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1.
Br J Gen Pract ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950944

ABSTRACT

BACKGROUND: Routine primary care data may be a valuable resource for preconception health research and informing provision of preconception care. AIM: To review how primary care data could provide information on the prevalence of preconception indicators and examine associations with maternal and offspring health outcomes. DESIGN AND SETTING: Systematic review of observational studies using UK routine primary care data. METHOD: Literature searches were conducted in five databases (March 2023) to identify observational studies that used national primary care data from individuals aged 15-49 years. Preconception indicators were defined as medical, behavioural and social factors that may impact future pregnancies. Health outcomes included those that may occur during and after pregnancy. Screening, data extraction and quality assessment were conducted by two reviewers. RESULTS: From 5,259 records screened, 42 articles were included. The prevalence of 30 preconception indicators was described for female patients, ranging from 0.01% for sickle cell disease to >20% for each of advanced maternal age, previous caesarean section (among those with a recorded pregnancy), overweight, obesity, smoking, depression and anxiety (irrespective of pregnancy). Few studies reported indicators for male patients (n=3) or associations with outcomes (n=5). Most studies had low risk of bias, but missing data may limit generalisability. CONCLUSION: Findings demonstrate that routinely collected UK primary care data can be used to identify patients preconception care needs. Linking primary care data with health outcomes collected in other datasets is underutilised but could help quantify how optimising preconception health and care can reduce adverse outcomes for mothers and children.

2.
Addict Sci Clin Pract ; 19(1): 55, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39039560

ABSTRACT

BACKGROUND: In the U.S. there are significant racial and gender disparities in the uptake of pre-exposure prophylaxis (PrEP). Black Americans represented 14% of PrEP users in 2022, but accounted for 42% of new HIV diagnoses in 2021 and in the South, Black people represented 48% of new HIV diagnoses in 2021 but only 21% of PrEP users in 2022. Women who use drugs may be even less likely than women who do not use drugs have initiated PrEP. Moreover, women involved in community supervision programs (CSP) are less likely to initiate or use PrEP, More PrEP interventions that focus on Black women with recent history of drug use in CSPs are needed to reduce inequities in PrEP uptake. METHODS: We conducted a secondary analysis from a randomized clinical trial with a sub-sample (n = 336) of the total (N = 352) participants from the parent study (E-WORTH), who tested HIV negative at baseline were considered PrEP-eligible. Black women were recruited from CSPs in New York City (NYC), with recent substance use. Participants were randomized to either E-WORTH (n = 172) an HIV testing plus, receive a 5-session, culturally-tailored, group-based HIV prevention intervention, versus an HIV testing control group (n = 180). The 5 sessions included an introduction to PrEP and access. This paper reports outcomes on improved awareness of PrEP, willingness to use PrEP, and PrEP uptake over the 12-month follow-up period. HIV outcomes are reported in a previous paper. RESULTS: Compared to control participants, participants in this study assigned to E-WORTH had significantly greater odds of being aware of PrEP as a biomedical HIV prevention strategy (OR = 3.25, 95% CI = 1.64-6.46, p = 0.001), and indicated a greater willingness to use PrEP as an HIV prevention method (b = 0.19, 95% CI = 0.06-0.32, p = 0.004) over the entire 12-month follow-up period. CONCLUSIONS: These findings underscore the effectiveness of a culturally-tailored intervention for Black women in CSP settings in increasing awareness, and intention to initiate PrEP. Low uptake of PrEP in both arms highlight the need for providing more robust PrEP-on-demand strategies that are integrated into other services such as substance abuse treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02391233 .


Subject(s)
Black or African American , HIV Infections , Pre-Exposure Prophylaxis , Humans , Female , HIV Infections/prevention & control , HIV Infections/ethnology , Adult , New York City , Middle Aged , Substance-Related Disorders/ethnology , Substance-Related Disorders/prevention & control , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Culturally Competent Care , Young Adult , Health Knowledge, Attitudes, Practice
4.
J Infect Dis ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008379

