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Introduction: Brain magnetic resonance imaging (MRI) and inflammatory biomarkers are crucial for investigating preclinical neurocognitive disorders. Current investigations focus on a few inflammatory markers. The study aims to investigate the associations between inflammatory biomarkers and MRI measures and to examine sex differences among the associations in the Framingham Heart Study., Methods: Dementia and stroke-free participants underwent OLINK Proteomics profiling and MRI measurements within 5 years. Pairwise cross-sectional analysis assessed 68 biomarkers with 13 brain MRI volumes, adjusting for covariates and familial correlations., Results: Elevated CDCP1, IL6, OPG, and 4E.BP1 were related to smaller total cerebral brain volume (TCBV), whereas higher HGF, IL8, and MMP10 were associated with smaller TCBV, total and frontal white matter volumes. Higher SCF and TWEAK were associated with larger TCBV. In sex-stratified analyses, associations were observed exclusively among males., Discussion: We report several associations between inflammatory biomarkers and brain volumes, highlighting different associations within sex subgroups., Highlights: Higher CDCP1, IL6, OPG, and 4E.BP1 levels were associated with smaller TCBV. Higher levels of HGF, IL8 and MMP10 were associated with smaller TCBV, CWV and FWV. Higher levels of SCF and TWEAK, were associated with larger TCBV. Significance diminished in models adjusting for CVD risk factors. Associations were observed exclusively in males., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Most gene expression and alternative splicing quantitative trait loci (eQTL/sQTL) studies have been biased toward European ancestry individuals. Here, we performed eQTL and sQTL analyses using TOPMed whole-genome sequencing-derived genotype data and RNA-sequencing data from stored peripheral blood mononuclear cells in 1,012 African American participants from the Jackson Heart Study (JHS). At a false discovery rate of 5%, we identified 17,630 unique eQTL credible sets covering 16,538 unique genes; and 24,525 unique sQTL credible sets covering 9,605 unique genes, with lead QTL at P < 5e-8. About 24% of independent eQTLs and independent sQTLs with a minor allele frequency > 1% in JHS were rare (minor allele frequency < 0.1%), and therefore unlikely to be detected, in European ancestry individuals. Finally, we created an open database, which is freely available online, allowing fast query and bulk download of our QTL results., Competing Interests: Conflict of interest: LMR has a consulting arrangement with the TOPMed Administrative Coordinating Center (through Westat)., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Arterial stiffness measured by total pulse wave velocity (T-PWV) is associated with increased risk of multiple age-related diseases. T-PWV can be described by structural (S-PWV) and load-dependent (LD-PWV) arterial stiffening. T-cells have been associated with arterial remodeling, blood pressure, and arterial stiffness in humans and animals; however, it is unknown whether T-cells are related to S-PWV or LD-PWV. Therefore, we evaluated the cross-sectional associations of peripheral T-cell subpopulations with T-PWV, S-PWV, and LD-PWV stiffness., Methods: Peripheral blood T-cells were characterized using flow cytometry and the carotid artery was measured using B-mode ultrasound to calculate T-PWV at the baseline examination in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA, n=1,984). A participant-specific exponential model was used to calculate S-PWV and LD-PWV based on elastic modulus and blood pressure gradients. The associations between five primary (p-significance<0.01) and twenty-five exploratory (p-significance<0.05) immune cell subpopulations, per 1-SD increment, and arterial stiffness measures were assessed using adjusted, linear regressions., Results: For the primary analysis, higher CD4 + CD28 - CD57 + T-cells were associated with higher LD-PWV (β=0.04 m/s, p<0.01) after adjusting for co-variates. For the exploratory analysis, T-cell subpopulations that commonly shift with aging towards memory and differentiated/immunosenescent phenotypes were associated with greater T-PWV, S-PWV, and LD-PWV after adjusting for co-variates., Conclusions: In this cross-sectional study, several T-cell subpopulations commonly associated with aging were related with measures of arterial stiffness. Longitudinal studies that examine changes in T-cell subpopulations and measures of arterial stiffness are warranted.

