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AIM: To identify the barriers and facilitators of deceased organ donation among the Muslim community living globally. METHOD: A systematic search was undertaken in databases such as CINAHL, Medline with full text, Global Health and PsycINFO via EBSCO; Scopus via Elsevier; Web of Science via Clarivate; and PubMed via US National Library of Medicine National Institute of Health were used to retrieve the studies on the 31st of December 2023. Apart from these databases two other journals, the Saudi Journal of Kidney Diseases and Transplantation, and the Journal of Experimental and Clinical Transplantation were also used to search for relevant studies. Quantitative and qualitative studies that addressed the aim of the present review published from the 30th of April 2008 were included. RESULTS: Of the 10,474 studies, 95 studies were included in the review. The following five themes were generated based on narrative synthesis: 1) knowledge of organ donation, 2) willingness to donate, 3) community influence, 4) bodily influence, and 5) religious influence. While individuals view organ donation as a noble act, societal influences significantly impact their decision to register. Concerns include religious permissibility, potential misuse for commercial purposes, and the dignity and respect given to the deceased donor's body. CONCLUSIONS: This review finds deceased organ donation decisions in this population are collective, influenced by religious views, and hindered by uncertainty. Interventional studies on strategies to address uncertainty could help us identify best practices for this population to improve deceased organ donation. Rather than an individual approach among this population, a whole-system approach, tailored-made evidence-guided community engagement could improve donation rates.
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Oxytocin and cortisol are hormones that can influence cognition and behavior, but the relationships between endogenous concentrations and individual differences in cognitive and behavioral phenotypes remain poorly understood. Across mammals, oxytocin has important roles in diverse social behaviors, and in dogs, it has been implicated in human-oriented behaviors such as social gaze and point-following. Cortisol, an end-product of the hypothalamic-pituitary-adrenal (HPA) axis, is often studied in relation to temperament and emotional reactivity, but it is also known to modulate executive functions. In this study, we measured basal fecal cortisol (n = 247) and plasma oxytocin (n = 249) in dog puppies from a pedigreed population (Canine Companions ®). We collected cognitive and behavioral data from these subjects (n = 247), including measures of human-oriented social cognition, memory, inhibitory control, perceptual discriminations, and temperament. Oxytocin concentrations were estimated to be very highly heritable (h2 = 0.90-0.99) and cortisol concentrations were estimated to be moderately-highly heritable (h2 = 0.43-0.47). Bayesian mixed models controlling for relatedness revealed that oxytocin concentrations were positively associated with spatial working memory and displayed a negative quadratic relationship with behavioral laterality, but no credible associations were seen for social measures. Cortisol concentrations exhibited a negative linear relationship with performance on an inhibitory control task and a negative quadratic relationship with bold behavioral reactions to a novel object. Collectively, our results suggest that individual differences in oxytocin and cortisol concentrations are under strong genetic control in dogs and are associated with phenotypic variation in aspects of temperament, behavioral laterality, and executive function.
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The gut microbiome is a plastic phenotype; gut microbial composition is highly variable across an individual host's lifetime and between host social groups, and this variation has consequences for host health. However, we do not yet fully understand how longitudinal microbial dynamics and their social drivers may be influenced by ecological stressors, such as habitat degradation. Answering these questions is difficult in most wild animal systems, as it requires long-term collections of matched host, microbiome, and environmental trait data. To test if temporal and social influences on microbiome composition differ by the history of human disturbance, we leveraged banked, desiccated fecal samples collected over 5 months in 2004 from two ecologically distinct populations of wild, red-bellied lemurs (Eulemur rubriventer) that are part of a long-term study system. We found that social group explained more variation in microbiome composition than host population membership did, and that temporal variation in common microbial taxa was similar between populations, despite differences in history of human disturbance. Furthermore, we found that social group membership and collection month were both more important than individual lemur identity. Taken together, our results suggest that synchronized environments use can lead to synchronized microbial dynamics over time, even between habitats of varying quality, and that desiccated samples could become a viable approach for studying primate gut microbiota. Our work opens the door for other projects to utilize historic biological sample data sets to answer novel temporal microbiome questions in an ecological context.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness, skin rashes, and cardiac, endocrine, renal and hepatic manifestations. The treatment of this syndrome remains challenging. A multidisciplinary approach to address combinations of symptoms affecting multiple organ systems has been widely adopted. This narrative review aims to bridge the gap surrounding the broad treatment approaches by providing an overview of multidisciplinary management strategies for the most common long COVID conditions.