ABSTRACT

BACKGROUND: Streptococcus pyogenes-related skin infections are increasingly implicated in the development of rheumatic heart disease (RHD) in lower-resourced settings, where they are often associated with scabies. The true prevalence of S. pyogenes-related pyoderma may be underestimated by bacterial culture. METHODS: A multiplex qPCR for S. pyogenes, Staphylococcus aureus and Sarcoptes scabiei was applied to 250 pyoderma swabs from a cross-sectional study of children <5 years in The Gambia. Direct PCR-based emm-typing was used to supplement previous whole genome sequencing (WGS) of cultured isolates. RESULTS: Pyoderma lesions with S. pyogenes increased from 51% (127/250) using culture to 80% (199/250) with qPCR. Compared to qPCR, the sensitivity of culture was 95.4% for S. pyogenes (95% CI 77.2-99.9) in samples with S. pyogenes alone (22/250, 9%), but 59.9% (95% CI 52.3-67.2) for samples with S. aureus co-infection (177/250, 71%). Direct PCR-based emm-typing was successful in 50% (46/92) of cases, identifying 27 emm-types, including six not identified by WGS (total 52 emm-types). CONCLUSIONS: Bacterial culture significantly underestimates the burden of S. pyogenes in pyoderma, particularly when co-infected with S. aureus. Molecular methods should be used to enhance the detection of S. pyogenes in surveillance studies and clinical trials of preventative measures in RHD-endemic settings.

5.
Cult Health Sex ; : 1-16, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38915232

ABSTRACT

Black women in the USA experience some of the poorest health outcomes and this is especially true for those involved in the carceral system who are at elevated risks for HIV/STIs, reproductive health, and chronic diseases. This study aimed to investigate Black women's experience accessing healthcare services. We conducted semi-structured interviews with 43 women from Project EWORTH under community supervision in New York City. We analysed responses focusing on barriers to healthcare engagement. All interviews were recorded, and data analysis was conducted using NVivo. Themes influencing Black women's ability to engage with healthcare providers and systems included: 1) disclosed provider mistrust/judgement; 2) feeling disrespected by providers and the medical system; 3) mistrust of medical providers/system/hospital/government; 4) lack of health communication; 5) low health literacy; 6) provider gender preference. Findings highlight the need to improve trust and collaboration between healthcare providers and Black women. This study addresses the critical gap in understanding perceptions of discrimination, stigma, and barriers to attaining health care. Funders and accreditation agencies must hold providers and organisations accountable for acquiring and making available diversity, equity and inclusion training for providers, demonstrating increasingly equitable medical relationships through responsiveness to patient feedback, and increasing the number of Black providers.

6.
Int J Behav Nutr Phys Act ; 21(1): 63, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867226

ABSTRACT

BACKGROUND: Islamic leaders, staff, and Muslim parents in the UK are supportive of healthy lifestyle intervention delivery through Islamic Religious Settings. Such interventions are necessary given high obesity rates in British South Asian (40%) compared to White British (32%) children of equivalent age. Co-production can facilitate the development of culturally appropriate health interventions, however it can be theoretically and practically challenging, and evaluation of co-production within an Islamic Religious Setting context is lacking. The aim of this study was to examine the feasibility and acceptability of taking a co-production approach to develop an obesity-prevention toolkit for Islamic Religious Settings. METHODS: An obesity-prevention toolkit for use in Islamic Religious Settings, incorporating physical activity, healthy diet, and organisational change, has been co-produced to be evidence-informed and contextually relevant. A qualitative process evaluation was employed to examine experiences of co-production. Semi-structured interviews (n = 15) and a focus group (n = 5) were conducted with toolkit co-production stakeholders, e.g., subject experts, an Islamic scholar, and Islamic Religious Setting staff. Transcripts were analysed inductively using reflexive thematic analysis. RESULTS: The analysis revealed four major themes regarding stakeholders' experiences of co-producing a childhood obesity-prevention toolkit for Islamic Religious Settings. These themes are: (1) attitudes towards obesity-prevention through Islamic Religious Settings, (2) benefits of co-production including capacity building and ownership (3) negotiating involvement, power, and perspectives within the co-production process, and (4) the complexities of effective communication in co-production. CONCLUSION: This study adds to the evidence-base in support of delivering health promotion through faith settings. Taking a co-production approach to develop an obesity-prevention toolkit for Islamic Religious Settings provided benefit to the toolkit product and local stakeholders. The toolkit is currently being implemented across Bradford, UK and there is potential to adapt the toolkit to other geographical contexts, and for evaluating effectiveness for preventing obesity in British Muslim families.