Aims: Intercellular adhesion molecule-1 (ICAM-1) facilitates inflammation via leucocyte recruitment and has been implicated in heart failure with preserved ejection fraction (HFpEF). Approximately 35% of African American individuals carry a copy of an ICAM1 missense variant (rs5491; p.K56M), which is associated with an increased risk of HFpEF. The pathways by which rs5491 increases HFpEF risk are not well defined. We evaluated the circulating immune cell profile of rs5491., Methods: Among African American individuals in the Multi-Ethnic Study of Atherosclerosis, we evaluated the associations of rs5491 with 29 circulating peripheral blood mononuclear cell subsets. The top immune cells were then related to echocardiographic measures of structure and function., Results: Among 502 individuals with immune cell profiling (mean age 63 years, 51% female), 191 individuals (38%) had at least one copy of rs5491. Each additional rs5491 allele was significantly associated with higher proportions of Tc17 CD8 + cytotoxic T cells (β = 1.34, SE = 0.45, P = 9.5 × 10 -5 ) and Tc2 CD8 + cytotoxic T cells (β = 1.19, SE = 0.44, P = 0.00012). There were no other associations noted between rs5491 and the remaining immune cells. A higher proportion of Tc17 cells was significantly associated with a higher left ventricular ejection fraction, E/e' average and right ventricular systolic pressure (RVSP), while a higher proportion of Tc2 cells was significantly associated with a higher RVSP., Conclusions: The ICAM1 p.K56M variant (rs5491) carries a distinct and inflammatory T-cell subset profile. These cytotoxic T cells are in turn associated with alterations in cardiac function and adverse haemodynamics later in life, thus providing insight into pathways by which rs5491 may increase the risk of HFpEF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Global life expectancy is rising, with the 60 + age group projected to hit 2 billion by 2050. Aging impacts the immune system. A notable marker of immune system aging is the presence of Aging-Related Immune Cell Phenotypes (ARIPs). Despite their importance, links between immune cell phenotypes including ARIPs and mortality are underexplored. We prospectively investigated 16 different immune cell phenotypes using flow cytometry and IL-6 in relation to survival outcome among dementia-free Framingham Heart Study (FHS) offspring cohort participants who attended the seventh exam (1998-2001)., Results: Among 996 participants (mean age 62 years, range 40 to 88 years, 52% female), the 19-year survival rate was 65%. Adjusting for age, sex, and cytomegalovirus (CMV) serostatus, higher CD4/CD8 and Tc17/CD8 + Treg ratios were significantly associated with lower all-cause mortality (HR: 0.86 [0.76-0.96], 0.84 [0.74-0.94], respectively), while higher CD8 regulatory cell levels (CD8 + CD25 + FoxP3 +) were associated with increased all-cause mortality risk (HR = 1.17, [1.03-1.32]). Elevated IL-6 levels correlated with higher all-cause, cardiovascular, and non-cardiovascular mortality (HR = 1.43 [1.26-1.62], 1.70 [1.31-2.21], and 1.36 [1.18-1.57], respectively). However, after adjusting for cardiovascular risk factors and prevalent cancer alongside age, sex, and CMV, immune cell phenotypes were no longer associated with mortality in our cohort. Nonetheless, IL-6 remained significantly associated with all-cause and cardiovascular mortality (HRs: 1.3 [1.13-1.49], 1.5 [1.12-1.99], respectively)., Conclusions: In 19-year follow-up, higher Tc17/CD8 + Treg and CD4/CD8 ratios were associated with lower all-cause mortality, while the CD8 + CD25 + FoxP3 + (CD8 + Treg) phenotype showed increased risk. Elevated IL-6 levels consistently correlated with amplified mortality risks. These findings highlight the links between immune phenotypes and mortality, suggesting implications for future research and clinical considerations., (© 2024. The Author(s).)

Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our mCA fitness estimates, derived by aggregating per-individual PACER scores, were correlated (R 2  = 0.49) with an alternative approach that estimated fitness of mCAs in the UK Biobank using population-level distributions of clonal fraction. Among individuals with JAK2 V617F clonal hematopoiesis of indeterminate potential or mCAs affecting the JAK2 gene on chromosome 9, PACER score was strongly correlated with erythrocyte count. In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identified a TCL1A locus variant associated with mCA clonal expansion rate, with suggestive variants in NRIP1 and TERT., (© 2024. The Author(s).)

Abstract: Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10-9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.

Background: Circulating immune cells have gained interest as biomarkers of hepatic steatosis. Data on the relationships between immune cell subsets and early-stage steatosis in population-based cohorts are limited., Methods: This study included 1,944 asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA) with immune cell phenotyping and computed tomography measures of liver fat. Participants with heavy alcohol use were excluded. A liver-to-spleen ratio Hounsfield units (HU) <1.0 and liver attenuation <40 HU were used to diagnose liver fat presence and >30% liver fat content, respectively. Logistic regression estimated cross-sectional associations of immune cell subsets with liver fat parameters adjusted for risk factors. We hypothesized that higher proportions of non-classical monocytes, Th1, Th17, and memory CD4 + T cells, and lower proportions of classical monocytes and naive CD4 + T cells, were associated with liver fat. Exploratory analyses evaluated additional immune cell phenotypes (n = 19)., Results: None of the hypothesized cells were associated with presence of liver fat. Higher memory CD4 + T cells were associated with >30% liver fat content, but this was not significant after correction for multiple hypothesis testing (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.03, 1.66). In exploratory analyses unadjusted for multiple testing, higher proportions of CD8 + CD57 + T cells were associated with liver fat presence (OR: 1.21, 95% CI: 1.02, 1.44) and >30% liver fat content (OR: 1.34, 95% CI: 1.07, 1.69)., Conclusions: Higher circulating memory CD4 + T cells may reflect liver fat severity. CD8 + CD57 + cells were associated with liver fat presence and severity, but replication of findings is required., Competing Interests: BP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Niedecker, Delaney, Doyle, Sparks, Sitlani, Buzkova, Zeb, Tracy, Psaty, Budoff and Olson.)

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination., (© 2024. The Author(s).)

