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Mortality and Predictors of Mortality Among COVID-19 Patients in Kiambu County, Kenya:COVID
Get PDFSARS-CoV-2 continues to circulate with new variants of uncertain transmissibility and virulence arising over time and resulting in varying morbidity and mortality between and within countries. This study aimed to identify the predictors of mortality among hospitalized COVID-19 patients across the first five waves of the pandemic. We conducted a retrospective cohort study at Tigoni Level 4 Hospital in Kenya. The study included patients admitted between June 2020 to August 2022 who tested positive for SARS-CoV-2. Sociodemographic and clinical data were abstracted from patient records at the time of admission and throughout their hospital stay. We employed Cox proportional hazard regression analysis to estimate the time to event (discharge or death) and identify predictors of mortality. Both time-varying and non-time-varying covariates were included in the models. A total of 1985 patients were admitted, of whom 557 (28%) died. The median hospital stay was 4 (1.0–8.0) days and 9 (5.0–13.0) days for patients who died and those who were discharged alive, respectively. Compared to patients admitted during wave 1, those admitted during the subsequent waves had high risk of death estimated at adjusted HR: 1.66 (95% CI 1.2, 2.54), 5.17 (95% CI 3.55, 7.53), 2.62 (95% CI 1.87, 3.67), and 2.17 (95% CI 1.51, 3.11) for waves 2, 3, 4, and 5, respectively. A proportion of patients presented with persistent chest pain, cough, and hypoxia and continued oxygen therapy for more than two months. In addition, patients who had persistent fever, hypoxia, cough, and fatigue had a significant mortality risk (adjusted HR: 3.00; 95% CI: 1.81–4.98; HR: 1.97; 95% CI: 1.73–2.26; HR: 1.47; 95% CI: 1.24–1.75; HR: 1.64; 95% CI: 1.05–2.54). Conversely, patients who had low oxygen saturation and received oxygen at admission had a 76% (HR: 0.24; 95% CI: 0.13–0.42) reduction in mortality risk and in addition patients whose treatment was altered had a 49% reduction in mortality risk (HR: 0.51; CI: 0.45–0.58). Our study highlights the benefits of oxygen therapy on the outcome of COVID-19 patients and justifies the need to increase investments in oxygen especially in low-and-middle-income countries. It also confirms the need to analyze the pandemic by the different waves
Opportunities for optimising care transitions of adults with multiple long-term conditions:a qualitative interview study
Get PDFBackground: The number of adults with multiple long-term conditions (MLTC) who experience frequent care transitions is rising. Improving care transitions for adults MLTC is important because transitions between and within care settings commonly lead to preventable adverse events. We explored multidisciplinary professional perspectives and experiences of managing care transitions for patients with MLTC to identify opportunities for improvement. Methods: Qualitative interviews with 30 health and social care professionals in four Scottish integrated Health and Social Care Partnerships. Data were collected between May 2023 and March 2024. Thematic analysis was used, guided by the Sustainable Integrated Chronic Care Models for Multimorbidity: Delivery, Financing, and Performance (SELFIE) framework. Results: Care transitions were described as lacking person-centredness and consistency. Variability in decisions on cross-boundary acute care pathways was largely attributed to human factors (e.g., ease of arranging referrals, a lack of trust or awareness of Hospital at Home service) by hospital specialist staff, but to clinical complexity and home environment limitations (physical and social) by community staff. Ineffective interprofessional relationships and poor communication across services were common experiences, significantly driven by a lack of integration between IT systems affecting timely access to information and by services having different priorities and pressures. Workforce shortages, knowledge gaps in managing MLTC, and long-standing capacity issues in social care were identified as important barriers to effectively managing transitions. Conclusions: We identified multiple system-level barriers to providing high-quality and safe care transitions. We proposed key improvement opportunities, highlighting the need for using system engineering and systems thinking approaches, underpinned by the active engagement of patients, carers, professionals, and wider stakeholders to drive meaningful and sustainable change in transitions of care.<br/
Identification and replication of sex-dimorphic protein quantitative trait loci across multiple ancestries and their associations with diseases