Subject(s)
Health Promotion , Islam , Qualitative Research , Humans , Health Promotion/methods , Female , Male , Focus Groups , Obesity/prevention & control , United Kingdom , Exercise , Pediatric Obesity/prevention & control , Adult , Child , Diet, Healthy/methods
7.
Am Heart J ; 275: 151-162, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38862074

ABSTRACT

BACKGROUND: Cardiovascular health literacy (CVHL) and social determinants of health (SDoH) play interconnected and critical roles in shaping cardiovascular health (CVH) outcomes. However, awareness of CVH risk has declined markedly, from 65% of women being aware that cardiovascular disease (CVD) is the leading cause of death for women in 2009 to just 44% being aware in 2019. The American Heart Association Research Goes Red (RGR) initiative seeks to develop an open-source, longitudinal, dynamic registry that will help women to be aware of and participate in research studies, and to learn about CVD prevention. We proposed to leverage this platform, particularly among Black and Hispanic women of reproductive age, to address CVHL gaps and advance health equity. METHODS: The primary objective of the study is to evaluate the cross-sectional association of CVHL, SDoH using a polysocial score, and CVH in women of reproductive age at increased risk of developing hypertension (HTN). To achieve this we will use a cross-sectional study design, that engages women already enrolled in the RGR registry (registry-enrolled). To enhance the racial and ethnic/social economic diversity of the cohort, we will additionally enroll 300 women from the Baltimore and Washington D.C. community into the Social Determinants of the Risk of Hypertension in Women of Reproductive Age (SAFE HEART) Study. Community-enrolled and registry-enrolled women will undergo baseline social phenotyping including detailed SDoH questionnaire, CVH metrics assessment, and CVHL assessment. The secondary objective is to assess whether a 4-month active health education intervention will result in a change in CVHL in the 300 community-enrolled women. DISCUSSION: The SAFE HEART study examines the association between CVHL, SDoH, and CVH, with a focus on racial and ethnic minority groups and socioeconomically disadvantaged women of reproductive age, and the ability to improve these parameters by an educational intervention. These findings will inform the future development of community-engaged strategies that address CVHL and SDoH among women of reproductive age.

8.
Article in English | MEDLINE | ID: mdl-38832251

ABSTRACT

INTRODUCTION: Unplanned pregnancies are associated with increased risks. Despite this, they are currently not routinely detected during antenatal care. This study evaluates the implementation of the London Measure of Unplanned Pregnancy (LMUP) - a validated measure of pregnancy planning - into antenatal care at University College London Hospital, Homerton Hospital, and St Thomas' Hospital, England, 2019-2023. METHODS: We conducted a mixed methods evaluation of the pilot. Uptake and acceptability were measured using anonymized data with non-completion of the LMUP as a proxy measure of acceptability overall. We conducted focus groups with midwives, and one-to-one interviews with women, to explore their thoughts of asking, or being asked the LMUP, which we analyzed with a Framework Analysis. RESULTS: Asking the LMUP at antenatal appointments is feasible and acceptable to women and midwives, and the LMUP performed as expected. Advantages of asking the LMUP, highlighted by participants, include providing additional support and personalizing care. Midwives' concerns about judgment were unsubstantiated; women with unplanned pregnancies valued such discussions. CONCLUSIONS: These findings support the implementation of the LMUP in routine antenatal care and show how it can provide valuable insights into the circumstances of women's pregnancies. This can be used to help midwives personalize care, and potentially reduce adverse outcomes and subsequent unplanned pregnancy. Integration of the LMUP into the Maternity Services Data Set will establish national data collection of a validated measure of unplanned pregnancy and enable analysis of the prevalence, factors, and implications of unplanned pregnancies across subpopulations and over time to inform implementation.

9.
Adv Radiat Oncol ; 9(7): 101504, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38846487

ABSTRACT

Purpose: Recruiting prospective physicians to radiation oncology can be challenging, because of limited familiarity with the field. The Assistant Clinical Research Coordinator (ACRC) program can help provide trainees early exposure to radiation oncology. Methods and Materials: The ACRC program involves hiring a college graduate to provide administrative and research support for faculty members. The program was developed with our institution's clinical trials office, which provided guidance on regulatory compliance and training. A structured selection process identifies top candidates, and a rigorous onboarding process ensures smooth transitions between ACRCs. We report characteristics and outcomes of ACRC employees and surveyed them to assess their program experience using a Likert scale. Results: From 2005 to 2023, the ACRC program paired 73 ACRCs with faculty. Most faculty (68%) are currently supported by ACRCs. In 2023, 113 applications were received for 4 positions. ACRCs have contributed to research publications (293 as coauthors and 43 as first authors) and taken on leadership roles in the department. Most program alumni have attended medical school (34 of 64 program graduates; 53%). Eight have chosen to specialize in radiation oncology (13%; 2 applying into radiation oncology, 1 in residency, and 5 attendings). Of the 25% of alumni who responded to our survey, 77% responded that the mentorship provided by the ACRC program was very or extremely effective in guiding their academic development. All respondents rated the research opportunities as good or excellent, and 77% rated the clinical experience opportunities as good or excellent. Most (77%) reported that the ACRC program had substantial or significant influence on their choice of career path. Conclusions: The ACRC program provides an opportunity to address recruitment challenges in radiation oncology by offering early exposure to the field, clinical research skills, and mentorship. With the strong interest in our job posting this year, there is potential to expand this program to other institutions.

