care pathways in basic services, primary, secondary and tertiary care, will take more time and effort to come to full potential. Future research should evaluate all implemented strategies. [ABSTRACT FROM AUTHOR]

Diarrheal diseases are important causes of morbidity and mortality, worldwide. The occurrence of multiple pathogens in stool samples of symptomatic and asymptomatic individuals in resource-limited countries have been repeatedly described. In this study, we assessed the differentiated effects of combined pathogen detections on recorded symptoms. A case-control study was conducted among 620 under-five-year-old children in rural northeastern Tanzania with emphasis of multiple detection. The median age of children was 11 months (IQR = 7, 20), and 52.1% were male. Cases (50.2%, n = 157) were less likely than controls (64.5%, n = 198) to have multiple colonization with gastrointestinal tract (GIT) pathogens. The children's age was positively associated with the likelihood of harboring multiple GIT pathogens [OR, 1.02, 95% CI = 1.01, 1.04]. Shigella spp./enteroinvasive Escherichia coli (EIEC) [OR = 2.80, 95% CI 1.62, 4.83] and norovirus [OR = 2.04, 95% CI 1.23, 3.39] were more common in cases and were strongly associated with diarrhea, while enteroaggregative E. coli (EAEC) [OR = 0.23, 95%CI 0.17–0.33] were more common in controls. Diarrheal diseases in under-five children from rural Tanzania are likely to be due to infections with Shigella spp./EIEC, and norovirus with strongly age-dependent associations. [ABSTRACT FROM AUTHOR]

Chlorpyrifos is an organophosphate pesticide associated with numerous health effects including motor performance decrements. While many studies have focused on the health effects following acute chlorpyrifos poisonings, almost no studies have examined the effects on motoneurons following occupational-like exposures. The main objective of this study was to examine the broad effects of repeated occupational-like chlorpyrifos exposures on spinal motoneuron soma size relative to motor activity. To execute our objective, adult rats were exposed to chlorpyrifos via oral gavage once a day, five days a week for two weeks. Chlorpyrifos exposure effects were assessed either three days or two months following the last exposure. Three days following the last repeated chlorpyrifos exposure, there were transient effects in open-field motor activity and plasma cholinesterase activity levels. Two months following the chlorpyrifos exposures, there were delayed effects in sensorimotor gating, pro-inflammatory cytokines and spinal lumbar motoneuron soma morphology. Overall, these results offer support that subacute repeated occupational-like chlorpyrifos exposures have both short-term and longer-term effects in motor activity, inflammation, and central nervous system mechanisms. [ABSTRACT FROM AUTHOR]

New immune checkpoints are emerging in a bid to improve response rates to immunotherapeutic drugs. The adenosine A2A receptor (A2AR) has been proposed as a target for immunotherapeutic development due to its participation in immunosuppression of the tumor microenvironment. Blockade of A2AR could restore tumor immunity and, consequently, improve patient outcomes. Here, we describe the discovery of a potent, selective, and tumor-suppressing antibody antagonist of human A2AR (hA2AR) by phage display. We constructed and screened four single-chain variable fragment (scFv) libraries—two synthetic and two immunized—against hA2AR and antagonist-stabilized hA2AR. After biopanning and ELISA screening, scFv hits were reformatted to human IgG and triaged in a series of cellular binding and functional assays to identify a lead candidate. Lead candidate TB206-001 displayed nanomolar binding of hA2AR-overexpressing HEK293 cells; cross-reactivity with mouse and cynomolgus A2AR but not human A1, A2B, or A3 receptors; functional antagonism of hA2AR in hA2AR-overexpressing HEK293 cells and peripheral blood mononuclear cells (PBMCs); and tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Given its therapeutic properties, TB206-001 is a good candidate for incorporation into next-generation bispecific immunotherapeutics. [ABSTRACT FROM AUTHOR]

