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This study aimed to characterise three Ghanaian local chicken ecotypes, namely, Interior Savannah, Forest, and Coastal Savannah, based on morphological data and single nucleotide polymorphism (SNP) genotypes. Morphological data including body weight, shank length, body girth, back length, thigh length, beak length, comb length, and wattle length were collected from 250 local chickens. DNA isolated from blood of 1,440 local chickens was used for SNP genotyping with the Affymetrix chicken 600k SNP chip. Principal component analysis showed that Forest and Coastal Savannah birds were closely related. Generally, all three ecotypes exhibited high genetic diversity, especially birds from the Interior Savannah zone. Morphological characterisation showed that ecotype (p = 0.016) and sex (p = 0.000) had significant effects on body weight. Birds of the Interior Savannah ecotype were the heaviest (p = 0.004), with mean weights of 1.23 kg for females and 1.40 kg for males. Sex also had a strong significant effect on most of the morphological measurements, but the sex * ecotype interaction effect was not significant. Very few of the feather phenotypes previously reported to be associated with heat resistance-frizzle (2%) and naked neck (1.6%)-were found in the studied populations. It is concluded that the three local ecotypes are genetically diverse but with similar morphological features and the information provided would be useful for future selection decisions.

In various organisms, sequencing of selectively bred lines at apparent selection limits has demonstrated that genetic variation can remain at many loci, implying that evolution at the genetic level may continue even if the population mean phenotype remains constant. We compared selection signatures at generations 22 and 61 of the High Runner mouse experiment, which includes 4 replicate lines bred for voluntary wheel-running behavior (HR) and 4 non-selected control (C) lines. Previously, we reported multiple regions of differentiation between the HR and C lines, based on whole-genome sequence data for 10 mice from each line at generation 61, which was >31 generations after selection limits had been reached in all HR lines. Here, we analyzed pooled sequencing data from ~20 mice for each of the 8 lines at generation 22, around when HR lines were reaching limits. Differentiation analyses of allele frequencies at ~4.4 million SNP loci used the regularized T-test and detected 258 differentiated regions with FDR = 0.01. Comparable analyses involving pooling generation 61 individual mouse genotypes into allele frequencies by line produced only 11 such regions, with almost no overlap among the largest and most statistically significant peaks between the two generations. These results implicate a sort of genetic churn that continues at loci relevant for running. Simulations indicate that loss of statistical power due to random genetic drift and sampling error are insufficient to explain the differences in selection signatures. The 13 differentiated regions at generation 22 with strict culling measures include 79 genes related to a wide variety of functions. Gene ontology identified pathways related to olfaction and vomeronasal pathways as being overrepresented, consistent with generation 61 analyses, despite those specific regions differing between generations. Genes Dspp and Rbm24 are also identified as potentially explaining known bone and skeletal muscle differences, respectively, between the linetypes.

El Gigante rockshelter in western Honduras provides a deeply stratified archaeological record of human-environment interaction spanning the entirety of the Holocene. Botanical materials are remarkably well preserved and include important tree (e.g., ciruela (Spondias), avocado (Persea americana)) and field (maize (Zea mays), beans (Phaseolus), and squash (Cucurbita)) crops. Here we provide a major update to the chronology of tree and field crop use evident in the sequence. We report 375 radiocarbon dates, a majority of which are for short-lived botanical macrofossils (e.g., maize cobs, avocado seeds, or rinds). Radiocarbon dates were used in combination with stratigraphic details to establish a Bayesian chronology for ~9,800 identified botanical samples spanning the last 11,000 years. We estimate that at least 16 discrete intervals of use occurred during this time, separated by gaps of ~100-2,000 years. The longest hiatus in rockshelter occupation was between ~6,400 and 4,400 years ago and the deposition of botanical remains peaked at ~2,000 calendar years before present (cal BP). Tree fruits and squash appeared early in the occupational sequence (~11,000 cal BP) with most other field crops appearing later in time (e.g., maize at ~4,400 cal BP; beans at ~2,200 cal BP). The early focus on tree fruits and squash is consistent with early coevolutionary partnering with humans as seed dispersers in the wake of megafaunal extinction in Mesoamerica. Tree crops predominated through much of the Holocene, and there was an overall shift to field crops after 4,000 cal BP that was largely driven by increased reliance on maize farming.

BackgroundComplex systems models of breast cancer have previously focused on prediction of prognosis and clinical events for individual women. There is a need for understanding breast cancer at the population level for public health decision-making, for identifying gaps in epidemiologic knowledge and for the education of the public as to the complexity of this most common of cancers.Methods and findingsWe developed an agent-based model of breast cancer for the women of the state of California using data from the U.S. Census, the California Health Interview Survey, the California Cancer Registry, the National Health and Nutrition Examination Survey and the literature. The model was implemented in the Julia programming language and R computing environment. The Paradigm II model development followed a transdisciplinary process with expertise from multiple relevant disciplinary experts from genetics to epidemiology and sociology with the goal of exploring both upstream determinants at the population level and pathophysiologic etiologic factors at the biologic level. The resulting model reproduces in a reasonable manner the overall age-specific incidence curve for the years 2008-2012 and incidence and relative risks due to specific risk factors such as BRCA1, polygenic risk, alcohol consumption, hormone therapy, breastfeeding, oral contraceptive use and scenarios for environmental toxin exposures.ConclusionsThe Paradigm II model illustrates the role of multiple etiologic factors in breast cancer from domains of biology, behavior and the environment. The value of the model is in providing a virtual laboratory to evaluate a wide range of potential interventions into the social, environmental and behavioral determinants of breast cancer at the population level.

BackgroundEpidemiological studies of interstitial lung disease (ILD) are limited by small numbers and tertiary care bias. Investigators have leveraged the widespread use of electronic health records (EHRs) to overcome these limitations, but struggle to extract patient-level, longitudinal clinical data needed to address many important research questions. We hypothesized that we could automate longitudinal ILD cohort development using the EHR of a large, community-based healthcare system.Study design and methodsWe applied a previously validated algorithm to the EHR of a community-based healthcare system to identify ILD cases between 2012-2020. We then extracted disease-specific characteristics and outcomes using fully automated data-extraction algorithms and natural language processing of selected free-text.ResultsWe identified a community cohort of 5,399 ILD patients (prevalence = 118 per 100,000). Pulmonary function tests (71%) and serologies (54%) were commonly used in the diagnostic evaluation, whereas lung biopsy was rare (5%). IPF was the most common ILD diagnosis (n = 972, 18%). Prednisone was the most commonly prescribed medication (911, 17%). Nintedanib and pirfenidone were rarely prescribed (n = 305, 5%). ILD patients were high-utilizers of inpatient (40%/year hospitalized) and outpatient care (80%/year with pulmonary visit), with sustained utilization throughout the post-diagnosis study period.DiscussionWe demonstrated the feasibility of robustly characterizing a variety of patient-level utilization and health services outcomes in a community-based EHR cohort. This represents a substantial methodological improvement by alleviating traditional constraints on the accuracy and clinical resolution of such ILD cohorts; we believe this approach will make community-based ILD research more efficient, effective, and scalable.