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BACKGROUND: A number of children experience difficulties with social communication and this has long-term deleterious effects on their mental health, social development and education. The E-PLAYS-2 study will test an intervention ('E-PLAYS') aimed at supporting such children. E-PLAYS uses a dyadic computer game to develop collaborative and communication skills. Preliminary studies by the authors show that E-PLAYS can produce improvements in children with social communication difficulties on communication test scores and observed collaborative behaviours. The study described here is a definitive trial to test the effectiveness and cost-effectiveness of E-PLAYS delivered by teaching assistants in schools. METHODS: The aim of the E-PLAYS-2 trial is to establish the effectiveness and cost-effectiveness of care as usual plus the E-PLAYS programme, delivered in primary schools, compared to care as usual. Cluster-randomisation will take place at school level to avoid contamination. The E-PLAYS intervention will be delivered by schools' teaching assistants. Teachers will select suitable children (ages 5-7 years old) from their schools using guidelines provided by the research team. Assessments will include blinded language measures and observations (conducted by the research team), non-blinded teacher-reported measures of peer relations and classroom behaviour and parent-reported use of resources and quality of life. A process evaluation will also include interviews with parents, children and teaching assistants, observations of intervention delivery and a survey of care as usual. The primary analysis will compare pragmatic language scores for children who received the E-PLAYS intervention versus those who did not at 40 weeks post-randomisation. Secondary analyses will assess cost-effectiveness and a mixed methods process evaluation will provide richer data on the delivery of E-PLAYS. DISCUSSION: The aim of this study is to undertake a final, definitive test of the effectiveness of E-PLAYS when delivered by teaching assistants within schools. The use of technology in game form is a novel approach in an area where there are currently few available interventions. Should E-PLAYS prove to be effective at the end of this trial, we believe it is likely to be welcomed by schools, parents and children. TRIAL REGISTRATION: ISRCTN 17561417, registration date 19th December 2022. PROTOCOL VERSION: v1.1 19th June 2023.
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Comportamento Cooperativo , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Comunicação , Análise Custo-Benefício , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtorno de Comunicação Social/terapiaRESUMO
Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement. Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy. Design, Setting, and Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020. Data were analyzed from December 2022 to December 2023. Structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) were evaluated in an independent neuroimaging group. The FLAME cohort includes 2809 autopsied individuals; included in this study were neuropathologically diagnosed AD cases (FLAME-AD). A digital pathology subgroup of FLAME-AD cases was derived for glial activation analyses. Main Outcomes and Measures: Clinicopathologic factors of heterogeneity that inform patient history and neuropathologic evaluation of AD; CLix score (lower, relative cortical predominance/hippocampal sparing vs higher, relative cortical sparing/limbic predominant cases); neuroimaging measures (ie, structural MRI and tau-PET). Results: Of the 2809 autopsied individuals in the FLAME cohort, 1361 neuropathologically diagnosed AD cases were evaluated. A digital pathology subgroup included 60 FLAME-AD cases. The independent neuroimaging group included 93 cases. Among the 1361 FLAME-AD cases, 633 were male (47%; median [range] age at death, 81 [54-96] years) and 728 were female (53%; median [range] age at death, 81 [53-102] years). A younger symptomatic onset (Spearman ρ = 0.39, P < .001) and faster decline on the Mini-Mental State Examination (Spearman ρ = 0.27; P < .001) correlated with a lower CLix score in FLAME-AD series. Cases with a nonamnestic syndrome had lower CLix scores (median [IQR], 13 [9-18]) vs not (median [IQR], 21 [15-27]; P < .001). Hippocampal MRI volume (Spearman ρ = -0.45; P < .001) and flortaucipir tau-PET uptake in posterior cingulate and precuneus cortex (Spearman ρ = -0.74; P < .001) inversely correlated with CLix score. Although AD cases with a CLix score less than 10 had higher cortical tangle count, we found lower percentage of CD68-activated microglia/macrophage burden (median [IQR], 0.46% [0.32%-0.75%]) compared with cases with a CLix score of 10 to 30 (median [IQR], 0.75% [0.51%-0.98%]) and on par with a CLix score of 30 or greater (median [IQR], 0.40% [0.32%-0.57%]; P = .02). Conclusions and Relevance: Findings show that AD heterogeneity exists along a continuum of corticolimbic tangle distribution. Reduced CD68 burden may signify an underappreciated association between tau accumulation and microglia/macrophages activation that should be considered in personalized therapy for immune dysregulation.