The rapid spread of highly pathogenic avian influenza (HPAI) A (H5N1) viruses in Southeast Asia in 2004 prompted the New Zealand Ministry for Primary Industries to expand its avian influenza surveillance in wild birds. A total of 18,693 birds were sampled between 2004 and 2020, including migratory shorebirds (in 2004–2009), other coastal species (in 2009–2010), and resident waterfowl (in 2004–2020). No avian influenza viruses (AIVs) were isolated from cloacal or oropharyngeal samples from migratory shorebirds or resident coastal species. Two samples from red knots (Calidris canutus) tested positive by influenza A RT-qPCR, but virus could not be isolated and no further characterization could be undertaken. In contrast, 6179 samples from 15,740 mallards (Anas platyrhynchos) tested positive by influenza A RT-qPCR. Of these, 344 were positive for H5 and 51 for H7. All H5 and H7 viruses detected were of low pathogenicity confirmed by a lack of multiple basic amino acids at the hemagglutinin (HA) cleavage site. Twenty H5 viruses (six different neuraminidase [NA] subtypes) and 10 H7 viruses (two different NA subtypes) were propagated and characterized genetically. From H5- or H7-negative samples that tested positive by influenza A RT-qPCR, 326 AIVs were isolated, representing 41 HA/NA combinations. The most frequently isolated subtypes were H4N6, H3N8, H3N2, and H10N3. Multivariable logistic regression analysis of the relations between the location and year of sampling, and presence of AIV in individual waterfowl showed that the AIV risk at a given location varied from year to year. The H5 and H7 isolates both formed monophyletic HA groups. The H5 viruses were most closely related to North American lineages, whereas the H7 viruses formed a sister cluster relationship with wild bird viruses of the Eurasian and Australian lineages. Bayesian analysis indicates that the H5 and H7 viruses have circulated in resident mallards in New Zealand for some time. Correspondingly, we found limited evidence of influenza viruses in the major migratory bird populations visiting New Zealand. Findings suggest a low probability of introduction of HPAI viruses via long-distance bird migration and a unique epidemiology of AIV in New Zealand. [ABSTRACT FROM AUTHOR]

The functional impact of intratumoral heterogeneity has been difficult to assess in the absence of a means to interrogate dynamic, live-cell biochemical events in the native tissue context of a human tumor. Conventional histological methods can reveal morphology and static biomarker expression patterns but do not provide a means to probe and evaluate tumor functional behavior and live-cell responsiveness to experimentally controlled stimuli. Here, we describe an approach that couples vibratome-mediated viable tissue sectioning with live-cell confocal microscopy imaging to visualize human parathyroid adenoma tumor cell responsiveness to extracellular calcium challenge. Tumor sections prepared as 300 micron-thick tissue slices retain viability throughout a >24 hour observation period and retain the native architecture of the parental tumor. Live-cell observation of biochemical signaling in response to extracellular calcium challenge in the intact tissue slices reveals discrete, heterogeneous kinetic waveform categories of calcium agonist reactivity within each tumor. Plotting the proportion of maximally responsive tumor cells as a function of calcium concentration yields a sigmoid dose-response curve with a calculated calcium EC50 value significantly elevated above published reference values for wild-type calcium-sensing receptor (CASR) sensitivity. Subsequent fixation and immunofluorescence analysis of the functionally evaluated tissue specimens allows alignment and mapping of the physical characteristics of individual cells within the tumor to specific calcium response behaviors. Evaluation of the relative abundance of intracellular PTH in tissue slices challenged with variable calcium concentrations demonstrates that production of the hormone can be dynamically manipulated ex vivo. The capability of visualizing live human tumor tissue behavior in response to experimentally controlled conditions opens a wide range of possibilities for personalized ex vivo therapeutic testing. This highly adaptable system provides a unique platform for live-cell ex vivo provocative testing of human tumor responsiveness to a range of physiological agonists or candidate therapeutic compounds.

The children of older fathers have increased risks of developing schizophrenia spectrum disorders, and among those who develop these disorders, those with older fathers present with more severe clinical symptoms. However, the influence of advanced paternal age on other important domains related to schizophrenia, such as quantitative endophenotype deficit levels, remains unknown. This study investigated the associations between paternal age and level of endophenotypic impairment in a well-characterized family-based sample from the Consortium on the Genetics of Schizophrenia (COGS). All families included at least one affected subject and one unaffected sibling. Subjects met criteria for schizophrenia (probands; n = 293) or were unaffected first-degree siblings of those probands (n = 382). Paternal age at the time of subjects birth was documented. Subjects completed a comprehensive clinical assessment and a battery of tests that measured 16 endophenotypes. After controlling for covariates, potential paternal age-endophenotype associations were analyzed using one model that included probands alone and a second model that included both probands and unaffected siblings. Endophenotype deficits in the Identical Pairs version of the 4-digit Continuous Performance Test and in the Penn Computerized Neurocognitive Battery verbal memory test showed significant associations with paternal age. However, after correcting for multiple comparisons, no endophenotype was significantly associated with paternal age. These findings suggest that factors other than advanced paternal age at birth may account for endophenotypic deficit levels in schizophrenia.