10.
Sci Rep ; 14(1): 10947, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38740811

ABSTRACT

The immunomodulatory effects of omega-3 and omega-6 fatty acids are a crucial subject of investigation for sustainable fish aquaculture, as fish oil is increasingly replaced by terrestrial vegetable oils in aquafeeds. Unlike previous research focusing on fish oil replacement with vegetable alternatives, our study explored how the omega-6 to omega-3 polyunsaturated fatty acid (PUFA) ratio in low-fish oil aquafeeds influences Atlantic salmon's antiviral and antibacterial immune responses. Atlantic salmon were fed aquafeeds rich in soy oil (high in omega-6) or linseed oil (high in omega-3) for 12 weeks and then challenged with bacterial (formalin-killed Aeromonas salmonicida) or viral-like (polyriboinosinic polyribocytidylic acid) antigens. The head kidneys of salmon fed high dietary omega-3 levels exhibited a more anti-inflammatory fatty acid profile and a restrained induction of pro-inflammatory and neutrophil-related genes during the immune challenges. The high-omega-3 diet also promoted a higher expression of genes associated with the interferon-mediated signaling pathway, potentially enhancing antiviral immunity. This research highlights the capacity of vegetable oils with different omega-6 to omega-3 PUFA ratios to modulate specific components of fish immune responses, offering insights for future research on the intricate lipid nutrition-immunity interplay and the development of novel sustainable low-fish oil clinical aquaculture feeds.


Subject(s)
Aeromonas salmonicida , Fatty Acids, Omega-3 , Fatty Acids, Omega-6 , Fish Diseases , Salmo salar , Animals , Salmo salar/immunology , Fatty Acids, Omega-6/pharmacology , Fatty Acids, Omega-3/pharmacology , Aeromonas salmonicida/immunology , Fish Diseases/immunology , Fish Diseases/prevention & control , Fish Diseases/virology , Head Kidney/immunology , Animal Feed , Soybean Oil/pharmacology , Fish Oils/pharmacology , Aquaculture/methods
11.
Dev Comp Immunol ; 156: 105165, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38499166

ABSTRACT

Renibacterium salmoninarum causes Bacterial Kidney Disease (BKD) in several fish species. Atlantic lumpfish, a cleaner fish, is susceptible to R. salmoninarum. To profile the transcriptome response of lumpfish to R. salmoninarum at early and chronic infection stages, fish were intraperitoneally injected with either a high dose of R. salmoninarum (1 × 109 cells dose-1) or PBS (control). Head kidney tissue samples were collected at 28- and 98-days post-infection (dpi) for RNA sequencing. Transcriptomic profiling identified 1971 and 139 differentially expressed genes (DEGs) in infected compared with control samples at 28 and 98 dpi, respectively. At 28 dpi, R. salmoninarum-induced genes (n = 434) mainly involved in innate and adaptive immune response-related pathways, whereas R. salmoninarum-suppressed genes (n = 1537) were largely connected to amino acid metabolism and cellular processes. Cell-mediated immunity-related genes showed dysregulation at 98 dpi. Several immune-signalling pathways were dysregulated in response to R. salmoninarum, including apoptosis, alternative complement, JAK-STAT signalling, and MHC-I dependent pathways. In summary, R. salmoninarum causes immune suppression at early infection, whereas lumpfish induce a cell-mediated immune response at chronic infection. This study provides a complete depiction of diverse immune mechanisms dysregulated by R. salmoninarum in lumpfish and opens new avenues to develop immune prophylactic tools to prevent BKD.