Get PDFMales and females exhibit differences in proteome profiles associated with disease risk. However, sex-dimorphic protein quantitative trait loci (SD-pQTL) and their effects on sex differences in health disorders have not been thoroughly investigated. We conducted a sex-stratified, genome-wide association study on 2,922 proteins using data from 30,272 individuals of Caucasian ancestry from the UK Biobank and compared the estimated effects on protein levels of these variants in the men and women to identify SD-pQTLs. The identified SD-pQTLs were replicated using data from two Japanese cohorts (comprising 2,886 and 1,394 individuals, respectively), as well as from 1,990 Finnish, 630 South Asian, and 662 Black ancestry individuals. Sex-dimorphic pleiotropy and the causal relationship between protein levels and health disorders were assessed using the identified SD-pQTLs. We identified 113 SD-pQTLs associated with 65 proteins. Of the 113 SD-pQTLs, 52 were significant in both sexes, five were not significant in either sex, and 42 and 14 were significant only in males and females, respectively. Variant rs2270416 was significantly associated with the CDH15 protein in both sexes but showed opposite effect direction in men and women. Of the 113 SD-pQTLs identified, a total of 41 were replicated in a meta-analysis encompassing Japanese, South Asian, and Black ancestry individuals. SD-pQTLs for proteins APOE (rs157581) and SNAP25 (rs4420638) exhibited sex-dimorphic associations with dementia, indicating sex dimorphic pleiotropy in both proteins and health disorders. From sex-stratified Mendelian randomization using the SD-pQTLs, proteins NCAM1 and PZP showed significant causal relationship with dementia in males and females, respectively. The present study provides evidence of sex-dimorphic genetic architecture in protein-level regulation, elucidating the proteo-genetic architecture for sex differences in human variation.</p
Wild house mice have a more dynamic and aerotolerant gut microbiota than laboratory mice
Get PDFThe mammalian gut microbiota is a complex microbial community with diverse impacts on host biology. House mice (Mus musculus) are the major model organism for research on mammals, but laboratory domestication has altered their gut microbiota from that of their wild counterparts. Knowledge about how and why the gut microbiota of this species varies between lab and wild settings and among natural populations could improve its utility as a model organism. Here, we use a large dataset comprising over 800 house mouse samples from multiple laboratory facilities and strains and wild mice from mainland and island populations to investigate gut microbiota variation in this species across contrasting genetic and environmental settings. Across geographically disparate populations, we find that wild mice possess a gut microbiota that is compositionally distinct, displays a higher relative abundance and richness of aerotolerant taxa, and is taxonomically and functionally more diverse than that of lab mice. Longitudinally sampled wild mice also display markedly higher temporal turnover in microbiota composition than lab mice. Wild mice from oceanic islands harboured microbiotas that differed subtly from those of mainland wild mice and were more divergent from lab mouse microbiotas. These findings highlight much greater spatial and temporal turnover of gut microbes in wild compared to laboratory mice
A chromosomal level genome assembly of Nguni Sheep, Ovis aries
Get PDFNguni sheep (Ovis aries) are indigenous to the Southern Africa region and common within the smallholder and poor resources farming systems. They are well adapted to different agroecological regions. However, limited genomic resources such as high-quality reference genomes have hindered our understanding of its adaptation and establishment of an effective breeding program. To address this, we assembled a chromosomal-level genome of Nguni sheep using a combination of PacBio HiFi reads and Omni-C reads. The genome size was estimated to be 2.9 Gb with a contig/scaffold N50 74 Mb and 99.6 Mb and a genome completeness of 96.1%, as estimated by the Benchmarking Universal Single-Copy Orthologs (BUSCO) program. The final genome encompassed a total of 25,926 protein-coding genes. The findings of this study provide a valuable genomic resource for understanding the adaptability of the Nguni sheep and the establishment of effective breeding programs.</p
Enhancing international student experience:Co-constructing community through peer mentoring
Get PDFThis study is part of a larger project that examines a school-wide peer support scheme conducted in a higher education institution in the UK. Through providing peer mentoring from PhD students to postgraduate taught (PGT) students, this project addressed the need to enhance international student experience. This study focused on PhD students’ perspectives, and data were collected from three sources: PhD participants’ (n = 7) reflective journals, mid-way focus group discussion, and related documents. Thematic analysis was adopted to analyse the data. Key findings of the study include the community-building scheme yielded reciprocal benefits for the two sides of communication: both PGT and PhD students gained benefits in terms of academic, psychological, and intercultural communication and experience. Findings were detailed in topics that international students were commonly confronted with. In addition, the benefits and challenges that PhD students reported were scrutinised in order to provide suggestions for further peer support initiatives
NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis
Get PDFIn eukaryotes, the nucleocytoplasmic export of bulk poly(A)+-mRNAs through the nuclear pore complex is mediated by the ubiquitously expressed NXT1-NXF1 heterodimer. In humans, NXT1 has an X-chromosomal paralog, NXT2, which exhibits testis-enriched expression, suggesting a role in spermatogenesis. Here, we report the in vivo interaction of NXT2 with crucial components of the nuclear export machinery, including NXF1, the testis-specific NXF1 paralogs NXF2 and NXF3, and nuclear pore complex proteins. Binding to NXF2 and NXF3 is mediated by the NTF2-like domain of NXT2. By identifying infertile men with loss-of-function variants in NXT2 and NXF3, we link the impaired NXT2-NXF activity to disturbed germ cell development. The predominant absence of germ cells in men with NXT2 deficiency indicates its critical function already during fetal or first steps of germ cell development. In contrast, loss of NXF3 affects later stages of spermatogenesis, resulting in quantitatively and qualitatively impaired sperm production
Pregnancy and liver health: delivering new collaborations to advance the MASLD and MASH field
Get PDFHousing density affects the survivorship post infection of Drosophila melanogaster males in a pathogen dependent manner
Get PDFThe impact of social interaction on physiology and behaviour has been widely studied in social insects, but less so in non-eusocial insects. Group housing can signal higher infection risk and reproductive competition, potentially leading to context-dependent trade-offs between reproductive versus immune investment. In this study, we housed Drosophila melanogaster males singly or in groups of two or sixteen for two days and assessed their post infection survival. We found that singly held males exhibited higher mortality post-infection with Pseudomonas entomophila compared to males housed in groups of sixteen. Males held singly or as pairs did not significantly differ in their mortality. However, there was no difference in mortality between the three groups when the pathogen was Bacillus thuringiensis. Singly held males showed elevated levels of cat1, sod and puc and lower levels of rel, indicating elevated stress levels and lower immunity in them. Environmental factors other than the housing density did not account for the difference in survivorship between singly held and group-held flies post-infection with P. entomophila. We observed no trade-off between reproductive investment and post-infection survivorship. Thus, our results show a complex interplay between social isolation, stress related mechanisms and immune function of a non-eusocial insect
Verbal Collaboration in Same- and Mixed-Neurotype Groups of Autistic and Non-Autistic Adults
Get PDFBackground: Research suggests that some autistic adults communicate more effectively and build stronger rapport with other autistic individuals than with non-autistic people. This suggests that outcomes for autistic people in group settings may depend on the diagnostic composition of the group. Here, we examined verbal collaboration among autistic and non-autistic adults in same- and mixed-neurotype groups during a shared task. Methods: We assigned 136 adults (73 autistic, 63 non-autistic) to 34 four-person groups: all autistic, all non-autistic, majority autistic, or majority non-autistic. To control for selective disclosure, an experimenter informed participants of their group’s diagnostic composition before the study without revealing individual diagnoses. Researchers video recorded groups during a 5-minute Jenga tower-building task, and participants reported their rapport with the group. Researchers transcribed and coded the videos for collaborative speech using a validated coding scheme. Results: Preregistered analyses revealed that autistic participants expressed more positive opinions about the group and their own contributions than did non-autistic participants. Non-autistic participants expressed more negative group evaluations and elicited more building ideas. Participants in mixed-neurotype groups directed more negativity toward others than participants in same-neurotype groups. Autistic—but not non-autistic—participants verbalized more negativity in mixed groups. Exploratory correlations revealed links between aspects of collaborative speech and rapport. Discussion: Autistic adults expressed greater overall positivity but expressed more negativity in mixed group settings. These findings support evidence that autistic people often experience better rapport in all-autistic groups and may be more sensitive to mixed group environments than non-autistic people.</p
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