In this study, we aimed to evaluate the association of innate and adaptive immune cell subsets in peripheral blood mononuclear cells (PBMCs) with hip fracture. To conduct this study, we used data from the Cardiovascular Health Study (CHS), a U.S. multicenter observational cohort of community-dwelling men and women aged ≥ 65 years. Twenty-five immune cell phenotypes were measured by flow cytometry from cryopreserved PBMCs of CHS participants collected in 1998-1999. The natural killer (NK), γδ T, T helper 17 (Th17), and differentiated/senescent CD4 + CD28 - T cell subsets were pre-specified as primary subsets of interest. Hip fracture incidence was assessed prospectively by review of hospitalization records. Multivariable Cox hazard models evaluated associations of immune cell phenotypes with incident hip fracture in sex-stratified and combined analyses. Among 1928 persons, 259 hip fractures occurred over a median 9.7 years of follow-up. In women, NK cells were inversely associated with hip fracture [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.60-0.99 per one standard deviation higher value] and Th17 cells were positively associated with hip fracture [HR 1.18, 95% CI 1.01-1.39]. In men, γδ T cells were inversely associated with hip fracture [HR 0.60, 95% CI 0.37-0.98]. None of the measured immune cell phenotypes were significantly associated with hip fracture incidence in combined analyses. In this large prospective cohort of older adults, potentially important sex differences in the associations of immune cell phenotypes and hip fracture were identified. However, immune cell phenotypes had no association with hip fracture in analyses combining men and women., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: People who enter custody have complex health issues and comorbidities may include alcohol use disorders. We investigated clinical service provision and comorbidities recorded among individuals with a likely alcohol withdrawal syndrome within prison in New South Wales, Australia., Methods: For this clinical case series review, electronic medical data were used to identify 50 people entering custody between August and November 2018 who likely had a treated alcohol withdrawal syndrome. We aimed for a 3:2 ratio of men and women, and a 1:1 ratio of Aboriginal and non-Aboriginal individuals. Data were extracted using a purposefully designed tool which included current alcohol withdrawal management, comorbidities and alcohol relapse prevention approaches used or recommended., Results: Thirty-eight men and 12 women, of whom 22 were Aboriginal, were included. Twenty-nine individuals (58%) reported a history of medical comorbidities. Thirty-five (70%) reported using other substances and over half (60%) had a diagnosis of mental health disorders. Fourteen (28%) individuals had a record of receiving brief intervention and five (10%) of motivational interviewing. Twenty-three individuals (46%) were referred to and seen by drug and alcohol clinicians. Only seven (14%) of the sample had pre-release community care plans., Discussion and Conclusions: Individuals treated for an alcohol withdrawal syndrome in New South Wales prisons have a high prevalence of medical comorbidities and other substance use. Clinical interventions focused on alcohol withdrawal management, and relapse prevention interventions were not recorded for most individuals. Service innovation and expansion are needed to increase the provision of post-withdrawal management., (© 2023 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Fetal alcohol spectrum disorder (FASD) is a lifelong disability of varying severity that occurs among individuals prenatally exposed to alcohol. Among Aboriginal and Torres Strait Islander (Indigenous) Australians, the effects of colonisation and ongoing racism could increase the risk of alcohol consumption during pregnancy. Much of the research and the effort towards prevention of and caring for people with FASD in Indigenous communities has been targeted towards women and children. More support and effort towards prevention of FASD is needed across the whole Indigenous community. In this paper, we discuss several areas for increased involvement by Indigenous men in future FASD research, prevention, care and support., (© 2023 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis., (© 2023. The Author(s).)

Inflammatory protein biomarkers induced by immune responses have been associated with cognitive decline and the pathogenesis of Alzheimer's disease (AD). Here, we investigate associations between a panel of inflammatory biomarkers and cognitive function and incident dementia outcomes in the well-characterized Framingham Heart Study Offspring cohort. Participants aged ≥40 years and dementia-free at Exam 7 who had a stored plasma sample were selected for profiling using the OLINK proteomics inflammation panel. Cross-sectional associations of the biomarkers with cognitive domain scores (N = 708, 53% female, 22% apolipoprotein E (APOE) ε4 carriers, 15% APOE ε2 carriers, mean age 61) and incident all-cause and AD dementia during up to 20 years of follow-up were tested. APOE genotype-stratified analyses were performed to explore effect modification. Higher levels of 12 and 3 proteins were associated with worse executive function and language domain factor scores, respectively. Several proteins were associated with more than one cognitive domain, including IL10, LIF-R, TWEAK, CCL19, IL-17C, MCP-4, and TGF-alpha. Stratified analyses suggested differential effects between APOE ε2 and ε4 carriers: most ε4 carrier associations were with executive function and memory domains, whereas most ε2 associations were with the visuospatial domain. Higher levels of TNFB and CDCP1 were associated with higher risks of incident all-cause and AD dementia. Our study found that TWEAK concentration was associated both with cognitive function and risks for AD dementia. The association of these inflammatory biomarkers with cognitive function and incident dementia may contribute to the discovery of therapeutic interventions for the prevention and treatment of cognitive decline., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Objective: Alcohol and other drug (AoD) use is a significant factor in the poor health status of people in prison. Our aim is to explore associations of alcohol consumption with tobacco and illicit drug use among Aboriginal and non-Aboriginal people in prison to inform health services, clinical care and support., Methods: We analysed the alcohol, tobacco and illicit drug use data of the 2015 Network Patient Health Survey of adults in custody in New South Wales (n=1,132). A comparative analysis of Aboriginal to non-Aboriginal participants including bi-variant and multivariant analysis was undertaken., Results: Significantly more Aboriginal than non-Aboriginal participants reported alcohol consumption before prison that was consistent with possible dependence. More Aboriginal than non-Aboriginal participants used cannabis on a daily or almost on daily basis before prison. There was significant association between alcohol and cannabis use among Aboriginal participants., Conclusions: There are differences in Aboriginal and non-Aboriginal AoD use patterns, which should be considered when providing treatment and support programs within and post-release from prison., Implications for Public Health: Specific programs are needed to assist Aboriginal people in this population who co-use alcohol and cannabis., Competing Interests: Conflicts of interest None of the authors have a conflict of interest towards publishing this paper., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