Subject(s)
Fish Diseases , Gene Expression Profiling , Head Kidney , Immunity, Innate , Renibacterium , Transcriptome , Animals , Head Kidney/immunology , Fish Diseases/immunology , Fish Diseases/microbiology , Renibacterium/immunology , Renibacterium/genetics , Immunity, Innate/genetics , Fish Proteins/genetics , Fish Proteins/metabolism , Adaptive Immunity/genetics , Fishes/immunology , Fishes/microbiology , Chronic Disease , Perciformes/immunology , Perciformes/microbiology , Gram-Negative Bacterial Infections/immunology , Kidney Diseases/immunology , Kidney Diseases/microbiology , Kidney Diseases/genetics , Kidney Diseases/veterinary , Micrococcaceae/genetics , Micrococcaceae/immunology
12.
Dev Comp Immunol ; 156: 105161, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38521379

ABSTRACT

Low-oxygen levels (hypoxia) in aquatic habitats are becoming more common because of global warming and eutrophication. However, the effects on the health/disease status of fishes, the world's largest group of vertebrates, are unclear. Therefore, we assessed how long-term hypoxia affected the immune function of sablefish, an ecologically and economically important North Pacific species, including the response to a formalin-killed Aeromonas salmonicida bacterin. Sablefish were held at normoxia or hypoxia (100% or 40% air saturated seawater, respectively) for 6-16 weeks, while we measured a diverse array of immunological traits. Given that the sablefish is a non-model organism, this involved the development of a species-specific methodological toolbox comprised of qPCR primers for 16 key immune genes, assays for blood antibacterial defences, the assessment of blood immunoglobulin (IgM) levels with ELISA, and flow cytometry and confocal microscopy techniques. We show that innate immune parameters were typically elevated in response to the bacterial antigens, but were not substantially affected by hypoxia. In contrast, hypoxia completely prevented the ∼1.5-fold increase in blood IgM level that was observed under normoxic conditions following bacterin exposure, implying a serious impairment of adaptive immunity. Since the sablefish is naturally hypoxia tolerant, our results demonstrate that climate change-related deoxygenation may be a serious threat to the immune competency of fishes.


Subject(s)
Adaptive Immunity , Aeromonas salmonicida , Climate Change , Fish Diseases , Animals , Aeromonas salmonicida/immunology , Aeromonas salmonicida/physiology , Fish Diseases/immunology , Fish Diseases/microbiology , Hypoxia/immunology , Immunity, Innate , Immunoglobulin M/blood , Immunoglobulin M/immunology , Fishes/immunology , Fishes/microbiology , Oxygen/metabolism , Gram-Negative Bacterial Infections/immunology , Antigens, Bacterial/immunology
13.
Circulation ; 149(14): e1028-e1050, 2024 04 02.
Article in English | MEDLINE | ID: mdl-38415358

ABSTRACT

A major focus of academia, industry, and global governmental agencies is to develop and apply artificial intelligence and other advanced analytical tools to transform health care delivery. The American Heart Association supports the creation of tools and services that would further the science and practice of precision medicine by enabling more precise approaches to cardiovascular and stroke research, prevention, and care of individuals and populations. Nevertheless, several challenges exist, and few artificial intelligence tools have been shown to improve cardiovascular and stroke care sufficiently to be widely adopted. This scientific statement outlines the current state of the art on the use of artificial intelligence algorithms and data science in the diagnosis, classification, and treatment of cardiovascular disease. It also sets out to advance this mission, focusing on how digital tools and, in particular, artificial intelligence may provide clinical and mechanistic insights, address bias in clinical studies, and facilitate education and implementation science to improve cardiovascular and stroke outcomes. Last, a key objective of this scientific statement is to further the field by identifying best practices, gaps, and challenges for interested stakeholders.


Subject(s)
Cardiovascular Diseases , Heart Diseases , Stroke , United States , Humans , Artificial Intelligence , American Heart Association , Cardiovascular Diseases/therapy , Cardiovascular Diseases/prevention & control , Stroke/diagnosis , Stroke/prevention & control
14.
BMJ Open ; 14(1): e079155, 2024 01 18.
Article in English | MEDLINE | ID: mdl-38238045

