Single-cell dissection of the human motor and prefrontal cortices in ALS and FTLD.

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.

Temporal patterns of gut microbiota in lemurs (Eulemur rubriventer) living in intact and disturbed habitats in a novel sample type.

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.

The impact of COVID-19 on the changes in health behaviours among Black, Asian and Minority Ethnic (BAME) communities in the United Kingdom (UK): a scoping review.

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.

Improving support for breastfeeding mothers: a qualitative study on the experiences of breastfeeding among mothers who reside in a deprived and culturally diverse community.

BACKGROUND: The United Kingdom has one of the lowest breastfeeding rates in Europe, with the initiation and continuation of breastfeeding shown to be closely related to the mothers' age, ethnicity and social class. Whilst the barriers that influence a woman's decision to breastfeed are well documented, less is known how these barriers vary by the UK's diverse population. As such, this study aimed to explore mothers' experiences of breastfeeding and accessing breastfeeding services offered locally amongst a deprived and culturally diverse community. METHODS: A qualitative interpretive study comprising of 63 mothers (white British n = 8, Pakistani n = 13, Bangladeshi n = 10, black African n = 15 and Polish n = 17) who took part in single-sex focus groups, conducted in local community centres across the most deprived and ethnically diverse wards in Luton, UK. The focus groups were audio-recorded, transcribed and analysed thematically using Framework Analysis. RESULTS: The most common barriers to breastfeeding irrespective of ethnicity were perceptions surrounding pain and lack of milk. Confidence and motivation were found to be crucial facilitators of breastfeeding; whereby mothers felt that interventions should seek to reassure and support mothers not only during the early stages but throughout the breastfeeding journey. Mothers particularly valued the practical support provided by health care professions particularly surrounding positioning and attachment techniques. However, many mothers felt that the support from health care professionals was not always followed through. CONCLUSIONS: The findings presented inform important recommendations for the design and implementation of future programs and interventions targeted at reducing breastfeeding inequalities. Interventions should focus on providing mothers practical support and reassurance not only during the early stages but throughout their breastfeeding journey. The findings also highlight the need for tailoring services to support diverse communities which acknowledge different traditional and familial practices.

Parents' experiences of complementary feeding among a United Kingdom culturally diverse and deprived community.

Complementary feeding practices and adherence to health recommendations are influenced by a range of different and often interrelating factors such as socio-economic and cultural factors. However, the factors underlying these associations are often complex with less awareness of how complementary feeding approaches vary across the UK's diverse population. This paper describes a qualitative investigation undertaken in a deprived and culturally diverse community in the UK which aimed to explore parents' knowledge, beliefs and practices of complementary feeding. One hundred and ten mothers and fathers, self-identified as being White British, Pakistani, Bangladeshi, Black African/Caribbean or Polish took part in twenty-four focus group discussions, organised by age group, sex and ethnicity. The findings revealed that most parents initiated complementary feeding before the World Health Organisation (WHO) recommendation of 6 months. Early initiation was strongly influenced by breast feeding practices alongside the extent to which parents believed that their usual milk; that is, breastmilk or formula was fulfilling their infants' nutritional needs. The composition of diet and parents' approach to complementary feeding was closely aligned to traditional cultural practices; however, some contradictions were noted. The findings also acknowledge the pertinent role of the father in influencing the dietary practices of the wider household. Learning about both the common and unique cultural feeding attitudes and practices held by parents may help us to tailor healthy complementary feeding advice in the context of increasing diversity in the United Kingdom.

Access and utilisation of primary health care services comparing urban and rural areas of Riyadh Providence, Kingdom of Saudi Arabia.