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Doença de Alzheimer , Imageamento por Ressonância Magnética , Neuroglia , Tomografia por Emissão de Pósitrons , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Neuroglia/patologia , Neuroglia/metabolismo , Estudos Transversais , Estudos Retrospectivos , Emaranhados Neurofibrilares/patologia , Proteínas tau/metabolismo , Pessoa de Meia-Idade , Neuroimagem , Estudos de Coortes , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/metabolismo , AutopsiaRESUMO
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) share many clinical, pathological, and genetic features, but a detailed understanding of their associated transcriptional alterations across vulnerable cortical cell types is lacking. Here, we report a high-resolution, comparative single-cell molecular atlas of the human primary motor and dorsolateral prefrontal cortices and their transcriptional alterations in sporadic and familial ALS and FTLD. By integrating transcriptional and genetic information, we identify known and previously unidentified vulnerable populations in cortical layer 5 and show that ALS- and FTLD-implicated motor and spindle neurons possess a virtually indistinguishable molecular identity. We implicate potential disease mechanisms affecting these cell types as well as non-neuronal drivers of pathogenesis. Finally, we show that neuron loss in cortical layer 5 tracks more closely with transcriptional identity rather than cellular morphology and extends beyond previously reported vulnerable cell types.
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Esclerose Lateral Amiotrófica , Degeneração Lobar Frontotemporal , Córtex Pré-Frontal , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Demência Frontotemporal/genética , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/metabolismo , Degeneração Lobar Frontotemporal/patologia , Perfilação da Expressão Gênica , Neurônios/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Análise da Expressão Gênica de Célula ÚnicaRESUMO
OBJECTIVE: The aim was to evaluate representation of women in otolaryngology by examining authorship of research publications and presentations, awards, research grants, leadership, and membership in related organizations. METHODS: Authorship was reviewed from articles published in three otolaryngology journals from 2000 through 2021 to assess the frequency and percentages of female and combination of male and female gender authorship. Gender was evaluated for poster and scientific abstract presentations from 2007 to 2021. Gender representation was reviewed for institutional and society leadership positions, award, and grant recipients in the American Laryngological Society (ALA). Changes in the frequency of female and combination of male and female gender authorship over time were examined with Cochran-Armitage test for trend. RESULTS: A total of 16,921 articles, 1,017 presentations, 480 leadership positions, 129 president positions, and 1,137 awards and grants were studied. Women were first authors in 4,153 (24.9%) and last authors in 2,935 (17.8%) published articles for which gender could be determined. Women were first authors in 372 (37.4%) presentations and last authors in 199 (20.2%). Most presentations had a combination of male and female presentation authorship (630, 68%). Women held 69 (14.4%) leadership positions. Of the award and grant recipients, 327 (28.8%) were female. Significant trends were observed for increasing female representation (first authorship publications increased 69.9% from 2000 to 2020, first authorship presentations increased 73.9% from 2007 to 2013, p < 0.001; leadership and awards from 3% to 18% representation, p = 0.02). CONCLUSION: The proportion of women receiving awards and holding leadership positions is increasing. Efforts that promote gender diversity may further increase representation of women in otolaryngology literature and among the grant and award winners. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2144-2152, 2024.