ABSTRACT

INTRODUCTION: High-quality shared decision-making (SDM) is a priority of health services, but only achieved in a minority of surgical consultations. Improving SDM for surgical patients may lead to more effective care and moderate the impact of treatment consequences. There is a need to establish effective ways to achieve sustained and large-scale improvements in SDM for all patients whatever their background. The ALPACA Study aims to develop, pilot and evaluate a decision support intervention that uses real-time feedback of patients' experience of SDM to change patients' and healthcare professionals' decision-making processes before adult elective surgery and to improve patient and health service outcomes. METHODS AND ANALYSIS: This protocol outlines a mixed-methods study, involving diverse stakeholders (adult patients, healthcare professionals, members of the community) and three National Health Service (NHS) trusts in England. Detailed methods for the assessment of the feasibility, usability and stakeholder views of implementing a novel system to monitor the SDM process for surgery automatically and in real time are described. The study will measure the SDM process using validated instruments (CollaboRATE, SDM-Q-9, SHARED-Q10) and will conduct semi-structured interviews and focus groups to examine (1) the feasibility of automated data collection, (2) the usability of the novel system and (3) the views of diverse stakeholders to inform the use of the system to improve SDM. Future phases of this work will complete the development and evaluation of the intervention. ETHICS AND DISSEMINATION: Ethical approval was granted by the NHS Health Research Authority North West-Liverpool Central Research Ethics Committee (reference: 21/PR/0345). Approval was also granted by North Bristol NHS Trust to undertake quality improvement work (reference: Q80008) overseen by the Consent and SDM Programme Board and reporting to an Executive Assurance Committee. TRIAL REGISTRATION NUMBER: ISRCTN17951423; Pre-results.


Subject(s)
Camelids, New World , Decision Making , Adult , Animals , Humans , State Medicine , Feedback , Patient Participation
15.
Hum Gene Ther ; 35(13-14): 506-516, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38264994

ABSTRACT

Adeno-associated virus (AAV)-based gene therapies have shown promise as novel treatments for rare genetic disorders such as hemophilia A and spinal muscular atrophy. However, cellular immune responses mediated by cytotoxic (CD8+) and helper (CD4+) T cells may target vector-transduced cells as well as healthy immune cells, impacting safety and efficacy. In this study, we describe the optimization and reproducibility of interferon-γ (IFNγ)-based and interleukin-2 (IL-2)-based enzyme-linked immunosorbent spot (ELISpot) assays for measuring T cell responses against AAV peptide antigens. For method optimization, peripheral blood mononuclear cells (PBMCs) were isolated from healthy human donors and stimulated with commercially available major histocompatibility complex (MHC) class I or II-specific peptides as positive controls. Peptide pools were designed from published AAV8 and AAV9 capsid protein sequences and then used to assess the presence of AAV-specific T cell responses. Our results demonstrate a measurable increase in IFNγ and IL-2-producing cells after AAV peptide presentation. Furthermore, there was an observed difference in the magnitude and specificity of response to peptide pools based on AAV serotype and donor. Finally, using individual peptides, we identified a region of the AAV9 capsid protein that can elicit an immunogenic response. This work shows the applicability of ELISpot in assessing anti-AAV immune responses and provides insight into how novel recombinant AAV vectors could be designed to reduce immunogenic potential.


Subject(s)
Dependovirus , Enzyme-Linked Immunospot Assay , Genetic Vectors , Interferon-gamma , Interleukin-2 , Peptides , Dependovirus/genetics , Dependovirus/immunology , Humans , Enzyme-Linked Immunospot Assay/methods , Genetic Vectors/genetics , Interferon-gamma/metabolism , Interferon-gamma/immunology , Peptides/immunology , Interleukin-2/immunology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Genetic Therapy , Capsid Proteins/immunology , Capsid Proteins/genetics , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
16.
Gene ; 894: 147984, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-37952747