A 6-minute walk test is a simple tool for assessing submaximal exercise capacity. We sought to determine whether a 6-minute walk distance (6MWD) predicts outcomes in patients with cirrhosis. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study that enrolled adults with portal hypertension during liver transplantation evaluation. We excluded subjects with an incident or prevalent portopulmonary hypertension. The 6-minute walk test was performed using standardized methods. Cox proportional hazards modeling and multivariable linear regression analysis were performed to determine the relationship between baseline 6MWD and outcomes. The study sample included 352 subjects. The mean 6MWD was 391±101 m. For each 50-meter decrease in 6MWD, there was a 25% increase in the risk of death (HR 1.25, 95% CI [1.11, 1.41], p < 0.001) after adjustment for age, gender, body mass index, MELD-Na, and liver transplant as a time-varying covariate. In a multistate model, each 50-meter decrease in 6MWD was associated with an increased risk of death before the liver transplant ( p < 0.001) but not after the transplant. 6MWD was similar to MELD-Na in discriminating mortality. Each 50-meter decrease in 6MWD was associated with an increase in all-cause ( p < 0.001) and transplant-free hospitalizations ( p < 0.001) in multivariable models for time-to-recurrent events. Shorter 6MWD was associated with worse Short Form-36 physical ( p < 0.001) and mental component scores ( p = 0.05). In conclusion, shorter 6MWD is associated with an increased risk of death, hospitalizations, and worse quality of life in patients evaluated for liver transplantation. The 6-minute walk distance may be a useful adjunct for risk assessment in patients undergoing liver transplant evaluation., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Understanding the composition of circulating immune cells with aging and the underlying biologic mechanisms driving aging may provide molecular targets to slow the aging process and reduce age-related disease. Utilizing cryopreserved cells from 996 Framingham Heart Study (FHS) Offspring Cohort participants aged 40 and older (mean 62 years, 48% female), we report on 116 immune cell phenotypes including monocytes, T-, B-, and NK cells and their subtypes, across age groups, sex, cytomegalovirus (CMV) exposure groups, smoking and other cardiovascular risk factors. The major cellular differences with CMV exposure were higher Granzyme B+ cells, effector cells, and effector-memory re-expressing CD45RA (TEMRA) cells for both CD4+ and CD8+. Older age was associated with lower CD3+ T cells, lower naïve cells and naïve/memory ratios for CD4+ and CD8+. We identified many immune cell differences by sex, with males showing lower naïve cells and higher effector and effector memory cells. Current smokers showed lower pro-inflammatory CD8 cells, higher CD8 regulatory type cells and altered B cell subsets. No significant associations were seen with BMI and other cardiovascular risk factors. Our cross-sectional observations of immune cell phenotypes provide a reference to further the understanding of the complexity of immune cells in blood, an easily accessible tissue.

Research into opportunities for prevention including health promotion information about alcohol and other drugs (AoD) harms for people who go to prison is sparce. This is despite there being ample research reporting how much and how frequently AoD have been used by people who go to prison. This article describes results from a qualitative thematic analysis of interviews with 31 men in a Sydney prison, about where they first received health promotion information about AoD-related harms and their first-ever treatment episode. No participant reported receiving education on AoD harms or treatment support services in primary school or high school. Only one participant received their first treatment episode through a health service (in his case from a doctor) and none reported being screened for AoD use at a health service. Almost all (n = 27) participants had their first session with a trained AoD professional through the criminal justice system. Pro-active screening in health services for AoD use disorders and referral to appropriate health services is needed., (© 2022 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Introduction: Cellular senescence is a feature of aging implicated in the pathophysiology of diabetes mellitus (DM). Whether senescent lymphocytes are associated with the future occurrence of DM is uncertain., Methods: We used cryopreserved peripheral blood mononuclear cells collected from 1860 Cardiovascular Health Study participants (average age 80.2 years) and flow cytometry immunophenotyping to evaluate the longitudinal relationships of naive (CD45RA + ), memory (CD45RO + ), senescent (CD28 - ), and T effector memory RA + (TEMRA) (CD28 - CD57 + CD45RA + ) CD4 + and CD8 + T cells, and memory B cells (CD19 + CD27 + ), with the risk of incident DM. In exploratory analyses we evaluated the relationships of 13 additional innate lymphocyte and CD4 + and CD8 + subsets with incident DM risk., Results: Over a median follow-up time of 8.9 years, 155 cases of incident DM occurred. In Cox models adjusted for demographic variables (age, sex, race, study site and flow cytometry analytical batch) or diabetes risk factors (demographic variables plus education, body mass index, smoking status, alcohol use, systolic blood pressure, hypertension medication use and physical activity), no significant associations were observed for any CD4 + , CD8 + or CD19 + cell phenotypes with incident DM., Conclusions: These results suggest the frequencies of naive, memory and senescent T cells and memory B cells are not strongly associated with incident DM risk in older adults., (© 2022 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Aboriginal and Torres Strait Islander (Aboriginal) young people seek information and access health services for their sexual health needs. This study examined Aboriginal young people's perspectives on sexual health services and sex education in Australia. Overall, 51 Aboriginal people aged 16-26 years were interviewed by peer researchers in Sydney, Australia in 2019-2020. The findings suggest that the internet was used to assess information quickly and confidentially, but Aboriginal young people questioned its reliability and accuracy. Family, Elders and peers were seen as sources of advice because they had real-life experience and highlighted intergenerational learning that occurs in Aboriginal communities. School-based sex education programmes had mixed reviews, with a preference for programmes delivered by external specialists providing anonymity, clear and accurate information about sex and relationships and positive approaches to sex education, including how to gain consent before sex. There was a need identified for school-based programmes to better consider the needs of Aboriginal young people, including those who identified as LGBTQI + . Aboriginal Medical Services were highly valued for providing culturally safe access to services, while sexual health clinics were valued for providing specialised confidential clinical services with low levels of judgement.