BACKGROUND: The Kingdom of Saudi Arabia (KSA) has seen an increase in chronic diseases. International evidence suggests that early intervention is the best approach to reduce the burden of chronic disease. However, the limited research available suggests that health care access remains unequal, with rural populations having the poorest access to and utilisation of primary health care centres and, consequently, the poorest health outcomes. This study aimed to examine the factors influencing the access to and utilisation of primary health care centres in urban and rural areas of Riyadh province of the KSA. METHODS: A questionnaire survey was carried out to identify the barriers and enablers to accessing PHCS in rural (n = 5) and urban (n = 5) areas of Riyadh province, selected on the classification of the population density of the governorates. An adapted version of the NHS National Survey Programme was administered that included 50 questions over 11 sections that assessed a wide range of factors related to respondent's access and experience of the PHCS. A total of 935 responses were obtained with 52.9% (n = 495) from urban areas and the remaining 47.1% (n = 440) from rural areas of Riyadh province. RESULTS: This study highlights that there are high levels of satisfaction among patients among all PHCS. In relation to differences between urban and rural respondents, the findings indicated that there were significant variations in relation to: education level, monthly income, medical investigations, receiving blood tests on time, extra opening hours, distance, cleanliness and health prevention. Core barriers for rural patients related to the distance to reach PHCS, cleanliness of the PHCS, receiving health prevention and promotion services, which should serve to improve health outcomes. CONCLUSIONS: This study highlighted important differences in access to and utilisation of PHCS between urban and rural populations in Riyadh province in the KSA. These findings have implications for policy and planning of PHCCs and reducing inequalities in health care between rural and urban populations and contributing to a reduction in the chronic disease burden in Riyadh province.

Who uses NHS health checks? Investigating the impact of ethnicity and gender and method of invitation on uptake of NHS health checks.

BACKGROUND: NHS Health Checks is a national risk assessment prevention programme for all individuals aged 40-74 that reside in England. Through the systematic assessment of an individual's ten year disease risk, this programme aims to provide early identification and subsequent management of this risk. However, there is limited evidence on how socio-demographic factors impact on uptake and what influence the invitation method has on uptake to this programme. METHODS: NHS Health Check data from April 2013 to March 2014 was analysed (N = 50,485) for all 30 GP Practices in Luton, a culturally diverse town in England, UK. Data was collected for age, ethnicity, uptake (attendance and non attendance) and invitation method (letter written, verbal face-to-face, telephone). Actual usage of NHS Health Checks was determined for each ethnic group of the population and compared using Chi-square analysis. RESULTS: The overall uptake rate for Luton was 44 %, markedly lower that the set target of 50-75 %. The findings revealed a variation of uptake in relation to age, gender, level of deprivation. Ethnicity and gender variations were also found, with 'White British' 'Black Caribbean' and 'Indian' patients most likely to take up a NHS Health Check. However, patients from 'Any Other White Background' and 'Black African' were significantly less likely to uptake an NHS Health Check compared to all other ethnic groups. Ethnicity and gender differences were also noted in relation to invitation method. CONCLUSIONS: The findings revealed that different invitation methods were effective for different ethnic and gender groups. Therefore, it is suggested that established protocols of invitation are specifically designed for maximizing the response rate for each population group. Future research should now focus on uncovering the barriers to uptake in particular culturally diverse population groups to determine how public health teams can better engage with these communities.

Exploring the factors that influence the decision to adopt and engage with an integrated assistive telehealth and telecare service in Cambridgeshire, UK: a nested qualitative study of patient 'users' and 'non-users'.

BACKGROUND: There is a political drive in the UK to use assistive technologies such as telehealth and telecare as an innovative and efficient approach to healthcare delivery. However, the success of implementation of such services remains dependent on the ability to engage the wider population to adopt these services. It has been widely acknowledged that low acceptance of technology, forms a key barrier to adoption although findings been mixed. Further, it remains unclear what, if any barriers exist between patients and how these compare to those who have declined or withdrawn from using these technologies. This research aims to address this gap focusing on the UK based Cambridgeshire Community Services Assistive Telehealth and Telecare service, an integrated model of telehealth and telecare. METHODS: Qualitative semi-structured interviews were conducted between 1st February 2014 and 1st December 2014, to explore the views and experiences of 'users' and 'non-users' using this service. 'Users' were defined as patients who used the service (N = 28) with 'non-users' defined as either referred patients who had declined the service before allocation (N = 3) or had withdrawn after using the ATT service (N = 9). Data were analysed using the Framework Method. RESULTS: This study revealed that there are a range of barriers and facilitators that impact on the decision to adopt and continue to engage with this type of service. Having a positive attitude and a perceived need that could be met by the ATT equipment were influential factors in the decision to adopt and engage in using the service. Engagement of the service centred on 'usability', 'usefulness of equipment', and 'threat to identity and independence'. CONCLUSIONS: The paper described the influential role of referrers in decision-making and the need to engage with such agencies on a strategic level. The findings also revealed that reassurance from the onset was paramount to continued engagement, particularly in older patients who appeared to have more negative feelings towards technology. In addition, there is a clear need for continued product development and innovation to not only increase usability and functionality of equipment but also to motivate other sections of the population who could benefit from such services. Uncovering these factors has important policy implications in how services can improve access and patient support through the application of assistive technology which could in turn reduce unnecessary cost and burden on overstretched health services.