BackgroundTanzania has made significant progress in improving access to HIV care and treatment. However, virologic suppression among people living with HIV (PLHIV) has not been fully realized. In March 2019, Tanzania introduced a World Health Organization (WHO)-recommended dolutegravir-based regimen as the default first-line regimen. Eighteen months later we investigated the HIV viral suppression rates and the factors associated with lack of viral suppression among PLHIV (children and adults) in Tanzania.MethodologyA cross-sectional survey was conducted from September to December 2020 among PLHIV on antiretroviral therapy (ART) in Tanzania. Whole blood samples, demographic data and clinical information were obtained from eligible adults (≥15 years) and children (< 15 years) attending thirty-six HIV care and treatment centres located in 22 regions of Tanzania mainland. A whole blood sample from each participant was processed into plasma and HIV viral load was estimated using real-time PCR. HIV viral suppression was defined at a cut-off of < 50 copies/mL as recommended by WHO. Analyses were conducted using descriptive statistics to establish the national representative prevalence of viral suppression, and logistic regression analyses to determine independent factors associated with non-suppression.ResultsA total of 2,039 PLHIV on ART were recruited; of these, adults and children were 57.5% (n = 1173) and 42.5% (n = 866), respectively. Among the adult population, the mean age and standard deviation (SD) was 42.1 ± 12.4 years, with 64.7% being female. Among children, the mean age and SD were 9.6 ± 3 years, and 53.2% were female. Overall viral suppression at < 50 copies/mL (undetectable) was achieved in 87.8% of adults and 74.4% of children. Adults and children on dolutegravir-based regimen recorded viral suppression rates of 89.7% and 85.1% respectively. Factors independently associated with lack of viral suppression status in the adult population were age and ART adherence while in the children population, the factors were sex, ART adherence, and current ART regimen (pConclusionDolutegravir-based regimens are promising to help attain epidemic control in Tanzania. More efforts especially on ART adherence are needed to attain optimal treatment outcomes for children and adults PLHIV in Tanzania.

Estimating the densities of marine prey observed in animal-borne video loggers when encountered by foraging predators represents an important challenge for understanding predator-prey interactions in the marine environment. We used video images collected during the foraging trip of one chinstrap penguin (Pygoscelis antarcticus) from Cape Shirreff, Livingston Island, Antarctica to develop a novel approach for estimating the density of Antarctic krill (Euphausia superba) encountered during foraging activities. Using the open-source Video and Image Analytics for a Marine Environment (VIAME), we trained a neural network model to identify video frames containing krill. Our image classifier has an overall accuracy of 73%, with a positive predictive value of 83% for prediction of frames containing krill. We then developed a method to estimate the volume of water imaged, thus the density (N·m-3) of krill, in the 2-dimensional images. The method is based on the maximum range from the camera where krill remain visibly resolvable and assumes that mean krill length is known, and that the distribution of orientation angles of krill is uniform. From 1,932 images identified as containing krill, we manually identified a subset of 124 images from across the video record that contained resolvable and unresolvable krill necessary to estimate the resolvable range and imaged volume for the video sensor. Krill swarm density encountered by the penguins ranged from 2 to 307 krill·m-3 and mean density of krill was 48 krill·m-3 (sd = 61 krill·m-3). Mean krill biomass density was 25 g·m-3. Our frame-level image classifier model and krill density estimation method provide a new approach to efficiently process video-logger data and estimate krill density from 2D imagery, providing key information on prey aggregations that may affect predator foraging performance. The approach should be directly applicable to other marine predators feeding on aggregations of prey.

Unhealthy diet is associated with increased risk of cardiovascular diseases (CVD). However, there are no studies reporting the impact and trends of dietary risk factors on CVD in Australia. This study aimed to determine the burden of CVDs attributable to dietary risk factors in Australia between 1990 and 2019. We used data from the Global Burden of Diseases (GBD) study and quantified the rate (per 100,000) of deaths, disability-adjusted life years (DALYs), years lived with a disability (YLDs), and years of life lost (YLLs) for 21 CVDs attributable to 13 dietary risk factors (eight food groups and five nutrients) in Australia by sex and age groups (≥25 years and over). In 2019, the age-standardised rates of deaths, YLDs, YLLs, and DALYs attributable to dietary risk factors attributable to CVDs in the Australian population were 26.5, 60.8, 349.9, and 410.8 per 100,000 in women and 46.1, 62.6, 807.0, and 869.6 in men. Between 1990 and 2019, YLLs consistently contributed more towards the rates of DALYs than YLDs. Over the 30-year period, CVD deaths, YLLs, and DALYs attributable to dietary risk factors declined in both women and men. The leading dietary risk factors for CVD deaths and DALYs were a diet high in red meat (6.1 deaths per 100,000 [3.6, 8.7] and 115.6 DALYs per 100,000 [79.7, 151.6]) in women and a diet low in wholegrains (11.3 deaths [4.4, 15.1] and 220.3 DALYs [86.4, 291.8]) in men. Sex differences were observed in the contribution of dietary risk factors to CVD over time such that the lowest rate of decrease in deaths and DALYs occurred with diets high in sodium in women and diets high in processed meat in men. Although the burden of diet-related CVD has decreased significantly in the Australian population over the past 30 years, diets low in wholegrains and high in red meat continue to contribute significantly to the overall CVD burden. Future nutrition programs and policies should target these dietary risk factors.

Post-contact immobility (PCI) is a final attempt to avoid predation. Here, for the first time, we examine the pattern of movement and immobility when antlion larvae resume activity after PCI. To simulate contact with, and escape from, a predator we dropped the larvae onto three different substrates: Paper, Shallow sand (2.3mm-deep) and Deep sand (4.6mm-deep). The Paper lining a Petri dish represented a hard surface that antlion larvae could not penetrate to hide. The Shallow sand permitted the antlions to dig but not to submerge completely whereas the Deep sand allowed them both to dig and to submerge. We tracked their paths automatically and recorded alternating immobility and movement durations over 90min. On the impenetrable substrate, antlion larvae showed super-diffusive dispersal, their movement durations became longer, their immobility durations became shorter and their instantaneous speeds increased. This is consistent with the antlions needing to leave an area of hard substrate and quickly to find somewhere to hide. On Shallow sand, antlion larvae exhibited a modest increase in movement duration, a modest decrease in immobility duration and a concomitant diffusive dispersal. This is consistent with their use of a spiral search, presumably for a suitable depth of sand, to conceal themselves. On Deep sand, the movement and immobility durations of the antlion larvae did not change and their dispersal was sub-diffusive because they were able to bury themselves. On Paper, the distribution of immobility durations had a long tail, consistent with a log-normal distribution. On Shallow and Deep sand, most of the distribution was fitted better by a power law or a log-normal. Our results suggest that PCI in antlion larvae is a disruptive event and that post-PCI movement and immobility gradually return to the pattern typical of intermittent locomotion, depending on the scope for burying and hiding in the substrate.

