Health and socio-economic inequalities by sexual orientation among older women in the United Kingdom: findings from the UK Household Longitudinal Study

Lesbian, gay, bisexual and queer (LGBQ) women living in the United Kingdom (UK) experience worse health than their heterosexual peers throughout their lives, but less is known about health inequalities in older age. This study uses population-level data to examine inequalities among LGBQ older women and women who prefer not to disclose their sexuality, compared to heterosexual women. Analyses use data from women aged 50 and older who were active in Waves 3 and 7 of the UK Household Longitudinal Study (also known as Understanding Society) (N = 8,209) to examine inequalities in socio-economic conditions, health and alcohol consumption across sexual orientation groups. LGBQ older women are on average younger and have higher socio-economic resources than their heterosexual peers. In contrast, women who prefer not to disclose their sexual orientation are older and have the lowest income and educational qualifications. Results of the health inequalities analyses show that LGBQ older women are almost twice as likely as heterosexual older women to engage in harmful alcohol consumption. Older women who prefer not to disclose their sexuality have worse physical and mental health than heterosexual older women. The health of LGBQ older women and women who prefer not to disclose their sexual orientation is one of the most neglected research areas in UK gerontology. Findings of this study contribute to our understanding of their social and health circumstances, and illuminate methodological limitations in existing data

Race/ethnic inequalities in early adolescent development in the United Kingdom and United States

BACKGROUND Comparative literature investigating race/ethnic patterning of children’s health has found racial/ethnic minority status to be linked to health disadvantages. Less is known about differences during early adolescence, a period during which health outcomes are linked to later life health. OBJECTIVE Using the UK Millennium Cohort Study (n = 10,188) and the US Early Childhood Longitudinal Survey–Kindergarten Cohort (n ~ 6,950), we examine differences in socioemotional and cognitive development among 11-year-old adolescents and the contribution of family resources in explaining any observed differences, including socioeconomic, cultural traditions, and psychosocial resources. RESULTS Adverse socioemotional health and cognitive development were associated with race/ethnic minority status in both countries. In the United States, we found that cultural resources and family socioeconomic capital played a large role in attenuating differences in problem behaviors between Asian American, Black, and Latino adolescents and their White peers. In the United Kingdom, the explanatory factors explaining differences in problem behaviors varied by racial/ethnic group. In both contexts, family resources cannot explain the sizable cross-country differences in verbal skills. In the United Kingdom, Indian adolescents had nearly one-third of a standard deviation increase in their verbal scores whereas in the United States, Black and Latino adolescents had scores nearly two-fifths and one-fifth of a standard deviation below the mean, respectively. CONTRIBUTION We use a detailed race/ethnic classification in the investigation of racial/ethnic inequalities across the United States and United Kingdom. There are strong family resource effects, suggesting that relative family advantages and disadvantages do have meaningful associations with adolescent socioemotional and cognitive development. Although levels of resources do explain some cross-national differences, there appears to be a broader range of family background variables in the United Kingdom that influence adolescent development. Our findings point to the critical role of both the extent and nature of family social capital in affecting adolescent development

Post-translational modifications of lipid-activated nuclear receptors: Focus on metabolism

Post-translational modifications (PTM) occur to nearly all proteins, are catalysed by specific enzymes and are subjected to tight regulation. They have been shown to be a powerful means by which the function of proteins can be modified resulting in diverse effects. Technological advances such as the increased sensitivity of mass spectrometry-based techniques and availability of mutant animal models have enhanced our understanding of the complexities of their regulation and the effect they have on protein function. However, the role that PTMs have in a pathological context still remains unknown for the most part. PTMs enable the modulation of nuclear receptor function in a rapid and reversible manner in response to varied stimuli, thereby dramatically altering their activity in some cases. This review will focus on acetylation, phosphorylation, sumoylation and O-GlcNAcylation, which are the four most studied PTMs affecting lipid-regulated nuclear receptor biology, and the implications of such modifications on metabolic pathways under homeostatic and pathological situations. Moreover, we review recent studies on the modulation of PTMs as therapeutic targets for metabolic diseases

Intergenerational differences in beliefs about healthy eating among carers of left-behind children in rural China: a qualitative study

China's internal migration has left 61 million rural children living apart from parents and usually being cared for by grandparents. This study aims to explore caregivers' beliefs about healthy eating for left-behind children (LBC) in rural China. Twenty-six children aged 6–12 (21 LBC and 5 non-LBC) and 32 caregivers (21 grandparents, 9 mothers, and 2 uncles/aunts) were recruited in one township in rural China. Children were encouraged to keep food diaries followed by in-depth interviews with caregivers. Distinct intergenerational differences in beliefs about healthy eating emerged: the grandparent generation was concerned about not having enough food and tended to emphasise the importance of starchy foods for children's growth, due to their past experiences during the Great Famine. On the other hand, the parent generation was concerned about food safety and paid more attention to protein-source foods including meat, eggs and milk. Parents appeared to offer children high-energy food, which was viewed as a sign of economic status, rather than as part of a balanced diet. Lack of remittances from migrant parents may compromise LBC's food choices. These findings suggest the potential for LBC left in the care of grandparents, especially with experience of the Great Famine, may be at greater risk of malnutrition than children cared for by parents. By gaining an in-depth understanding of intergenerational differences in healthy eating beliefs for children, our findings could inform for the development of nutrition-related policies and interventions for LBC in rural China

Effects of LXRα phosphorylation on the regulation of lipid metabolism and hepatic fibrosis