Aims: Circulating inflammatory markers are associated with incident heart failure (HF), but prospective data on associations of immune cell subsets with incident HF are lacking. We determined the associations of immune cell subsets with incident HF as well as HF subtypes [with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF)]., Methods and Results: Peripheral blood immune cell subsets were measured in adults from the Multi-Ethnic Study of Atherosclerosis (MESA) and Cardiovascular Health Study (CHS). Cox proportional hazard models adjusted for demographics, HF risk factors, and cytomegalovirus serostatus were used to evaluate the association of the immune cell subsets with incident HF. The average age of the MESA cohort at the time of immune cell measurements was 63.0 ± 10.4 years with 51% women, and in the CHS cohort, it was 79.6 ± 4.4 years with 62% women. In the meta-analysis of CHS and MESA, a higher proportion of CD4+ T helper (Th) 1 cells (per one standard deviation) was associated with a lower risk of incident HF [hazard ratio (HR) 0.91, (95% CI 0.83-0.99), P = 0.03]. Specifically, higher proportion of CD4+ Th1 cells was significantly associated with a lower risk of HFrEF [HR 0.73, (95% CI 0.62-0.85), <0.001] after correction for multiple testing. No association was observed with HFpEF. No other cell subsets were associated with incident HF., Conclusions: We observed that higher proportions of CD4+ Th1 cells were associated with a lower risk of incident HFrEF in two distinct population-based cohorts, with similar effect sizes in both cohorts demonstrating replicability. Although unexpected, the consistency of this finding across cohorts merits further investigation., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Lower CD4 + cell count in people with HIV infection (PWH) is associated with increased cardiovascular disease (CVD) risk. Whether subsets of CD4 + T helper cells are linked with CVD is unclear., Objectives: The aim of this study was to explore the association between peripherally circulating CD4 + T cell subsets and incident CVD., Methods: Data from 1,860 participants (1,270 PWH) without prevalent CVD from the VACS (Veterans Aging Cohort Study), a prospective, observational cohort of veterans with and without HIV infection, were analyzed. T cell subsets were quantified in baseline samples using flow cytometry. Incident CVD events were identified using International Classification of Diseases-9th Revision and International Classification of Diseases-10th Revision diagnosis and procedure codes. Participants were followed from baseline date (2005-2006) to the first of CVD incidence, death, or September 30, 2016. Cox proportional hazards regression was used to model associations between these T cell subsets and the risk for incident CVD while adjusting for demographics and other CVD risk factors., Results: The median participant age at baseline was 51.6 years. Most were male (94%) and of Black race (69.1%). There were 344 incident CVD events (219 in PWH) during follow-up (median 9.8 years). In PWH, higher proportions (per SD increment) of T helper type 17 cells (adjusted HR: 1.19; 95% CI: 1.08-1.31), T effector memory cells re-expressing CD45RA (adjusted HR: 1.19; 95% CI: 1.07-1.34), and CD28 null cells (adjusted HR: 1.18; 95% CI: 1.03-1.34) were significantly associated with an increased risk for incident CVD. Among those without HIV infection, no T cell subsets were significantly associated with CVD., Conclusions: Among PWH, T helper type 17 cells, senescent cells, and CD4 + T effector memory cells re-expressing CD45RA were significantly associated with incident CVD that was not explained by CVD risk factors., Competing Interests: Funding Support and Author Disclosures This material is based upon work supported by the VA, the Veterans Health Administration, and the Office of Research and Development, National Institute on Alcohol Abuse and Alcoholism (grants U24-AA020794, U01-AA020790, U24-AA022001, and U10 AA013566), and grant R01HL125032. Dr So-Armah’s work on this project was supported by National Institutes of Health grants K01HL134147, R61DA047032, and P30AI042853. The funders had no role in the study design or the collection, analyses, and interpretation of data. The views expressed in this paper are those of the authors and do not necessarily reflect the position or policy of the VA. Dr Beckman is a consultant for AstraZeneca, Bristol Myers Squibb, Amgen, Merck, Sanofi, Antidote Pharmaceutical, and Boehringer Ingelheim; and serves on data and safety monitoring committees for Bayer and Novartis. Dr McDonnell is an employee and shareholder of 10x Genomics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Inflammatory cytokines and chemokines related to the innate and adaptive immune system have been linked to neuroinflammation in Alzheimer's Disease, dementia, and cognitive disorders. We examined the association of 11 plasma proteins (CD14, CD163, CD5L, CD56, CD40L, CXCL16, SDF1, DPP4, SGP130, sRAGE, and MPO) related to immune and inflammatory responses with measures of cognitive function, brain MRI and dementia risk. We identified Framingham Heart Study Offspring participants who underwent neuropsychological testing (n = 2358) or brain MRI (n = 2100) within five years of the seventh examination where a blood sample for quantifying the protein biomarkers was obtained; and who were followed for 10 years for incident all-cause dementia (n = 1616). We investigated the association of inflammatory biomarkers with neuropsychological test performance and brain MRI volumes using linear mixed effect models accounting for family relationships. We further used Cox proportional hazards models to examine the association with incident dementia. False discovery rate p-values were used to account for multiple testing. Participants included in the neuropsychological test and MRI samples were on average 61 years old and 54% female. Participants from the incident dementia sample (average 68 years old at baseline) included 124 participants with incident dementia. In addition to CD14, which has an established association, we found significant associations between higher levels of CD40L and myeloperoxidase (MPO) with executive dysfunction. Higher CD5L levels were significantly associated with smaller total brain volumes (TCBV), whereas higher levels of sRAGE were associated with larger TCBV. Associations persisted after adjustment for APOE ε4 carrier status and additional cardiovascular risk factors. None of the studied inflammatory biomarkers were significantly associated with risk of incident all-cause dementia. Higher circulating levels of soluble CD40L and MPO, markers of immune cell activation, were associated with poorer performance on neuropsychological tests, while higher CD5L, a key regulator of inflammation, was associated with smaller total brain volumes. Higher circulating soluble RAGE, a decoy receptor for the proinflammatory RAGE/AGE pathway, was associated with larger total brain volume. If confirmed in other studies, this data indicates the involvement of an activated immune system in abnormal brain aging., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: Despite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes - key determinants of inflammation propagation versus resolution - and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke., Methods: We investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models., Results: We observed associations of intermediate monocytes, early-activated CD4 + T cells, and both CD4 + and CD8 + T cells producing interleukin-4 after cytokine stimulation (T h2 and T c2 , respectively) with higher risk for incident stroke; effect sizes ranged from 35% to 62% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women., Conclusions: Circulating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Aboriginal and Torres Strait Islander ('Indigenous') Australians experience a greater burden of disease from alcohol consumption than non-Indigenous peoples. Brief interventions can help people reduce their consumption, but people drinking at risky levels must first be detected. Valid screening tools (e.g., AUDIT-C) can help clinicians identify at-risk individuals, but clinicians also make unstructured assessments. We aimed to determine how frequently clinicians make unstructured risk assessments and use AUDIT-C with Indigenous Australian clients. We also aimed to determine the accuracy of unstructured drinking risk assessments relative to AUDIT-C screening. Finally, we aimed to explore whether client demographics influence unstructured drinking risk assessments., Methods: We performed cross-sectional analysis of a large clinical dataset provided by 22 Aboriginal Community Controlled Health Services in Australia. We examined instances where clients were screened with unstructured assessments and with AUDIT-C within the same two-monthly period. This aggregated data included 9884 observations. We compared the accuracy of unstructured risk assessments against AUDIT-C using multi-level sensitivity and specificity analysis. We used multi-level logistic regression to identify demographic factors that predict risk status in unstructured assessments while controlling for AUDIT-C score., Results: The primary variables were AUDIT-C score and unstructured drinking risk assessment; demographic covariates were client age and gender, and service remoteness. Clinicians made unstructured drinking risk assessments more frequently than they used AUDIT-C (17.11% and 10.85% of clinical sessions respectively). Where both measures were recorded within the same two-month period, AUDIT-C classified more clients as at risk from alcohol consumption than unstructured assessments. When using unstructured assessments, clinicians only identified approximately one third of clients drinking at risky levels based on their AUDIT-C score (sensitivity = 33.59% [95% CI 22.03, 47.52], specificity = 99.35% [95% CI 98.74, 99.67]). Controlling for AUDIT-C results and demographics (gender and service remoteness), clinicians using unstructured drinking risk assessments were more likely to classify older clients as being at risk from alcohol consumption than younger clients., Conclusions: Evidence-based screening tools like AUDIT-C can help clinicians ensure that Indigenous Australian clients (and their families and communities) who are at risk from alcohol consumption are better detected and supported., (© 2022. The Author(s).)