Pre-exposure prophylaxis (PrEP) is being scaled up to prevent HIV acquisition among adolescent girls and young women (AGYW) in Eastern and Southern Africa. In a prior study more than one-third of AGYW 'mystery shoppers' stated they would not return to care based on interactions with health providers. We examined the experiences of AGYW in this study to identify main barriers to effective PrEP services. Unannounced patient actors (USP/'mystery shoppers') posed as AGYWs seeking PrEP using standardized scenarios 8 months after providers had received training to improve PrEP services. We conducted targeted debriefings using open-ended questions to assess PrEP service provision and counseling quality with USPs immediately following their visit. Debriefings were audio-recorded and transcribed. Transcripts were analyzed using thematic analysis to explore why USPs reported either positive or negative encounters. We conducted 91 USP debriefings at 24 facilities and identified three primary influences on PrEP service experiences: 1) Privacy improved likelihood of continuing care, 2) respectful attitudes created a safe environment for USPs, and 3) patient-centered communication improved the experience and increased confidence for PrEP initiation among USPs. Privacy and provider attitudes were primary drivers that influenced decision-making around PrEP in USP debriefs. Access to privacy and improving provider attitudes is important for scale-up of PrEP to AGYW.

Among adolescents, HIV/AIDs remains a significant cause of death globally [1-4]. Given the unique stages in human development, adolescents have been shown to fall within a sexually active phase. Combined with other social and structural factors in their immediate environments, HIV prevention and care among adolescents can be filled with challenges for intervention. This paper outlines this protocol to systematically review peer-reviewed literature in prevention and care among adolescents 10-19 years. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) will be used to report this scoping review. The review will involve screening and extracting data using covidence as the primary tool. The review will encompass quantitative, qualitative, and mixed methods studies, utilizing a search strategy from electronic databases such as PubMed (NCBI), Web of Science Core Collection (Clarivate), Embase (Elsevier), and Scopus (Elsevier). Additionally, a search will be conducted for grey literature using Global Index Medicus (WHO), MedNar (Deep Web Technologies), and Central Register of Controlled Trials (Cochrane). Duplicate removal and selection of articles that meet the inclusion criteria for the study will be performed using Covidence. Once the screening process is complete, data will be extracted from the full-text screened articles in Covidence. We will pilot the extracted data in Covidence to ensure that all relevant information has been captured, making necessary changes if required. Data extraction will be carried out by at least two authors, with any conflicts resolved by the same authors. If a conflict cannot be resolved between the two, a third author will make a final determination. We aim to analyze data thematically by employing a grounded theory approach to generate codes pertinent to the research question. The team will review and discuss codes to create a cohesive set of codes that will be instrumental in identifying knowledge gaps and constructing themes that summarize the data. The proposed systematic review will be among the pioneering efforts to rigorously assess global data on HIV prevention and care, with a specific focus on adolescents 10-19 years. It will consider the diverse socio-economic factors and experiences shaping these adolescents' lives in HIV prevention and care. We expect this review to yield critical insights into the present landscape of HIV prevention and care for individuals aged 10-19. These findings will also play a pivotal role in shaping the development of a global framework that researchers and stakeholders can readily adopt and implement across socio-economic contexts. This framework will aim to address the unique needs of all adolescents concerning HIV prevention and care.

Initial transmission of severe acute respiratory syndrome virus-2 (SARS-CoV-2) was highest in densely populated regions of Kenya. Transmission gradually trickled down to the less densely populated, remote and underserved regions such as the pastoral regions of Kajiado County which are characterized by poor healthcare systems. Molecular assays that were pivotal for COVID-19 diagnosis were not available in these regions. Serology is an alternative method for retrospectively tracking the transmission of SARS-CoV-2 in such populations. Dry blood spots (DBS) were prepared from consenting patients attending six health facilities in Kajiado County from March 2020 to March 2022. Upon elution, we conducted an enzyme-linked immunosorbent assay (ELISA) for the detection of SARS-Cov-2 IgG antibodies. Of the 908 DBSs we analyzed, 706 (78%) were from female participants. The overall seropositivity to SARS-Cov-2 antibodies was 7.3% (95% CI 5.7-9.1). The elderly (over 60 years) and male participants had a high likelihood of testing positive for SAR-CoV-2 infections. Mashuru (15.6%, 14/90) and Meto (15%, 19/127) health facilities registered the highest proportion of seropositive participants. Evidence of SARS-CoV-2 transmission among pastoralists in the remote and underserved regions of Kajiado County was established by DBS sampling and serologic testing.

On the 11th of March 2020, the world faced a new global pandemic, COVID-19 which is a disease caused by the novel coronavirus, it had multiple devastating outcomes on multiple sectors along with significant rates of mortality. These challenges encouraged the development of multiple testing methods, as well as anti-viral medications such as Molnupiravir, as well as evaluating the efficacy of available medications against it, like; Azithromycin, Ritonavir and Hydroxychloroquine. Vaccination against COVID-19 forged into a significant challenge, few months ensuing the first case of SARS-CoV-2, which was diagnosed in December 2019, in Wuhan-China, thus, multiple vaccines were approved for use around the world to combat this pandemic. Our study includes a sample of 556 oncology patients at Augusta Victoria Hospital in Jerusalem, all patients were tested using Panbio rapid antigen test and Allplex PCR Assay. The main objective was to study the sensitivity and specificity of Rapid antigen test, which contributes to a faster isolation call and management of infected patients, thus decreasing the risk on spread to other patients and health care. Patients were categorized based on two factors: Ct range and age group and studying their possible effect on false-negative results. Patients with Ct value less than 20, had the highest detection rate which is consistent with other studies in the literature. The sensitivity and specificity of Panbio Rapid Antigen testing were of 69.9% and 100%, respectively. A correlation between age group and false negative results could not be made, but a correlation between Ct value and false negative result was noticed, Ct value was directly related to false negative results. P-value of 0.007 indicated that results were statistically significant where PCR test is considered more sensitive compared to rapid antigen test.