Liver X Receptors (LXRα and β) are members of the nuclear receptor superfamily of ligand-activated transcription factors. LXRs are activated by oxidised metabolites of cholesterol and several synthetic ligands, play a crucial role in the regulation of cholesterol and fatty acid homeostasis, and act as strong modulators of inflammation and immunity. This has positioned them as targets for the treatment of several pathologies, including atherosclerosis and obesity. Besides ligand binding, LXR activity can be modulated by post-translational modifications, and previous work has shown that phosphorylation of LXRα alters its transcriptional activity in a gene-specific manner in a macrophage cell line. This thesis has focused on better understanding the regulation of LXRα phosphorylation and investigating how changes in the receptor’s phosphorylation status modulate its activity in vivo; more specifically, in relation to its effects on hepatic lipid metabolism, and the development of inflammation and fibrosis. To do so, I have used a novel mouse model that expresses a whole-body non-phosphorylatable mutant version of LXRα (S196A) and have assessed its responses to a High Fat and High Cholesterol diet, as a dietary model of Non-Alcoholic Fatty Liver Disease (NAFLD). Furthermore, I have studied how the transcriptional capacity of the mutant receptor is modulated, assessing its differential binding to DNA and to other proteins. In order to evaluate the relevance of my findings in the context of human disease, I have also examined LXR activity on the activation of human hepatic stellate cells, key players in the development of liver fibrosis. Lastly, I have sought to examine new stimulants capable of inducing LXRα phosphorylation in vitro, and how this phenomenon can be pharmacologically impaired by using already-available kinase inhibitors. Overall, the work described in this thesis shows that LXRα phosphorylation critically acts as a novel nutritional sensor that promotes a unique diet-induced transcriptome and modulates metabolic, inflammatory and fibrotic responses that are key in NAFLD progression This novel work significantly contributes to our understanding of LXRα activity in liver disease in a pre-clinical setup, and places the modulation of LXRα phosphorylation as a potential anti-inflammatory/anti-fibrotic therapeutic target

Inequalities in mental health, self-rated health, and social support among sexual minority young adults during the COVID-19 pandemic: analyses from the UK Millennium Cohort Study

Purpose Young adults who self-identify as a sexual minority may have been particularly harmed by the consequences of lockdown, closure of educational institutions, and social distancing measures as they are likely to have been confined in households that may not be supportive of their sexual orientation. We examine inequalities in the mental health and self-rated health of sexual minority young adults, compared to their heterosexual peers, at the height of lockdown restrictions in the UK. Methods We analysed data from singletons who participated in waves 6, 7, and the wave 1 COVID-19 survey (n = 2211) of the Millennium Cohort Study, a nationally representative longitudinal study of infants born in the UK between September 2000 and January 2002. Regression models compared the mental health, self-rated health, and social support of sexual minority young adults to that of their heterosexual peers. Results One in four young adults self-identified with a sexual orientation or attraction other than completely heterosexual. Sexual minority young adults had significantly lower levels of social support (β =  − 0.38, SE 0.08), poorer self-rated health (OR 3.91, 95% CI 2.41–6.34), and higher levels of psychological distress (β = 2.26, SE 0.34), anxiety (β = 0.40, SE 0.15), and loneliness (β = 0.66, SE 0.18) when compared to heterosexual young adults. Conclusions Sexual minority young adults in the UK have been detrimentally impacted by the coronavirus pandemic, experiencing inequalities in mental health, self-rated health, and social support when compared to heterosexual young adults. Implications for policy and practice include a stronger provision of safe spaces in the community and in institutions, and policies that address marginalisation and harassment

Targeted Albumin Infusions Do Not Improve Systemic Inflammation or Cardiovascular Function in Decompensated Cirrhosis

INTRODUCTION: Albumin is recommended in decompensated cirrhosis, and studies have shown potential immunomodulatory effects. However, 2 large trials of repeated albumin infusions demonstrated contrasting results between outpatients and hospitalized patients. We investigated markers of systemic inflammation, immune function, albumin binding, and cardiovascular function using samples from Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) taken at baseline, day 5, and day 10 of the trial to identify why targeted albumin infusions had no effect in hospitalized patients. METHODS: Plasma samples were analyzed from 143 patients (n = 71 targeted albumin; n = 72 standard care at baseline) for cytokines, cardiovascular markers, prostaglandin E2, the effect of plasma on macrophage function, and albumin radioligand binding and oxidation status. The sample size was based on our feasibility study, and samples were selected by a trial statistician stratified by the serum albumin level and the presence of infection at randomization and analyses performed blinded to the study arm. Data were linked to 3-month mortality and treatment groups compared. RESULTS: Increased baseline model for end-stage liver disease score, white cell count, calprotectin, CD163, tumor necrosis factor, renin, atrial natriuretic peptide, and syndecan-1 were associated with 3-month mortality. Despite infusing substantially differing volumes of albumin, there were no significant differences in inflammatory markers, albumin-prostaglandin E2 binding, or cardiovascular markers between treatment arms. DISCUSSION: Contrary to many preclinical studies, targeted intravenous albumin therapy in hospitalized decompensated cirrhosis had no effect across a broad range of systemic inflammation, albumin function, and cardiovascular mediators and biomarkers compared with standard care, consistent with the null clinical findings

Understanding the effect of ethnic density on mental health: multi-level investigation of survey data from England

Objectives To determine if living in areas where higher proportions of people of the same ethnicity reside is protective for common mental disorders, and associated with a reduced exposure to discrimination and improved social support. Finally, to determine if any protective ethnic density effects are mediated by reduced exposure to racism and improved social support