Rationale: Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. Objectives: We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high-attenuation areas, and FVC in four independent cohorts. Methods: We included participants with measured monocyte counts and computed tomographic (CT) imaging enrolled in MESA (Multi-Ethnic Study of Atherosclerosis, n  = 484), AGES-Reykjavik (Age/Gene Environment Susceptibility Study, n  = 3,547), COPDGene (Genetic Epidemiology of COPD, n  = 2,719), and the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, n  = 646). Measurements and Main Results: After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.0-1.8), AGES-Reykjavik (OR, 1.2; 95% CI, 1.1-1.3), COPDGene (OR, 1.3; 95% CI, 1.2-1.4), and ECLIPSE (OR, 1.2; 95% CI, 1.0-1.4). A higher monocyte count was associated with ILA progression over 5 years in AGES-Reykjavik (OR, 1.2; 95% CI, 1.0-1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater high-attenuation areas in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. Conclusions: Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.

Objective: A higher proportion of circulating memory CD4+ T cells is associated with prevalent diabetes mellitus in persons with HIV (PWH) and HIV-negative persons. We assessed whether circulating T-cell subsets could also identify individuals who will subsequently develop diabetes., Design: This is a longitudinal follow-up study of PWH and similar HIV-negative individuals from the Veterans Aging Cohort Study who provided peripheral mononuclear blood cells between 2005 and 2007., Methods: We quantified T-cell subsets using flow cytometry and functional assays to identify CD4+ and CD8+ naive, activated, senescent, memory (central, effector, and effector RA+), and TH1, TH2, and TH17-phenotype cells. The occurrence of an incident diabetes diagnosis (i.e. after baseline blood draw) was adjudicated by a two-physician chart review. Cox proportional hazards models adjusted for traditional risk factors, cytomegalovirus serostatus, and plasma inflammatory biomarkers assessed the relationship between T-cell subsets and incident diabetes., Results: One thousand, eight hundred and thirty-seven participants (1259 PWH) without diabetes at baseline were included; 69% were black, 95% were men, and median follow-up was 8.6 years. Higher baseline frequencies of CD4+ T effector memory RA+ (TEMRA) cells defined as CD45RA+ CD27- (P = 0.04) and senescent T cells defined as CD4+ CD28- (P = 0.04) were associated with incident diabetes in PWH only., Conclusions: Higher frequencies of CD4+ TEMRA and CD4+ CD28- T cells were associated with incident diabetes in PWH only after adjustment for other factors. Additional studies are necessary to assess whether these cells act in blood via inflammatory mediators or reflect T-cell populations in metabolically active tissues., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The worldwide pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected an estimated 200 million people with over 4 million deaths. Although COVID-19, the disease caused by the SARS-CoV-2 virus, is primarily a respiratory disease, an increasing number of neurologic symptoms have been reported. Some of these symptoms, such as loss of smell or taste, are mild and non-life threatening, while others, such as stroke or seizure, are more critical. Many of these symptoms remain long after the acute illness has passed, a phenomenon known as "long COVID" or postacute sequelae of SARS-CoV-2 infection (PASC). Neurological symptoms can be difficult to study due to the complexity of the central and peripheral nervous system. These neurologic symptoms can be difficult to identify and quantitate. This narrative review will describe approaches for assessing neurologic manifestations of COVID-19, with examples of the data they provide, as well as some directions for future research to aid in understanding the pathophysiology of COVID-19-related neurological implications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aims: Opioid agonist treatment is effective but resource intensive to administer safely in custodial settings, leading to significant under-treatment of opioid dependence in these settings world-wide. This study assessed the safety of subcutaneous slow-release depot buprenorphine in custody., Design: Open-label, non-randomized trial., Setting: Correctional centres in New South Wales, Australia., Participants: Sixty-seven men and women, aged ≥ 18 years of various security classifications with a diagnosis of moderate to severe DSM-5 opioid use disorder currently serving a custodial sentence of ≥ 6 months were recruited between November 2018 and July 2019. Patients not in opioid agonist treatment at recruitment commenced depot buprenorphine; patients already stable on oral methadone treatment were recruited to the comparison arm., Intervention and Comparator: Depot buprenorphine (CAM2038 weekly for 4 weeks then monthly) and daily oral methadone., Measurements: Safety was assessed by adverse event (AE) monitoring and physical examinations at every visit. Participants were administered a survey assessing self-reported diversion and substance use at baseline and weeks 4 and 16., Findings: Retention in depot buprenorphine treatment was 92.3%. Ninety-four per cent of patients reported at least one adverse event, typically mild and transient. No diversion was identified. The prevalence of self-reported non-prescribed opioid use among depot buprenorphine patients decreased significantly between baseline (97%) and week 16 (12%, odds ratio = 0.0035, 95% confidence interval = 0.0007-0.018, P < 0.0001)., Conclusions: This first study of depot buprenorphine in custodial settings showed treatment retention and outcomes comparable to those observed in community settings and for other opioid agonist treatment used in custodial settings, without increased risk of diversion., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Purpose: The purpose of this study is to describe what a sample of men in prison believe works well for the delivery of prison-based group alcohol and other drug (AoD) treatment programs. The authors hope the findings will help inform future practise in AoD program delivery in prison., Design/methodology/approach: A qualitative research paper reporting on a thematic analysis of in-depth interviews with 30 male prisoners on their perspectives on AoD group treatment approaches., Findings: Results indicate that matching readiness and motivation to start treatment is important for group success. Program content must be relevant and delivered by empathic facilitators who maintain confidentiality. It would be advantageous if one of the program facilitators was a peer with personal experience of overcoming an AoD use disorder., Originality/value: According to the authors' knowledge, this is one of few qualitative studies into the delivery of AoD treatment for men in prison and the only study of its kind in Australia. The consumer perspective is an important element in improving quality of treatment provision., (© Emerald Publishing Limited.)