In various organisms, sequencing of selectively bred lines at apparent selection limits has demonstrated that genetic variation can remain at many loci, implying that evolution at the genetic level may continue even if the population mean phenotype remains constant. We compared selection signatures at generations 22 and 61 of the "High Runner" mouse experiment, which includes 4 replicate lines bred for voluntary wheel-running behavior (HR) and 4 non-selected control (C) lines. Previously, we reported multiple regions of differentiation between the HR and C lines, based on whole-genome sequence data for 10 mice from each line at generation 61, which was >31 generations after selection limits had been reached in all HR lines. Here, we analyzed pooled sequencing data from ~20 mice for each of the 8 lines at generation 22, around when HR lines were reaching limits. Differentiation analyses of allele frequencies at ~4.4 million SNP loci used the regularized T-test and detected 258 differentiated regions with FDR = 0.01. Comparable analyses involving pooling generation 61 individual mouse genotypes into allele frequencies by line produced only 11 such regions, with almost no overlap among the largest and most statistically significant peaks between the two generations. These results implicate a sort of "genetic churn" that continues at loci relevant for running. Simulations indicate that loss of statistical power due to random genetic drift and sampling error are insufficient to explain the differences in selection signatures. The 13 differentiated regions at generation 22 with strict culling measures include 79 genes related to a wide variety of functions. Gene ontology identified pathways related to olfaction and vomeronasal pathways as being overrepresented, consistent with generation 61 analyses, despite those specific regions differing between generations. Genes Dspp and Rbm24 are also identified as potentially explaining known bone and skeletal muscle differences, respectively, between the linetypes.

Effective control requires knowledge of the process dynamics to guide the system toward desired states. In many control applications this knowledge is expressed mathematically or through data-driven models, however, as complexity grows obtaining a satisfactory mathematical representation is increasingly difficult. Further, many data-driven approaches consist of abstract internal representations that may have no obvious connection to the underlying dynamics and control, or, require extensive model design and training. Here, we remove these constraints by demonstrating model predictive control from generalized state space embedding of the process dynamics providing a data-driven, explainable method for control of nonlinear, complex systems. Generalized embedding and model predictive control are demonstrated on nonlinear dynamics generated by an agent based model of 1200 interacting agents. The method is generally applicable to any type of controller and dynamic system representable in a state space.

IntroductionUnderstanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia.MethodsWe performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures.ResultsData from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, pConclusionIn men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

Transrectal ultrasonography is known as the gold standard for pregnancy detection, but requires costly equipment and technical skills; therefore, access to an inexpensive and more user-friendly method with similar accuracy could benefit cattle producers. Detection of pregnancy-associated glycoproteins can accurately determine pregnancy in ruminants; however, usually requires specialized equipment for the assay. Thus, the objectives of these studies were to 1) validate the IDEXX Alertys OnFarm Pregnancy Test (lateral flow) and compare the accuracy of all three commercial PAG assays to transrectal ultrasonography and 2) to determine the postpartum interval necessary for clearance of pregnancy-associated glycoproteins from the previous pregnancy to avoid false positives. In study 1, blood samples from previously identified pregnant Bos taurus females from six different herds (nulliparous n = 1,205 and multiparous n = 1,539; samples collected between d 27 to 285 of gestation over a three-year period) were utilized. In study 2, postpartum females (primiparous n = 48 and multiparous n = 66) from one herd were utilized: (n = 1,066; samples collected weekly for up to 12 weeks postpartum). In study 1, level of agreement between different methods of pregnancy detection was determined by Pearson's correlation and Kappa scores. In study 2, data were analyzed as a repeated measure using the MIXED procedure of SAS with main effects of parity, days postpartum (dpp), and parity by days postpartum, then data were analyzed further using the REG procedure of SAS. In study 1, transrectal ultrasonography and lateral flow were positively correlated (r = 0.77; P

A patient with a neuroendocrine tumor and history of coronary artery disease underwent PET with 68Ga-DOTATATE PET tracer for tumor visualization. Analysis of the scan showed uptake of 68Ga-DOTATATE in the left ventricle corresponding to previous myocardial infarct. 68Ga-DOTATATE binds by somatostatin receptors (SSTR) and it has been proposed that it may be useful for the detection of cardiac inflammatory lesions. We aimed to test whether SSTR could be upregulated in cardiac fibrotic scar. We analyzed SSTR in cardiac samples from patients with end-stage ischemic cardiomyopathy (ICM, n = 8) and control hearts (n = 5). In mature ICM tissue, SSTR1 and SSTR2 expression was unchanged and SSTR5 expression was significantly decreased in ICM samples vs. control. Immunohistochemistry showed increased SSTR1 and SSTR2 in ICM. Areas with SSTR1 or SSTR2 staining were often adjacent to fibrotic areas. The majority of SSTR1 and SSTR2 staining localized in cardiomyocytes in fibrotic scar-rich areas where CD68 macrophage staining was not present. SSTR are occasionally upregulated in cardiac fibrotic areas. When using 68Ga-DOTATATE PET tracer to detect cardiac sarcoidosis or atherosclerotic plaque, the possibility of tracer uptake in fibrotic areas should be considered.

[This corrects the article DOI: 10.1371/journal.pone.0272558.].

BackgroundInfectious disease-related stigma is a pervasive global issue that impedes disease control efforts by increasing reluctance to seek treatment or engagement in prevention behaviors for fear of ostracism. Despite this, there is limited research on COVID-19 stigma in Africa, specifically rural South Africa, which has faced infectious disease-related stigma throughout the HIV epidemic.MethodsPopulation-based surveys were conducted among 1,662 adults living in the Agincourt Health and Socio-Demographic Surveillance System (AHDSS) area in Mpumalanga, South Africa, in August-October 2020 and August-October 2021. Surveys measured anticipated COVID-19-related stigma from low to high levels. Changes in stigma between surveys were compared using Wilcoxon ranked sign tests, and log-binomial models estimated the association between socio-demographic factors and anticipated stigma at both intervals. Qualitative interviews were conducted in 2022 among 31 adults who completed the original surveys, and the data were analyzed thematically to describe anticipated, perceived, and enacted stigma.ResultsAnticipated stigma significantly decreased from the first to the second survey (p-value:ConclusionWhile COVID-19 stigma decreased over time in rural South Africa, different forms of stigma persisted and influenced participants' willingness to reveal their COVID-19 infection status. Given South Africa's history with infectious disease-related stigma hindering public health efforts, it is crucial that government bodies prioritize strategies to mitigate stigma in rural communities.