Muscle atrophy and metal-on-metal hip implants: a serial MRI study of 74 hips.

BACKGROUND AND PURPOSE: Muscle atrophy is seen in patients with metal-on-metal (MOM) hip implants, probably because of inflammatory destruction of the musculo-tendon junction. However, like pseudotumors, it is unclear when atrophy occurs and whether it progresses with time. Our objective was to determine whether muscle atrophy associated with MOM hip implants progresses with time. PATIENTS AND METHODS: We retrospectively reviewed 74 hips in 56 patients (32 of them women) using serial MRI. Median age was 59 (23-83) years. The median time post-implantation was 83 (35-142) months, and the median interval between scans was 11 months. Hip muscles were scored using the Pfirrmann system. The mean scores for muscle atrophy were compared between the first and second MRI scans. Blood cobalt and chromium concentrations were determined. RESULTS: The median blood cobalt was 6.84 (0.24-90) ppb and median chromium level was 4.42 (0.20-45) ppb. The median Oxford hip score was 34 (5-48). The change in the gluteus minimus mean atrophy score between first and second MRI was 0.12 (p = 0.002). Mean change in the gluteus medius posterior portion (unaffected by surgical approach) was 0.08 (p = 0.01) and mean change in the inferior portion was 0.10 (p = 0.05). Mean pseudotumor grade increased by 0.18 (p = 0.02). INTERPRETATION: Worsening muscle atrophy and worsening pseudotumor grade occur over a 1-year period in a substantial proportion of patients with MOM hip implants. Serial MRI helps to identify those patients who are at risk of developing worsening soft-tissue pathology. These patients should be considered for revision surgery before irreversible muscle destruction occurs.

Who uses NHS Direct? Investigating the impact of ethnicity on the uptake of telephone based healthcare.

INTRODUCTION: NHS Direct, a leading telephone healthcare provider worldwide, provided 24/7 health care advice and information to the public in England and Wales (1998-2014). The fundamental aim of this service was to increase accessibility, however, research has suggested a disparity in the utilisation of this service related to ethnicity. This research presents the first national study to determine how the diverse population in England have engaged with this service. METHODS: NHS Direct call data from the combined months of July, 2010 October, 2010, January 2011 and April, 2011 was analysed (N = 1,342, 245) for all 0845 4647 NHS Direct core service calls in England. Expected usage of NHS Direct was determined for each ethnic group of the population by age and gender and compared by actual usage using Chi-square analysis. A one-way analysis of variance (ANOVA) was used to determine variations of uptake by ethnic group and Index for Multiple Deprivation (IMD) 2010 rank. RESULTS: Results confirmed that all mixed ethnic groups (White and Black Caribbean, White and Black African, White and Asian) had a higher than expected uptake of NHS Direct which held consistent across all age groups. Lower than expected uptake was found for Black (African/Caribbean) and Asian (Bangladeshi/Indian/Chinese) ethnic group which held consistent by age and gender. For the Pakistani ethnic group usage was higher than expected in adults aged 40 years and older although was lower than expected in younger age groups (0-39). CONCLUSION: Findings support previous research suggesting a variation in usage of NHS Direct influenced by ethnicity, which is evidenced on a national level. Further research is now required to examine the underlying barriers that contribute to the ethnic variation in uptake of this service.