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Otolaringologia , Publicações , Humanos , Masculino , Feminino , Autoria , LiderançaRESUMO
A repeat expansion in the C9orf72 (C9) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we investigate single nucleus transcriptomics (snRNA-seq) and epigenomics (snATAC-seq) in postmortem motor and frontal cortices from C9-ALS, C9-FTD, and control donors. C9-ALS donors present pervasive alterations of gene expression with concordant changes in chromatin accessibility and histone modifications. The greatest alterations occur in upper and deep layer excitatory neurons, as well as in astrocytes. In neurons, the changes imply an increase in proteostasis, metabolism, and protein expression pathways, alongside a decrease in neuronal function. In astrocytes, the alterations suggest activation and structural remodeling. Conversely, C9-FTD donors have fewer high-quality neuronal nuclei in the frontal cortex and numerous gene expression changes in glial cells. These findings highlight a context-dependent molecular disruption in C9-ALS and C9-FTD, indicating unique effects across cell types, brain regions, and diseases.
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Esclerose Lateral Amiotrófica , Demência Frontotemporal , Humanos , Demência Frontotemporal/genética , Esclerose Lateral Amiotrófica/genética , Proteína C9orf72/genética , Transcriptoma/genética , Epigenoma , MutaçãoRESUMO
BACKGROUND: The COVID-19 pandemic has led to changes in health behaviours, which include eating patterns and nutrition, smoking, alcohol consumption, sleeping patterns, physical activity and sedentary behaviour. There is a dearth of evidence reporting the impact of COVID-19 on the health behaviour of Black, Asian and minority ethnic (BAME) communities. This scoping review synthesises the available evidence on the impact of COVID-19 on the changes in health behaviours among BAME communities in the UK. METHODS: Following a keyword strategy, 16 electronic databases were searched for articles that met the screening criteria. These articles were then reviewed in full text. Empirical studies that assessed COVID-19 related health behaviour changes among BAME communities in the UK, conducted during the COVID-19 pandemic between July 2020 and August 2021 and published in English language, were set as inclusion criteria. An initial 2160 studies were identified in the selected databases. After removing duplications and screening the title and abstracts of the 2154 studies, only 4 studies were selected to be reviewed as they met the inclusion criteria. The included studies employed different sample sizes which ranged from N = 47 to N = 30,375 and reported several health behaviour changes. Out of the 4 included studies, 3 studies included BAME groups within their sample as a subgroup while one study focused specifically on BAME groups. RESULTS: The scoping review found that there were lower levels of physical activity among BAME groups compared to the White ethnic groups. About 41.7% of BAME groups reported drinking less alcohol than usual compared to their white counterparts who were 34%. Study participants from BAME backgrounds had the greatest effect of COVID-19 on decisions to purchase healthier food compared to those from white backgrounds whose decisions on purchasing healthier food were least affected. Some participants reported an increase in positive hygiene practices due to the COVID-19 pandemic. CONCLUSION: COVID-19 had a significant impact on the health behaviours of BAME groups especially during the lockdowns as they reported changes to behaviour such as low levels of physical activities. Hence, it is important to promote health awareness among BAME groups to encourage healthy living. In addition, programmes such as physical fitness activities that favour BAME groups should be put in place, for example BAME women's walking groups to encourage people from BAME backgrounds to engage in physical activities. Furthermore, healthy food programmes such as food parcels can be given to people from BAME backgrounds who are not able to afford healthy food due to the impact of COVID-19. Nonetheless, the COVID-19 pandemic has increased positive hygiene among BAME groups which is important in preventing other diseases and infections.
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COVID-19 , Feminino , Humanos , COVID-19/epidemiologia , Promoção da Saúde , Pandemias , Controle de Doenças Transmissíveis , Grupos Minoritários , Comportamentos Relacionados com a Saúde , Reino Unido/epidemiologiaRESUMO
INTRODUCTION: Muslims have been shown to have less favourable attitudes towards organ donation and are less likely to consent to donate their organs. While several studies have been undertaken globally to identify the barriers and facilitators of organ donation, no systematic review has synthesised this evidence to date. Therefore, this systematic review aims to identify the barriers and facilitators of organ donation among Muslims living globally. METHODS AND ANALYSIS: This systematic review will include cross-sectional surveys and qualitative studies published between 30 April 2008 and 30 June 2023. Evidence will be restricted only to studies reported in English. An extensive search strategy will be used in PubMed, CINAHL, Medline, Scopus, PsycINFO, Global Health and Web of Science, as well as specific relevant journals that may not be indexed in these databases. A quality appraisal will be undertaken using Joanna Briggs Institute quality appraisal tool. An integrative narrative synthesis will be used to synthesise the evidence. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Institute for Health Research Ethics Committee (IHREC) (IHREC987), University of Bedfordshire. The findings of this review will be disseminated widely through peer-reviewed journal articles and leading international conferences. PROSPERO REGISTRATION NUMBER: CRD42022345100.