Individuals with clinical high risk (CHR) for psychosis experience significant distress, impaired general functioning and a high lifetime risk of self-harm and attempted suicide. The CHR period is an important phase in an individual's mental health where appropriate interventions may reduce the risk of progression to several negative outcomes, including the development of schizophrenia. Given that up to 80% of individuals with CHR have another diagnosable mental illness and almost half experience poor psychosocial functioning, developing interventions that address psychosocial functioning in young people with CHR is of great importance. This mixed-methods study aims to employ qualitative and quantitative methods to adapt an evidence-based comprehensive psychosocial and mental health self-efficacy program, the Optimal Health Program (OHP), and evaluate the feasibility, acceptability and preliminary clinical efficacy in young people with CHR. We aim to recruit 30 CHR participants (age 16-29 years) in a single-arm 12-week exploratory clinical trial. Feasibility metrics will include recruitment, retention, and data completion rates. Acceptability will be informed by the Client Satisfaction Questionnaire. Clinical assessments (psychosis spectrum symptoms, depression, and anxiety), functional measures, and cognitive outcomes will be completed at study entry and repeated post-intervention at 12-weeks. We will run pre-post test data analysis to examine changes following engagement in the OHP intervention. Qualitative interviews will be conducted post-intervention to further evaluate the acceptability of the intervention and the trial design, and will be analyzed using thematic analysis. OHP may enhance the long-term mental health, well-being and functioning of CHR youth. However, the intervention must first be adapted to a CHR population; then, the feasibility and preliminary efficacy of delivering an intervention tailored around the varied needs of the CHR group must be established before a larger-scale appropriately powered study is pursued. Trial registration: The trial is registered with ClinicalTrials.gov NCT05757128.

Selective serotonin re-uptake inhibitors (SSRI) widely used in the treatment of depression, anxiety, obsessive compulsive disorder, fibromyalgia, and migraine are among the most heavily prescribed drug class in the United States (US). Along with an overall rise in SSRI use, these medications are increasingly used by pregnant individuals and recent preclinical and clinical studies have indicated that SSRIs may increase the prevalence of congenital abnormalities and birth defects of the craniofacial region. Our group has developed pre-clinical models of study, including those that mimic the clinical use of SSRI in mice. Here we designed a study to interrogate a commonly prescribed SSRI drug, Citalopram, for its effects on craniofacial and dental development when introduced in utero. Pre-natal exposure to a clinically relevant dose of citalopram resulted in changes in craniofacial form identified by an increase in endocast volume in SSRI exposed postnatal day 15 mouse pups. More specifically, cranial length and synchondrosis length increased in SSRI exposed pups as compared to control pups of the same age. Additionally, growth center (synchondrosis) height and width and palate length and width decreased in SSRI exposed pups as compared to control un-exposed pups. Effects of SSRI on the molars was minimal. Craniofacial growth and development continue to be an area of interest in the investigation of in utero pharmaceutical drug exposure. Altogether these data indicate that prenatal SSRI exposure affects craniofacial form in multiple tissues and specifically at growth sites and centers of the skull.

BackgroundSpeculum lubrication may help to reduce the pain experienced during Pap-smear collection and hence increase uptake of cervical cancer screening and repeat testing, but there are fears of its interference with cytological results.AimTo determine and compare the adequacy of cervical cytology smears and the mean pain scores of women undergoing cervical cancer screening with or without speculum lubrication.MethodsThis was a randomised controlled study of 132 women having cervical cancer screening at a tertiary hospital in Nigeria. Sixty-six participants were randomly assigned to the 'Gel' and 'No Gel' groups, respectively. Pap smears were collected from each participant with a lubricated speculum ('Gel group') or a non-lubricated speculum ('No Gel group'). The primary outcome measures were the proportion of women with unsatisfactory cervical cytology smears and the mean numeric rating scale pain scores, while the secondary outcome measures were the proportion of women who were willing to come for repeat testing and the cytological diagnosis of Pap-smear results.ResultsThe baseline socio-demographic variables were similar in both groups. There was no significant difference in the proportion of unsatisfactory cervical smear results between the two groups (13.6% vs. 21.2%, p = 0.359). However, the mean pain scores were significantly lower in the gel group than in the no gel group (45.04 vs. 87.96; p 0.999) were willing to come for repeat cervical smears in the future.ConclusionSpeculum lubrication did not affect the adequacy of cervical smears but significantly reduced the pain experienced during pap smear collection. Also, it did not significantly affect the willingness to come for repeat cervical smears in the future.Trial registrationThe trial was registered with the Pan-African Clinical Trial Registry with a unique identification and registration number: PACTR2020077533364675.

BackgroundDespite the importance of labour market participation and the high number of people with disabilities in rural Africa who rely on subsistence agriculture to survive, very few studies have documented labour market outcomes among farmers with and without disabilities in Africa.ObjectiveWe examined how labour market participation differed by disability and other factors among smallholder farmers in Western Kenya.MethodsWe use cross-sectional data collected between January and April 2022 from sorghum farmers enrolled in a trial evaluating the impact of a programme designed to improve labour market participation among sorghum farmers in rural Western Kenya. Disability and Labour market outcomes were assessed using questions from the Washington Group /ILO Labor Force Survey Disability Module the ILO Labour Force Survey module respectively. Univariate and multiple regression analyses were conducted to identify socio-demographic characteristics and other related factors associated with labour market participation.ResultsAmong 4459 participants, disability was reported by 20.3% of women and 12.3% of men. Labour market participation was reported by 77.1% and 81.3% of women and men, respectively. Adjusting for demographic confounders, having a disability was associated with a lower likelihood of labour market participation (odds ratio 0.59, 95% confidence interval, 0.42-0.83, P = 0.001). These findings were similar in a modified model that looked at functional difficulties separately from anxiety and depression. Women, older participants, and those who were dependent on others were also more likely not to report participation in the labour market.ConclusionsIncreased recognition and understanding of functional limitations among smallholder farmers is vital for the success of economic empowerment programmes aimed at increasing labour market participation among the most vulnerable populations.

[This corrects the article DOI: 10.1371/journal.pone.0283604.].

Schistosomiasis is a neglected tropical disease which imposes a considerable and enduring impact on affected regions, leading to persistent morbidity, hindering child development, diminishing productivity, and imposing economic burdens. Due to the emergence of drug resistance and limited management options, there is need to develop additional effective inhibitors for schistosomiasis. In view of this, quantitative structure-activity relationship studies, molecular docking, molecular dynamics simulations, drug-likeness and pharmacokinetics predictions were applied to 39 Schistosoma mansoni Thioredoxin Glutathione Reductase (SmTGR) inhibitors. The chosen QSAR model demonstrated robust statistical parameters, including an R2 of 0.798, R2adj of 0.767, Q2cv of 0.681, LOF of 0.930, R2test of 0.776, and cR2p of 0.746, confirming its reliability. The most active derivative (compound 40) was identified as a lead candidate for the development of new potential non-covalent inhibitors through ligand-based design. Subsequently, 12 novel compounds (40a-40l) were designed with enhanced anti-schistosomiasis activity and binding affinity. Molecular docking studies revealed strong and stable interactions, including hydrogen bonding, between the designed compounds and the target receptor. Molecular dynamics simulations over 100 nanoseconds and MM-PBSA free binding energy (ΔGbind) calculations validated the stability of the two best-designed molecules. Furthermore, drug-likeness and pharmacokinetics prediction analyses affirmed the potential of these designed compounds, suggesting their promise as innovative agents for the treatment of schistosomiasis.