Barriers and facilitators to using NHS Direct: a qualitative study of 'users' and 'non-users'.

BACKGROUND: NHS Direct, introduced in 1998, has provided 24/7 telephone-based healthcare advice and information to the public in England and Wales. National studies have suggested variation in the uptake of this service amongst the UK's diverse population. This study provides the first exploration of the barriers and facilitators that impact upon the uptake of this service from the perspectives of both 'users' and 'non- users'. METHODS: Focus groups were held with NHS Direct 'users' (N = 2) from Bedfordshire alongside 'non-users' from Manchester (N = 3) and Mendip, Somerset (N = 4). Each focus group had between five to eight participants. A total of eighty one people aged between 21 and 94 years old (M: 58.90, SD: 22.70) took part in this research. Each focus group discussion lasted approximately 90 minutes and was audiotape-recorded with participants' permission. The recordings were transcribed verbatim. A framework approach was used to analyse the transcripts. RESULTS: The findings from this research uncovered a range of barriers and facilitators that impact upon the uptake of NHS Direct. 'Non-users' were unaware of the range of services that NHS Direct provided. Furthermore, 'non-users' highlighted a preference for face-to face communication, identifying a lack of confidence in discussing healthcare over the telephone. This was particularly evident among older people with cognitive difficulties. The cost to telephone a '0845' number from a mobile was also viewed to be a barrier to access NHS Direct, expressed more often by 'non-users' from deprived communities. NHS Direct 'users' identified that awareness, ease of use and convenience were facilitators which influenced their decision to use the service. CONCLUSIONS: An understanding of the barriers and facilitators which impact on the access and uptake of telephone-based healthcare is essential to move patients towards the self-care model. This research has highlighted the need for telephone-based healthcare services to increase public awareness; through the delivery of more targeted advertising to promote the service provision available.

Enhancing Pragmatic Language skills for Young children with Social communication difficulties (E-PLAYS-2) trial: study protocol for a cluster-randomised controlled trial evaluating a computerised intervention to promote communicative development and collaborative skills in young children.

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.

Gender Disparities in Academic Otolaryngology.

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.

Multidisciplinary Management Strategies for Long COVID: A Narrative Review.

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.

Clinicopathologic Heterogeneity and Glial Activation Patterns in Alzheimer Disease.

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.

'A team around the child' professionals' experiences of unmet needs, access and expectations in children's palliative care services, a phenomenological study in the UK.

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.

Barriers and facilitators of deceased organ donation among Muslims living globally: protocol for an integrative systematic review using narrative synthesis.

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.

Divergent single cell transcriptome and epigenome alterations in ALS and FTD patients with C9orf72 mutation.

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.

A U.K. case study of who uses NHS direct: investigating the impact of age, gender, and deprivation on the utilization of NHS direct.

OBJECTIVES: National Health Service (NHS) Direct provides a 24/7 telephone-based healthcare advice and information service to the public in England. Locally based studies have suggested variation in the uptake of this service among the United Kingdom's diverse population. This study seeks to examine this issue at a national level. SUBJECTS AND METHODS: One month's period of national data was collected (July 2010) from the NHS Direct Clinical Assessment System for all 0845 4647 calls in England. Calls were matched to place of residence and were analyzed for age, gender, and deprivation using negative binominal regression. RESULTS: Within the context of NHS Direct the pattern of calls was highest for children 5 years old and under, with lowest call rates found for males and older people (65+ years old). Furthermore, call rates were lowest in the most deprived areas for children (0-15 years old). Gender differences were noted, whereby male call rates were higher in the most deprived areas for all age groups. Furthermore, call rates for or on behalf of older females (60+ years old) were lower in areas of extreme deprivation. CONCLUSIONS: The findings suggest there is variation in usage of NHS Direct. Such usage appears to be influenced by age, gender, and deprivation. Further research is required to examine the underlying factors that contribute to variation in uptake of these services. This will enable the development of future promotional campaigns that can target particular sections of the population to encourage use of telephone-based health services.

Barriers towards deceased organ donation among Indians living globally: an integrative systematic review using narrative synthesis.

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.