This study tested the usability of a home-based self-administration transcranial direct current stimulation (tDCS) device designed specifically for women's health needs. This is a single center triple blinded clinical usability study for a new wireless, Bluetooth-controlled wearable tDCS device for women's health. The study aims to evaluate the usability and effective blinding of a home-based tDCS system. A total of forty-nine women of reproductive age were randomly allocated (1:1) to receive one session of active tDCS (n = 24) or sham tDCS (n = 25) over the motor and dorsolateral prefrontal cortex. Each participant self-administered one 20-minute session without supervision following guidance on a software application alone. The System Usability Scale (SUS) and the Patient Global Impression of Change (PGIC) were used to evaluate the usability of the system. Regardless of sham or active conditions, all users found the system easy to use without the support of researchers. Usability scores were considered to be "excellent" in both groups and no significant difference was found between sham and active groups showing effective blinding of the device (Active group: 93.7 (83.1–97.5); Sham group 90 (86.2–95) p = 0.79) and PGIC (Active group: 2 (1–2.75); Sham group 2 (1–2) p = 0.99) using an unpaired t-test or non-parametric statistical tests accordingly. The new Bluetooth-controlled wearable tDCS device is easy, safe to use and completely controlled by a smartphone app. This device is focused on women's health and will be tested as an alternative treatment for chronic pelvic pain and mood disturbance associated with menstrual cycles in further research. [ABSTRACT FROM AUTHOR]

Introduction: Despite the scale-up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at 6 weeks, 6, and and 24 months postpartum among pregnant women living with HIV and initiating Option B+. Women were randomized to a peer group support, community-based drug distribution and income-generating intervention called "Friends for Life Circles" (FLCs) versus the standard of care (SOC). Our secondary outcome was infant HIV status and HIV-free survival at 6 weeks and 18 months postpartum. Methods: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study at any gestational age. Participants were randomized 1:1 to the unblinded FLC intervention or SOC at enrolment and assessed for adherence to the prevention of mother-to-child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12, and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum and supported by plasma HIV-1 RNA viral load (VL) measured at the same time points, retention in care through the end of study, and HIV status and HIV-free survival of infants at 18 months postpartum. The FLC groups were formed during pregnancy within 4 months of enrollment and held monthly meetings in their communites, and were followed up until the last group participant reached 24 months post delivery. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. Results: There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p = 0.022. The adjusted HR of visit dropout was 2.4 times greater among participants randomized to SOC compared to FLC (aHR = 2.363, 95% CI: 1.199–4.656, p = 0.013). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6, and 24 months postpartum. Eight of the 431 infants tested at 18 months were HIV positive (1.9%), however, this was not statistically different among mothers enrolled in the FLC arm compared to those in the SOC arm. At 18 months, HIV-free survival of children born to mothers in the FLC arm was significantly higher than that of children born to mothers in the SOC arm. Conclusions: Our findings suggest that programmatic interventions that provide group support, community-based ART distribution, and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and ultimately, to the elimination of mother-to-child HIV transmission (EMTCT). Trial registration: NCT02515370 (04/08/2015) on ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Fungi are among key actors in the biogeochemical processes occurring in mangrove ecosystems. In this study, we investigated the changes of fungal communities in selected mangrove species by exploring differences in diversity, structure and the degree of ecological rearrangement occurring within the rhizospheres of four mangrove species (Sonneratia alba, Rhizophora mucronata, Ceriops tagal and Avicennia marina) at Gazi Bay and Mida Creek in Kenya. Alpha diversity investigation revealed that there were no significant differences in species diversity between the same mangrove species in the different sites. Rather, significant differences were observed in fungal richness for some of the mangrove species. Chemical parameters of the mangrove sediment significantly correlated with fungal alpha diversity and inversely with richness. The fungal community structure was significantly differentiated by mangrove species, geographical location and chemical parameters. Taxonomic analysis revealed that 96% of the amplicon sequence variants belonged to the Phylum Ascomycota, followed by Basidiomycota (3%). Predictive FUNGuild and co-occurrence network analysis revealed that the fungal communities in Gazi Bay were metabolically more diverse compared to those of Mida Creek. Overall, our results demonstrate that anthropogenic activities influenced fungal richness, community assembly and their potential ecological functions in the mangrove ecosystems investigated. [ABSTRACT FROM AUTHOR]