BackgroundDanish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women's outcomes after the first screening test at age 23.Methods and findingsOur study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9-5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3-59.3) women undergoing follow-up per detected CIN2+.ConclusionOverall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden.Trial registrationTrial registration number: NCT0304955.

BackgroundAntibiotic self-medication is one of the common causes of antibiotic resistance of bacterial organisms. The COVID-19 pandemic introduced a new paradigm shift and significantly influenced healthcare behaviors, including an increase in antibiotic self-medication, which contributes to antibiotic resistance. This study was aimed at determining the prevalence of antibiotic self-medication and the possible associated factors during the peak of the COVID-19 pandemic among adult residents of Tema in Ghana from April to July 2021.MethodsUsing a cross-sectional design, 400 adults were randomly selected and surveyed using a researcher-assisted questionnaire. Data were analyzed with IBM® SPSS® Statistics Version 22.0, considering associations significant at a 95% confidence interval (p < 0.05).ResultsOf the 400 respondents, (76%) 304 had practiced antibiotic self-medication within the previous 12 months during the COVID-19 pandemic. Significant factors associated with antibiotic self-medication included gender, age, marital status, education, occupation, and National Health Insurance Scheme subscription. Convenience and avoiding long hospital queues were primary non-medical reasons for antibiotic self-medication, while previous successful experience, easy access to antibiotics, treating symptoms, prophylaxis, and fear of hospital infection were the medical reasons for antibiotic self-medication. Commonly self-administered antibiotics were azithromycin (34%), amoxicillin/clavulanic acid (22%), and metronidazole (16%) for perceived respiratory tract and gastrointestinal tract infections.ConclusionsThe high prevalence of antibiotic self-medication observed during the COVID-19 pandemic underscores the need for enhanced public education and stricter enforcement of regulations governing antibiotic sales. The non-medical and medical factors of convenience, avoiding long hospital queues, previous successful experience, easy access to antibiotics, treating symptoms, prophylaxis, and fear of hospital infection which motivated antibiotic self-medication practices require the implementation of antimicrobial stewardship interventions.

IntroductionDue to the health consequences arising from climate change, medical students will inevitably interact with affected patients during their training and careers. Accordingly, medical schools must incorporate education on the impacts of climate change on health and equity into their curricula. We created a curricular thread called "Climate Change, Health, and Equity" in the first-year preclinical medical program to teach foundational concepts and foster self-reflection and critical consciousness.MethodsThe authors developed a continuum of practice including administrators, educators and faculty members, students, and community partners to plan and design curricular activities. First-year medical students at Duke University School of Medicine participated in seven mandatory foundational lectures and two experiential learning opportunities in the local community. Following completion of activities, students wrote a critical reflection essay and completed a self-directed learning exercise. Essays were evaluated using the REFLECT rubric to assess if students achieved critical reflection and for thematic analysis by Bloom's Taxonomy.ResultsAll students (118) submitted essays. A random sample of 30 (25%) essays underwent analysis. Evaluation by the REFLECT rubric underscored that all students were reflecting or critically reflecting on thread content. Thematic analysis highlighted that all students (30/30, 100%) were adept at identifying new areas of medical knowledge and connecting concepts to individual experiences, institutional practices, and public health and policy. Most students (27/30; 90%) used emotionally laden words, expressing negative feelings like frustration and fear but also positive sentiments of solidarity and hope regarding climate change and effects on health. Many students (24/30; 80%) expressed actionable items at every level including continuing self-directed learning and conversing with patients, minimizing healthcare waste, and advocating for climate-friendly policies.ConclusionAfter participating in the curricular thread, most medical students reflected on cognitive, affective, and actionable aspects relating to climate change, health, and equity.

ObjectiveTo understand the experiences of informal carers and the impact of role and activity changes on their health and wellbeing.MethodsA systematic search of CINHAL, MEDLINE, Embase, APA PsycInfo, and Web of Science was conducted. Studies were eligible if they included informal stroke carers (≥18 years), used a qualitative methodology, explored the roles and valued activities of stroke carers, and were published in English. The 10-item Critical Appraisal Skills Programme checklist for qualitative studies was used to assess methodological quality. The results of the included studies were thematically synthesised.ResultsA total of 36 qualitative studies were included and four overarching themes were identified: (1) Life adjustment; (2) Changing role and identity; (3) Changing activities: From meaningful to purposeful; and (4) Understanding and supporting carers.ConclusionThe sudden nature of stroke requires major readjustment in the carers life that has implications on their relationships, roles, and activities, subsequently impacting on their health and wellbeing. Health professionals and researchers should collaborate with stroke carers to identify their valued activities and implement realistic strategies to maintain these activities. Future interventions designed for carers should implement education about the importance of participating in valued activities and strategies to maintain these activities.

BackgroundThe rapid adoption of robotic surgical systems across Europe has led to a critical gap in training and credentialing for gastrointestinal (GI) surgeons. Currently, there is no existing standardised curriculum to guide robotic training, assessment and certification for GI trainees. This manuscript describes the protocol to achieve a pan-European consensus on the essential components of a comprehensive training programme for GI robotic surgery through a five-stage process.Methods and analysisIn Stage 1, a Steering Committee, consisting of international experts, trainees and educationalists, has been established to lead and coordinate the consensus development process. In Stage 2, a systematic review of existing multi-specialty robotic training curricula will be performed to inform the formulation of key position statements. In Stage 3, a comprehensive survey will be disseminated across Europe to capture the current state of robotic training and identify potential challenges and opportunities for improvement. In Stage 4, an international panel of GI surgeons, trainees, and robotic theatre staff will participate in a three-round Delphi process, seeking ≥ 70% agreement on crucial aspects of the training curriculum. Industry and patient representatives will be involved as external advisors throughout this process. In Stage 5, the robotic training curriculum for GI trainees will be finalised in a dedicated consensus meeting, culminating in the production of an Explanation and Elaboration (E&E) document.Registration detailsThe study protocol has been registered on the Open Science Framework (https://osf.io/br87d/).

Lithified layers of complex microbial mats known as microbialites are ubiquitous in the fossil record, and modern forms are increasingly identified globally. A key challenge to developing an understanding of microbialite formation and environmental role is how to investigate complex and diverse communities in situ. We selected living, layered microbialites (stromatolites) in a peritidal environment near Schoenmakerskop, Eastern Cape, South Africa to conduct a spatial survey mapping the composition and small molecule production of the microbial communities from environmental samples. Substrate core samples were collected from nine sampling stations ranging from the upper point of the freshwater inflow to the lower marine interface where tidal overtopping takes place. Substrate cores provided material for parallel analyses of microbial community diversity by 16S rRNA gene amplicon sequencing and metabolomics using LC-MS2. Species and metabolite diversities were correlated, and prominent specialized metabolites were targeted for preliminary characterization. A new series of cyclic hexadepsipeptides, named ibhayipeptolides, was most abundant in substrate cores of submerged microbialites. These results demonstrate the detection and identification of metabolites from mass-limited environmental samples and contribute knowledge about microbialite chemistry and biology, which facilitates future targeted studies of specialized metabolite function and biosynthesis.