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Islamismo , Obtenção de Tecidos e Órgãos , Humanos , Estudos Transversais , Pesquisa Qualitativa , Saúde Global , Projetos de Pesquisa , Revisões Sistemáticas como AssuntoRESUMO
This study aims to understand the experiences of professionals involved in caring for families of children with life-limiting illnesses to ascertain unmet needs, access issues and expectations of services.A phenomenological approach comprising semi-structured interviews with professionals from various services was used. Interviews that happened between July and November 2018 were audio-recorded, transcribed verbatim and thematically analysed based on descriptive phenomenology.In total, 29 interviews were conducted. Findings showed how essential collaborative working was for becoming a team around the child. Barriers to this include complex working relationships, overprotectiveness of families, roles and responsibilities and use of independent care records. The pressures of waiting times and the impact of staffing shortages affected the experiences of providing care. The reality of meeting families' expectations was shaped by family networking, online research and previous services resistance, which was influential in more challenging interactions. Expectations of care were also impacted by misunderstandings and anxieties surrounding access to services. Overall, professionals were concerned about families being used as a bottomless caring resource and stressed the need for short breaks to alleviate parents.Interventions that educate families and professionals on these services and how they can benefit the child and family would be well received.
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Purpose: To investigate the quantitative and qualitative efficacy of finger-prick autologous blood (FAB) eye drops versus conventional medical therapy for the treatment of severe dry eye disease (DED). Methods: Two centre, single masked, randomised controlled trial. Sixty patients in total were recruited with thirty patients (sixty eyes) treated with FAB eye drops four times per day in addition to their conventional DED treatment, and thirty patients (fifty-eight eyes) served as control subjects on conventional treatment alone. Ocular surface disease index (OSDI), Schirmer's test, fluorescein ocular staining grade (OCSG) Oxford schema and fluorescein tear film break-up time (TBUT), were performed at baseline, at 4 and 8 weeks. Results: OSDI scores significantly decreased in the FAB arm by greater than -17.68 (-37.67 to -2.96, p=0.02) compared to the control arm. There were greater improvements in OCSG and TBUT in the FAB arm but these were non-significant (p>0.05). Conclusion: This feasibility study demonstrates adding FAB eye drops to conventional medical therapy for DED improves mean OSDI symptom score compared to conventional medical therapy alone. It may have particular use in settings where serum is unobtainable. An adequately powered and well-designed randomised trial is needed to further evaluate the long-term clinical benefit of FAB.
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Background: Behavioural science and its contribution towards improving public health is receiving increased recognition. Yet, the translation of these insights into public health practice is under-researched. This study explored the factors influencing the use of behavioural science within public health at a local authority level. Methods: Fourteen local authority staff (n = 13 female) in the south of England participated in semi-structured interviews, which were analysed inductively to identify key themes. These were later mapped deductively to the COM-B model and Theoretical Domains Framework. Findings: Nine themes were identified as factors that influence the use of behavioural science in local authority public health: (1) "Limited past experience," (2) "Narrow understanding," (3) "Perceived value of behavioural science," (4) "Translational gap from theory-to-practice," (5) "No protected time," (6) "Old ways of working," (7) "Political influence and organisational culture," (8) "Relationships with key stakeholders," (9) "Access to behavioural science resources". Deductive mapping of these themes revealed that five of the COM constructs (excluding Physical Capability) and eleven of the TDF domains influenced behavioural science use, with "Social influences" and "Knowledge" being the most prominent. Discussion: Use of behavioural science within local authority public health practice is limited and inconsistent. For it to be successfully implemented, there must be an understanding of its role and value, alongside strategies to overcome a translational gap from theory to practice. Public health teams would benefit from protected time to enable application and strategies to break old habits of using a common-sense approach. System-wide buy-in, particularly related to senior leadership and system partners is needed, which would benefit from organisational and political culture change. Training opportunities, practical resources and expert in-house support should be considered a priority across public health teams.