ABSTRACT

Atlantic salmon (Salmo salar) are not only the world's most economically important farmed fish in terms of total value, but also a salmonid, which means that they are invaluable for studies of the evolutionary fate of genes following multiple whole-genome duplication (WGD) events. In this study, four paralogues of the molecular chaperone serpinh1 were characterized in Atlantic salmon, as while this gene is considered to be a sensitive biomarker of heat stress in salmonids, mammalian studies have also identified it as being essential for collagen structural assembly and integrity. The four salmon paralogues were cloned and sequenced so that in silico analyses at the nucleotide and deduced amino acid levels could be performed. In addition, qPCR was used to measure: paralogue- and sex-specific constitutive serpinh1 expression across 17 adult tissues; and their expression in the liver and head kidney of male Atlantic salmon as affected by stress phenotype (high vs. low responder), increased temperature, and injection with a multi-valent vaccine. Compared to the other three paralogues, serpinh1a-2 had a unique constitutive expression profile across the 17 tissues. Although stress phenotype had minimal impact on the transcript expression of the four paralogues, injection with a commercial vaccine containing several formalin inactivated bacterins increased the expression of most paralogues (by 1.1 to 4.5-fold) across both tissues. At 20 °C, the expression levels of serpinh1a-1 and serpinh1a-2 were generally lower (by -1.1- to -1.6-fold), and serpinh1b-1 and serpinh1b-2 were 10.2- to 19.0-fold greater, in comparison to salmon held at 12 °C. With recent studies suggesting a putative link between serpinh1 and upper thermal tolerance in salmonids, the current research is a valuable first step in elucidating the potential mechanisms involved. This research: supports the use of serpinh1b-1 and serpinh1b-2 as a biomarkers of heat stress in salmon; and provides evidence of neo- and/or subfunctionalization between the paralogues, and important insights into how multiple genome duplication events can potentially lead to evolutionary divergence.


Subject(s)
Salmo salar , Vaccines , Animals , Female , Male , Salmo salar/genetics , Genome , Biological Evolution , Gene Expression Profiling , Mammals
17.
Soc Work Health Care ; 63(1): 35-52, 2024.
Article in English | MEDLINE | ID: mdl-37965711

ABSTRACT

This study examined retention and its relationship to mental health, substance use, and social determinants of health in a randomized clinical trial of a behavioral HIV/sexually transmitted infection prevention intervention with drug-involved Black women (N = 348) under community supervision programs in New York City. Using secondary analysis, we used logistic models to test the association between factors related to mental health, substance use, and social determinants of health and follow-up assessment completion (three, six, and 12 months). Participants who were diagnosed with schizophrenia had lower odds of retention. Participants who misused prescription opiates during their lifetime or food insecure in the past 90 days had higher odds of retention throughout the intervention.


Subject(s)
HIV Infections , Sexually Transmitted Diseases , Substance-Related Disorders , Humans , Female , HIV Infections/diagnosis , Sexually Transmitted Diseases/prevention & control , Substance-Related Disorders/diagnosis , Mental Health , Delivery of Health Care
18.
JACC Heart Fail ; 12(3): 508-520, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38099890

ABSTRACT

BACKGROUND: Individuals with acute decompensated heart failure (ADHF) have a varying response to diuretic therapy. Strategies for the early identification of low diuretic efficiency to inform decongestion therapies are lacking. OBJECTIVES: The authors sought to develop and externally validate a machine learning-based phenomapping approach and integer-based diuresis score to identify patients with low diuretic efficiency. METHODS: Participants with ADHF from ROSE-AHF, CARRESS-HF, and ATHENA-HF were pooled in the derivation cohort (n = 794). Multivariable finite-mixture model-based phenomapping was performed to identify phenogroups based on diuretic efficiency (urine output over the first 72 hours per total intravenous furosemide equivalent loop diuretic dose). Phenogroups were externally validated in other pooled ADHF trials (DOSE/ESCAPE). An integer-based diuresis score (BAN-ADHF score: blood urea nitrogen, creatinine, natriuretic peptide levels, atrial fibrillation, diastolic blood pressure, hypertension and home diuretic, and heart failure hospitalization) was developed and validated based on predictors of the diuretic efficiency phenogroups to estimate the probability of low diuretic efficiency using the pooled ADHF trials described earlier. The associations of the BAN-ADHF score with markers and symptoms of congestion, length of stay, in-hospital mortality, and global well-being were assessed using adjusted regression models. RESULTS: Clustering identified 3 phenogroups based on diuretic efficiency: phenogroup 1 (n = 370; 47%) had lower diuretic efficiency (median: 13.1 mL/mg; Q1-Q3: 7.7-19.4 mL/mg) than phenogroups 2 (n = 290; 37%) and 3 (n = 134; 17%) (median: 17.8 mL/mg; Q1-Q3: 10.8-26.1 mL/mg and median: 35.3 mL/mg; Q1-Q3: 17.5-49.0 mL/mg, respectively) (P < 0.001). The median urine output difference in response to 80 mg intravenous twice-daily furosemide between the lowest and highest diuretic efficiency group (phenogroup 1 vs 3) was 3,520 mL/d. The BAN-ADHF score demonstrated good model performance for predicting the lowest diuretic efficiency phenogroup membership (C-index: 0.92 in DOSE/ESCAPE validation cohort) that was superior to measures of kidney function (creatinine or blood urea nitrogen), natriuretic peptide levels, or home diuretic dose (DeLong P < 0.001 for all). Net urine output in response to 80 mg intravenous twice-daily furosemide among patients with a low vs high (5 vs 20) BAN-ADHF score was 2,650 vs 660 mL per 24 hours, respectively. Participants with higher BAN-ADHF scores had significantly lower global well-being, higher natriuretic peptide levels on discharge, a longer in-hospital stay, and a higher risk of in-hospital mortality in both derivation and validation cohorts. CONCLUSIONS: The authors developed and validated a phenomapping strategy and diuresis score for individuals with ADHF and differential response to diuretic therapy, which was associated with length of stay and mortality.