BackgroundThe Pneumonia Score Index (PSI) was developed to estimate the risk of dying within 30 days of presentation for community-acquired pneumonia patients and is a strong predictor of 30-day mortality after COVID-19. However, three of its required 20 variables (skilled nursing home, altered mental status and pleural effusion) are not discreetly available in the electronic medical record (EMR), resulting in manual chart review for these 3 factors. The goal of this study is to compare a simplified 17-factor version (PSI-17) to the original (denoted PSI-20) in terms of prediction of 30-day mortality in COVID-19.MethodsIn this retrospective cohort study, the hospitalized patients with confirmed SARS-CoV-2 infection between 2/28/20-5/28/20 were identified to compare the predictive performance between PSI-17 and PSI-20. Correlation was assessed between PSI-17 and PSI-20, and logistic regressions were performed for 30-day mortality. The predictive abilities were compared by discrimination, calibration, and overall performance.ResultsBased on 1,138 COVID-19 patients, the correlation between PSI-17 and PSI-20 was 0.95. Univariate logistic regression showed that PSI-17 had performance similar to PSI-20, based on AUC, ICI and Brier Score. After adjusting for confounding variables by multivariable logistic regression, PSI-17 and PSI-20 had AUCs (95% CI) of 0.85 (0.83-0.88) and 0.86 (0.84-0.89), respectively, indicating no significant difference in AUC at significance level of 0.05.ConclusionPSI-17 and PSI-20 are equally effective predictors of 30-day mortality in terms of several performance metrics. PSI-17 can be obtained without the manual chart review, which allows for automated risk calculations within an EMR. PSI-17 can be easily obtained and may be a comparable alternative to PSI-20.

Older adults who are frail are likely to be sedentary. Prior interventions to reduce sedentary time in older adults have not been effective as there is little research about the context of sedentary behaviour (posture, location, purpose, social environment). Moreover, there is limited evidence on feasible measures to assess context of sedentary behaviour in older adults. The aim of our study was to determine the feasibility of measuring context of sedentary behaviour in older adults with pre-frailty or frailty using a combination of objective and self-report measures. We defined "feasibility process" using recruitment (20 participants within two-months), retention (85%), and refusal (20%) rates and "feasibility resource" if the measures capture context and can be linked (e.g., sitting-kitchen-eating-alone) and are all participants willing to use the measures. Context was assessed using a wearable sensor to assess posture, a smart home monitoring system for location, and an electronic or hard-copy diary for purpose and social context over three days in winter and spring. We approached 80 potential individuals, and 58 expressed interest; of the 58 individuals, 37 did not enroll due to lack of interest or medical mistrust (64% refusal). We recruited 21 older adults (72±7.3 years, 13 females, 13 frail) within two months and experienced two dropouts due to medical mistrust or worsening health (90% retention). The wearable sensor, indoor positioning system, and electronic diary accurately captured one domain of context, but the hard copy was often not completed with enough detail, so it was challenging to link it to the other devices. Although not all participants were willing to use the wearable sensor, indoor positioning system, or electronic diary, we were able to triage the measures of those who did. The use of wearable sensors and electronic diaries may be a feasible method to assess context of sedentary behaviour, but more research is needed with device-based measures in diverse groups.

Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that causes significant late morbidity and mortality following allogeneic hematopoietic cell transplantation. The "Close Assessment and Testing for Chronic GVHD (CATCH)" study is a multi-center Chronic GVHD Consortium prospective, longitudinal cohort study designed to enroll patients before hematopoietic cell transplantation and follow them closely to capture the development of chronic GVHD and to identify clinical and biologic biomarkers of chronic GVHD onset. Data are collected pre-transplant and every two months through one-year post-transplant with chart review thereafter. Evaluations include clinician assessment of chronic GVHD and its manifestations, patient-reported outcomes, multiple biospecimens (blood, saliva, tears, buccal mucosa and fecal samples, biopsies of skin and mouth), laboratory testing, and medical record abstraction. This report describes the rationale, design, and methods of the CATCH study, and invites collaboration with other investigators to leverage this resource. trial registration: This study is registered at www.clinicaltrials.gov as NCT04188912.

Camouflage is a widespread and well-studied anti-predator strategy, yet identifying which patterns provide optimal protection in any given scenario remains challenging. Besides the virtually limitless combinations of colours and patterns available to prey, selection for camouflage strategies will depend on complex interactions between prey appearance, background properties and predator traits, across repeated encounters between co-evolving predators and prey. Experiments in artificial evolution, pairing psychophysics detection tasks with genetic algorithms, offer a promising way to tackle this complexity, but sophisticated genetic algorithms have so far been restricted to screen-based experiments. Here, we present methods to test the evolution of colour patterns on physical prey items, under selection from wild predators in the field. Our techniques expand on a recently-developed open-access pattern generation and genetic algorithm framework, modified to operate alongside artificial predation experiments. In this system, predators freely interact with prey, and the order of attack determines the survival and reproduction of prey patterns into future generations. We demonstrate the feasibility of these methods with a case study, in which free-flying birds feed on artificial prey deployed in semi-natural conditions, against backgrounds differing in three-dimensional complexity. Wild predators reliably participated in this experiment, foraging for 11 to 16 generations of artificial prey and encountering a total of 1,296 evolved prey items. Changes in prey pattern across generations indicated improvements in several metrics of similarity to the background, and greater edge disruption, although effect sizes were relatively small. Computer-based replicates of these trials, with human volunteers, highlighted the importance of starting population parameters for subsequent evolution, a key consideration when applying these methods. Ultimately, these methods provide pathways for integrating complex genetic algorithms into more naturalistic predation trials. Customisable open-access tools should facilitate application of these tools to investigate a wide range of visual pattern types in more ecologically-relevant contexts.

Zika (ZIKV) and chikungunya (CHIKV) are arboviruses that cause infections in humans and can cause clinical complications, representing a worldwide public health problem. Aedes aegypti is the primary vector of these pathogens and Culex quinquefasciatus may be a potential ZIKV vector. This study aimed to evaluate fecundity, fertility, survival, longevity, and blood feeding activity in Ae. aegypti after exposure to ZIKV and CHIKV and, in Cx. quinquefasciatus exposed to ZIKV. Three colonies were evaluated: AeCamp (Ae. aegypti-field), RecL (Ae. aegypti-laboratory) and CqSLab (Cx. quinquefasciatus-laboratory). Seven to 10 days-old females from these colonies were exposed to artificial blood feeding with CHIKV or ZIKV. CHIKV caused reduction in fecundity and fertility in AeCamp and reduction in survival and fertility in RecL. ZIKV impacted survival in RecL, fertility in AeCamp and, fecundity and fertility in CqSLab. Both viruses had no effect on blood feeding activity. These results show that CHIKV produces a higher biological cost in Ae. aegypti, compared to ZIKV, and ZIKV differently alters the biological performance in colonies of Ae. aegypti and Cx. quinquefasciatus. These results provide a better understanding over the processes of virus-vector interaction and can shed light on the complexity of arbovirus transmission.