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Ciências do Comportamento , Saúde Pública , Humanos , Feminino , Liderança , Reino Unido , InglaterraRESUMO
Formyl peptide receptor 2 (FPR2) plays an integral role in the transition of macrophages from a pro-inflammatory program to one that is pro-resolving. FPR2-mediated stimulation of resolution post myocardial infarction has demonstrated efficacy in rodent models and is hypothesized to reduce progression into heart failure. FPR2 agonists that promote long-lasting receptor internalization can lead to persistent desensitization and diminished therapeutic benefits. In vitro signaling profiles and propensities for receptor desensitization of two clinically studied FPR2 agonists, namely, BMS-986235 and ACT-389949, were evaluated. In contrast to BMS-986235, pre-stimulation with ACT-389949 led to a decrease in its potency to inhibit cAMP production. Moreover, ACT-389949 displayed greater efficacy for ß-arrestin recruitment, while efficacy of Gi activation was similar for both agonists. Following agonist-promoted FPR2 internalization, effective recycling to the plasma membrane was observed only with BMS-986235. Use of G protein-coupled receptor kinase (GRK) knock-out cells revealed a differential impact of GRK2 versus GRK5/6 on ß-arrestin recruitment and Gi activation promoted by the two FPR2 agonists. In vivo, decreases of granulocytes in circulation were greatly diminished in mice treated with ACT-389949 but not for BMS-986235. With short-term dosing, both compounds induced a pro-resolution polarization state in cardiac monocyte/macrophages post myocardial infarction. By contrast, with long-term dosing, only BMS-986235 preserved the infarct wall thickness and increased left ventricular ejection fraction in a rat model of myocardial infarction. Altogether, the study shows that differences in the desensitization profiles induced by ACT-389949 and BMS-986235 at the molecular level may explain their distinct inflammatory/pro-resolving activities in vivo.
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While several farnesoid X receptor (FXR) agonists under clinical investigation for the treatment of nonalcoholic steatohepatitis (NASH) have shown beneficial effects, adverse effects such as pruritus and elevation of plasma lipids have limited their clinical efficacy and approvability. Herein, we report the discovery and preclinical evaluation of compound 32 (BMS-986339), a nonbile acid FXR agonist with a pharmacologically distinct profile relative to our previously reported agonist BMS-986318. Compound 32 exhibited potent in vitro and in vivo activation of FXR, albeit with a context-dependent profile that resulted in tissue-selective effects in vivo. To our knowledge, this is the first report that demonstrates differential induction of Fgf15 in the liver and ileum by FXR agonists in vivo. Compound 32 demonstrated robust antifibrotic efficacy despite reduced activation of certain genes in the liver, suggesting that the additional pharmacology of BMS-986318 does not further benefit efficacy, possibly presenting an opportunity for reduced adverse effects. Further evaluation in humans is warranted to validate this hypothesis.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Receptores Citoplasmáticos e NuclearesRESUMO
MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, Iââ2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, Iââ2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results.