Background: Peripheral inflammation is associated with increased risk for dementia. Neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), and mean platelet volume (MPV), are easily measured circulating blood cell phenotypes reflecting chronic peripheral inflammation, but their association with dementia status is unclear., Objective: We sought to investigate the cross-sectional association of these inflammatory measures with neuropsychological (NP) test performance, and brain magnetic resonance imaging (MRI) measures in the Framingham Heart Study (FHS) Offspring, Third-generation, and Omni cohorts., Methods: We identified FHS participants who attended an exam that included a complete blood cell count (CBC) and underwent NP testing (n = 3,396) or brain MRI (n = 2,770) within five years of blood draw. We investigated the association between NLR, RDW, and MPV and NP test performance and structural MRI-derived volumetric measurements using linear mixed effect models accounting for family relationships and adjusting for potential confounders., Results: Participants were on average 60 years old, 53% female, and about 80% attended some college. Higher NLR was significantly associated with poorer performance on visual memory, and visuospatial abilities, as well as with larger white matter hyperintensity volume. We also observed associations for higher RDW with poorer executive function and smaller total cerebral brain volume., Conclusion: Chronic peripheral inflammation as measured by NLR and RDW was associated with worse cognitive function, reduced brain volume, and greater microvascular disease in FHS participants. If confirmed in other samples, CBC may provide informative and cost-effective biomarkers of abnormal brain aging in the community.

Introduction and Aims: Crystal methamphetamine (CM) is associated with a range of physical and mental health harms and may be of particular concern among young people at risk of early, problematic substance use, such as those in contact with the criminal justice system. This study aimed to investigate the prevalence and correlates of regular (i.e. at least weekly) CM use among young people preceding entry into custody., Design and Methods: Data were collected from 207 participants aged 14-18 years as part of the 2015 Young People in Custody Health Survey, a cross-sectional survey of youth in custody in New South Wales, Australia. Participants were administered face-to-face structured interviews assessing sociodemographic, childhood and family characteristics, offending history, substance use and psychopathology. Multivariable logistic regression analyses were conducted to identify factors independently associated with regular CM use., Results: Regular CM use was reported by 31% of participants and was independently associated with higher levels of antisocial traits/behaviour [adjusted odds ratio (AOR) 1.13, 95% confidence interval (CI) 1.02, 1.25], increased polydrug use (AOR 1.34, 95% CI 1.14, 1.58), injecting drug use (AOR 4.06, 95% CI 1.02, 16.16) and meeting symptom thresholds for two or more current psychological disorders (AOR 3.20, 95% CI 1.15, 8.94)., Discussion and Conclusions: Regular CM users present with more complex comorbidity than other young people in custody, increasing the health-care burden in custodial and community settings. Early identification and appropriate treatment of this comorbidity is crucial to improving the health, psychosocial and behavioural outcomes of this vulnerable group., (© 2020 Australasian Professional Society on Alcohol and other Drugs.)

BackgroundImmunomodulatory therapy may help prevent heart failure (HF). Data on immune cells and myocardial remodeling in older adults with cardiovascular risk factors are limited.MethodsIn the Multi-Ethnic Study of Atherosclerosis cohort, 869 adults had 19 peripheral immune cell subsets measured and underwent cardiac MRI during the baseline exam, of which 321 had assessment of left ventricular global circumferential strain (LV-GCS). We used linear regression with adjustment for demographics, cardiovascular risk factors, and cytomegalovirus serostatus to evaluate the cross-sectional association of immune cell subsets with left ventricular mass index (LVMI) and LV-GCS.ResultsThe average age of the cohort was 61.6 ± 10.0 years and 53% were women. Higher proportions of γ/δ T cells were associated with lower absolute (worse) LV-GCS (-0.105% [95% CI -0.164%, -0.046%] per 1 SD higher proportion of γ/δ T cells, P = 0.0006). This association remained significant after Bonferroni's correction. Higher proportions of classical monocytes were associated with worse absolute LV-GCS (-0.04% [95% CI -0.07%, 0.00%] per 1 SD higher proportion of classical monocytes, P = 0.04). This did not meet significance after Bonferroni's correction. There were no other significant associations with LV-GCS or LVMI.ConclusionPathways associated with γ/δ T cells may be potential targets for immunomodulatory therapy targeted at HF prevention in populations at risk.FundingContracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 and grant R01 HL98077 from the National Heart, Lung, and Blood Institute/NIH and grants KL2TR001424, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences/NIH.