A role for exportin 4 (XPO4) in the pathogenesis of liver fibrosis was recently identified. We sought to determine changes in hepatic XPO4 promoter methylation levels during liver fibrosis. The quantitative real-time RT-PCR technique was used to quantify the mRNA level of XPO4. Additionally, pyrosequencing was utilized to assess the promoter methylation status of XPO4. The methylation rate of the XPO4 promoter was significantly increased with fibrosis in human and mouse models, while XPO4 mRNA expression negatively correlated with methylation of its promoter. DNA methyltransferases (DNMTs) levels (enzymes that drive DNA methylation) were upregulated in patients with liver fibrosis compared to healthy controls and in hepatic stellate cells upon transforming growth factor beta (TGFβ) stimulation. The DNA methylation inhibitor 5-Aza or specific siRNAs for these DNMTs led to restoration of XPO4 expression. The process of DNA methylation plays a crucial role in the repression of XPO4 transcription in the context of liver fibrosis development.

More than 250 million children will not meet their developmental potential due to poverty and malnutrition. Psychosocial stimulation has shown promising effects for improving development in children exposed to severe acute malnutrition (SAM) but programs are rarely implemented. In this study, we used qualitative methods to inform the development of a psychosocial stimulation programme to be integrated with SAM treatment in Mwanza, Tanzania. We conducted in-depth interviews with seven caregivers of children recently treated for SAM and nine professionals in early child development. We used thematic content analysis and group feedback sessions and organised our results within the Nurturing Care Framework. Common barriers to stimulate child development included financial and food insecurity, competing time demands, low awareness about importance of responsive caregiving and stimulating environment, poor father involvement, and gender inequality. Caregivers and professionals suggested that community-based support after SAM treatment and counselling on psychosocial stimulation would be helpful, e.g., how to create homemade toys and stimulate through involvement in everyday chores. Based on the findings of this study we developed a context-relevant psychosocial stimulation programme. Some issues identified were structural highlighting the need for programmes to be linked with broader supportive initiatives.

We study the relationship between reflectance and the degree of linear polarization of radiation that bounces off the surface of an unvarnished oil painting. We design a VNIR-SWIR (400 nm to 2500 nm) polarimetric reflectance imaging spectroscopy setup that deploys unpolarized light and allows us to estimate the Stokes vector at the pixel level. We observe a strong negative correlation between the S0 component of the Stokes vector (which can be used to represent the reflectance) and the degree of linear polarization in the visible interval (average -0.81), while the correlation is weaker and varying in the infrared range (average -0.50 in the NIR range between 780 and 1500 nm, and average -0.87 in the SWIR range between 1500 and 2500 nm). By tackling the problem with multi-resolution image analysis, we observe a dependence of the correlation on the local complexity of the surface. Indeed, we observe a general trend that strengthens the negative correlation for the effect of artificial flattening provoked by low image resolutions.

This research aimed to investigate the mediating function of Green Employee Empowerment (GEE) in the relationship between Green Human Resource Management practices (GHRM) and the environmental performance of small and medium-sized enterprises (SMEs) in Ghana, drawing on the Ability-Motivation-Opportunity (AMO) theory. This study assessed the hypotheses in the established research model using structural equation modeling based on data collected from 320 participants from small and medium-sized firms in Ghana. The study's results revealed that GHRM practices were significantly correlated with the firm's environmental performance. The study found significant GHRM's indirect consequences on environmental performance through GEE in all models examined. These findings suggest that GEE plays a crucial role in translating the impact of GHRM practices into improved environmental performance. The study overlooked other potential mediators or moderators in the relationship between GHRM practices and environmental performance, focusing on GEE. To better understand the complex dynamics behind GHRM techniques' environmental performance, future research might examine business culture, leadership style, and employee sustainability attitudes.

BackgroundDespite the implementation of patient-centred care, mental health issues remain a significant risk factor and comorbidity for Tuberculosis (TB) disease. Mental health issues being co-morbidities to TB are likely to increase the disease burden of the affected population. This study therefore investigated the prevalence and impact of mental health issues in Tuberculosis (TB) patients.MethodsThis cross-sectional study design used mixed methods in data collection. The study used structured questionnaires, key informant interviews and focus group discussions. 127 TB patients were purposively selected from a group of patients who previously recovered successfully, with a history of relapse or are currently on TB treatment in high-volume facilities in Homa Bay, Busia and Kakamega Counties. 30 Key informant interviews were conducted with Healthcare workers. Quantitative data analysis was done using STATA version 14. Thematic analysis was employed to analyze qualitative data using NVivo version 10.ResultsThe findings showed that the most common mental health issues affecting TB patients were anxiety (66%) and depression (55%), which were commonly experienced during the presumptive stage of TB. Qualitative data revealed that stigma was the main barrier that hindered TB patients from accessing care. TB patients articulated the benefits of support structures ranging from positive encouragement, reminders on taking drugs, accompaniment to the clinic, and financial support in TB management. Furthermore, the study established that the majority of Health Care Workers (HCWs) were not prepared to handle TB patients' mental issues, a gap that is likely to impact the quality of care TB patients receive.ConclusionThe study established that mental health issues impact TB treatment outcomes. Healthcare systems should prioritize the integration of mental health care into TB programs to address the high prevalence of mental health issues among TB patients.

Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC. The aim of the present study was to develop a long-term, patient-derived explant (PDE) model of early-stage EC and demonstrate its use for investigating predictive biomarkers for a current non-surgical treatment option, the levonorgestrel intra-uterine system (LNG-IUS). Fresh tumour specimens were obtained from patients with early-stage endometrioid EC. Tumours were cut into explants, cultured on media-soaked gelatin sponges for up to 21 days and treated with LNG. Formalin-fixed, paraffin embedded (FFPE) blocks were generated for each explant after 21 days in culture. Tumour architecture and integrity were assessed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). IHC was additionally performed for the expression of five candidate biomarkers of LNG resistance. The developed ex vivo PDE model is capable of culturing explants from early-stage EC tumours long-term (21 Days). This model can complement existing models and may serve as a tool to validate results obtained in higher-throughput in vitro studies. Our study provides the foundation to validate the extent to which EC PDEs reflect patient response in future research.