Subject(s)
Diuretics , Heart Failure , Humans , Diuretics/therapeutic use , Furosemide/therapeutic use , Creatinine , Natriuretic Peptides , Acute Disease
19.
Contraception ; 131: 110359, 2024 03.
Article in English | MEDLINE | ID: mdl-38159791

ABSTRACT

OBJECTIVE: We assessed contraceptive use changes during the second lockdown due to COVID-19 in Brazil and their associated factors. STUDY DESIGN: This was a longitudinal web-based study in which 725 non-pregnant Brazilian women aged 18 to 49 completed an online structured survey about their contraceptive practices in two rounds in 2021. Multivariate multinomial logistic regression was used to analyze factors associated with contraceptive use changes during COVID-19. RESULTS: Sixty percent reported they changed their contraceptive use during COVID-19, especially starting to use a method or switching to a more effective one (32%). In adjusted analysis, women who were ambivalent about a future pregnancy were more likely to switch to a more effective method (adjusted odds ratio [aOR] 2.33, 95% CI 1.42-3.83) and to stop using contraceptive (aOR 3.64, 95% CI 1.91-6.91). Women with a partner were less likely to switch to a more effective method (aOR 0.61, 95% CI 0.39-0.93) and to stop using contraceptive (aOR 0.53, 95% CI 0.31-0.93), but more likely to switch to a less effective method (aOR 2.25, 95% CI 1.16-4.34). Age was also associated with contraceptive use changes. CONCLUSIONS: Contraceptive use among Brazilian women during COVID-19 depended on their age and partnership status. During the period of the highest peak in the number of cases and deaths in the country, ambivalence towards a future pregnancy increased changes in contraceptive use. IMPLICATIONS: Contraceptive changes were observed during a two-wave web-survey in Brazil depending on women's age and partnership status. Ambivalence towards a future pregnancy increased changes in contraceptive use and should be considered in future studies regarding sexual and reproductive health and COVID-19 as well as in family planning program implementation.


Subject(s)
COVID-19 , Contraceptive Agents , Pregnancy , Female , Humans , Brazil , Communicable Disease Control , Family Planning Services , Contraception Behavior , Internet , Contraception/methods
20.
Fam Pract ; 41(2): 131-138, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38124485

ABSTRACT

BACKGROUND: For health services to help people plan for or prevent pregnancy, health professionals need an acceptable way to identify individuals' preferences. OBJECTIVE: To assess women's views on the acceptability of specific questions about pregnancy preferences when asked by health professionals in a variety of primary care contexts. METHODS: One-to-one in-depth interviews with 13 women aged 18-48 from across the UK, involving role-play scenarios and ranking exercises. Interviews covered a range of settings and health professionals, different question wording, and ways of asking (in person or digitally). We conducted a thematic Framework Analysis, focussing on themes relating to feelings and preferences. RESULTS: Women were generally open to being asked about pregnancy preferences if they understood the rationale, it was asked in a relevant context, such as in women's health-related consultations, and there was follow-up. After signposting, an open question, such as 'How would you feel about having a baby in the next year?' was preferred in a face-to-face context as it enabled discussion. While some women valued a face-to-face discussion with a health professional, for others the privacy and convenience of a digital option was preferred; methods should be tailored to the target population. CONCLUSION: Discussion of pregnancy preferences via a range of formats is acceptable to, and valued by, women in the UK across a range of primary care settings. Acceptability to health professionals and feasibility of implementation needs further exploration and would benefit from greater public awareness of the benefits of pregnancy planning.


Subject(s)
Intention , Women's Health , Pregnancy , Female , Humans , Qualitative Research , Emotions , Primary Health Care
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