[Figure: see text].

Background: Unhealthy alcohol use is a key concern for Aboriginal and Torres Strait Islander ('Indigenous Australian') communities. Due to systematic disadvantage and inter-generational trauma, Indigenous Australians may be less likely to have satisfied basic psychological needs (autonomy, competence, and relatedness). When people are need-thwarted, they may engage in compensatory behaviours to feel better in the short-term. We explore the relationship between perceived basic psychological needs satisfaction and alcohol consumption use among Indigenous Australians. Better understanding the functions that alcohol may play for some Indigenous Australian drinkers may aid communities, clinicians, and policy makers in improving programs for reducing drinking-related harms., Methods: We performed a cross-sectional survey of Indigenous Australians (aged 16 years or older) living in two South Australian communities. Participants were eligible if they had consumed any alcohol in the past 12 months. Spearman correlations and linear regressions were used to determine if feeling more autonomous, competent, and related to others (need satisfied) while drinking, was linked to alcohol consumption and dependence., Results: Controlling for participant demographics, reporting feeling need satisfied while drinking was linked to drinking more alcohol per day, reporting more frequent symptoms of alcohol dependence, spending more money on alcohol, and scoring higher on the AUDIT-C., Conclusions: Unhealthy drinking may partly stem from attempts to satisfy basic psychological needs. Programs which support Indigenous Australians to meet basic psychological needs could reduce attempts to meet psychological needs through alcohol consumption.

Background and Aims: Portopulmonary hypertension (POPH) was previously associated with a single-nucleotide polymorphism (SNP) rs7175922 in aromatase (cytochrome P450 family 19 subfamily A member 1 [CYP19A1]). We sought to determine whether genetic variants and metabolites in the estrogen signaling pathway are associated with POPH., Approach and Results: We performed a multicenter case-control study. POPH patients had mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dyn-sec/cm -5 , and pulmonary artery wedge pressure ≤15 mm Hg without another cause of pulmonary hypertension. Controls had advanced liver disease, right ventricular (RV) systolic pressure <40 mm Hg, and normal RV function by echocardiography. We genotyped three SNPs in CYP19A1 and CYP1B1 using TaqMan and imputed SNPs in estrogen receptor 1 using genome-wide markers. Estrogen metabolites were measured in blood and urine samples. There were 37 patients with POPH and 290 controls. Mean age was 57 years, and 36% were female. The risk allele A in rs7175922 (CYP19A1) was significantly associated with higher levels of estradiol (P = 0.02) and an increased risk of POPH (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.12-4.91; P = 0.02) whereas other SNPs were not. Lower urinary 2-hydroxyestrogen/16-α-hydroxyestrone (OR per 1-ln decrease = 2.04; 95% CI, 1.16-3.57; P = 0.01), lower plasma levels of dehydroepiandrosterone-sulfate (OR per 1-ln decrease = 2.38; 95% CI, 1.56-3.85; P < 0.001), and higher plasma levels of 16-α-hydroxyestradiol (OR per 1-ln increase = 2.16; 95% CI, 1.61-2.98; P < 0.001) were associated with POPH., Conclusions: Genetic variation in aromatase and changes in estrogen metabolites were associated with POPH., (© 2020 by the American Association for the Study of Liver Diseases.)

Background: Hypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP)., Methods: We assayed immune cells from cryopreserved samples collected at the baseline examination (2000-2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10 years. The analysis provides estimates of the association with blood pressure level., Results: The mean age of the MESA participants at baseline was 64 ± 10 years and 53% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40 mmHg [95% confidence interval (CI) 1.34-3.42] higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88 mmHg (95% CI 0.82-2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14 ++ CD16 - ) was associated with 2.01 mmHG (95% CI 0.79-3.24) lower average systolic blood pressure. There were no associations of CD4 + T helper cell subsets with average systolic blood pressure., Conclusion: These findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.

Introduction: Aboriginal and Torres Strait Islander people are vastly over-represented in Australian prisons. Many people in prison attribute in some way their offences to alcohol and/or other drug (AOD) use. This paper aims to understand AOD use before first and between terms in prison, among a group of Aboriginal men enrolled in a prison-based AOD treatment program. It examines opportunities for prevention or treatment that might interrupt the cycle of alcohol consumption, offending and imprisonment., Methods: A thematic analysis of in-depth interviews with 14 Aboriginal men in an urban prison., Results: Participants had low levels of formal education, none having completed high school and had spent limited or no time in the workforce. All 14 spoke of being negatively affected by AOD use within their families. First alcohol and cannabis use were around age 12-14 years, first amphetamines and/or heroin use was around age 15. As adults, they had unstable accommodation and when released from prison returned to the same situation they had been in previously. Most believed they would not have offended and subsequently imprisoned if they did not have a substance use disorder., Discussion and Conclusion: Without further support post-prison, the men in this study are likely to return to the same situation and continue their AOD use. Further efforts are needed to support families with substance use disorders and to give young Aboriginal and Torres Strait Islander people better education and training opportunities., (© 2020 Australasian Professional Society on Alcohol and other Drugs.)