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COVID-19 , Síndrome do Desconforto Respiratório , Idoso , COVID-19/terapia , Terapia Baseada em Transplante de Células e Tecidos , Feminino , Humanos , Masculino , Síndrome do Desconforto Respiratório/terapiaRESUMO
OBJECTIVES: To understand the barriers towards deceased organ donation among Indians living globally. DESIGN: Integrative systematic review using narrative synthesis. DATA SOURCES: CINAHL, Medline full-text, PsycInfo, Scopus, Global Health, Web of Science, and PubMed Central, Indian Journal of Transplantation and Google Scholar. TIME PERIOD: 1 January 1994 to 31 December 2021. PARTICIPANTS: Individuals of Indian origin living globally. RESULTS: Eighty-nine studies were included with more than 29 000 participants and quality of the studies were assessed using Joanna Briggs Institute's critical appraisal tool. Though majority of the participants had knowledge toward organ donation with a positive influence on willingness, the gap between knowledge and willingness was huge, with minimal registration influenced by the complex sociocultural constructs. Various sociocultural constructs such as family, fear and mistrust, religion, and bodily issues play a vital role. Differences were identified in willingness to donate and register between southern and other regions of India. Indian's organ donation behaviour in other geographical locations differed based on the socioreligious background of the country they lived in such as in Malaysia, Canada and the UK. However, they were collective in decision-making and had complex sociocultural interference irrespective of the country the individual lived which differed only in their next generations. CONCLUSION: Though this study showed the complex relationship, and its influences on organ donation behaviour, lacunae were identified to further understand how such complex interactions determine or inform the behaviour. Also, methodological issues were identified, where this particular population outside India were collectively studied with their neighbouring population which are not homogenous. Studies in India majorly addressed a similar aim using similar methods which produced repetition of studies leading to lack of diversified, wider and in-depth research. Therefore, while this systematic review addressed the barriers toward organ donation among Indians living globally, it also informs various gaps in research and also methodological issues. PROSPERO REGISTRATION NUMBER: CRD42019155274.
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Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Povo Asiático , Conhecimentos, Atitudes e Prática em Saúde , Humanos , ConhecimentoRESUMO
The UK's minority ethnic population, despite being at higher risk of COVID-19 and experiencing poorer health outcomes, continue to have lower uptake of the COVID-19 vaccine compared with their white British counterparts. Given the importance of the vaccination programme in improving health outcomes, this research sought to examine the influential factors that impact the decision to accept the COVID-19 vaccination among an ethnically diverse community. A total of 1058 residents from Luton, UK, a large town with an ethnically diverse population, completed a community survey. Questions centred around uptake or individuals' intentions to accept the offer of COVID-19 vaccination alongside demographics, knowledge, and views on the vaccine. A binary logistic regression analysis was conducted to determine the most significant predictors of vaccine hesitancy, while respondents' reasons for not getting vaccinated were identified using qualitative content analysis. Findings revealed that age and ethnicity were the only sociodemographic factors to predict vaccine hesitancy. Knowledge of symptoms and transmission routes, alongside ensuring information about COVID-19 was objectively sourced, were all identified as protective factors against vaccine hesitancy. Qualitative analysis revealed that 'lack of trust in government/authorities' and 'concern of the speed of vaccine development' were the most common reasons for non-uptake. This research reinforces the importance of age, ethnicity, and knowledge as influential factors in predicting vaccine hesitancy. Further, this study uncovers some of the barriers of uptake that can be utilised in developing promotional campaigns to reduce vaccine hesitancy in certain sections of the diverse UK population.
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Background: Minority ethnic groups are at increased risk of COVID-19 related mortality or morbidity yet continue to have a disproportionally lower uptake of the vaccine. The importance of adherence to prevention and control measures to keep vulnerable populations and their families safe therefore remains crucial. This research sought to examine the knowledge, perceived risk, and attitudes toward COVID-19 among an ethnically diverse community. Methods: A cross-sectional self-administered questionnaire was implemented to survey ethnic minority participants purposefully recruited from Luton, an ethnically diverse town in the southeast of England. The questionnaire was structured to assess participants knowledge, perceived risk, attitudes toward protective measures as well as the sources of information about COVID-19. The questionnaire was administered online via Qualtrics with the link shared through social media platforms such as Facebook, Twitter, and WhatsApp. Questionnaires were also printed into brochures and disseminated via community researchers and community links to individuals alongside religious, community and outreach organisations. Data were analysed using appropriate statistical techniques, with the significance threshold for all analyses assumed at p = 0.05. Findings: 1,058 participants (634; 60% females) with a median age of 38 (IQR, 22) completed the survey. National TV and social networks were the most frequently accessed sources of COVID-19 related information; however, healthcare professionals, whilst not widely accessed, were viewed as the most trusted. Knowledge of transmission routes and perceived susceptibility were significant predictors of attitudes toward health-protective practises. Conclusion/recommendation: Improving the local information provision, including using tailored communication strategies that draw on trusted sources, including healthcare professionals, could facilitate understanding of risk and promote adherence to health-protective actions.