Imaging interactions between the immune and cardiovascular systems in vivo by multiphoton microscopy

Several recent studies in immunology have used multiphoton laser-scanning microscopy to visualise the induction of an immune response in real time in vivo. These experiments are illuminating the cellular and molecular interactions involved in the induction, maintenance and regulation of immune responses. Similar approaches are being applied in cardiovascular research where there is an increasing body of evidence to support a significant role for the adaptive immune system in vascular disease. As such, we have begun to dissect the role of T lymphocytes in atherosclerosis in real time in vivo. Here, we provide step-by-step guides to the various stages involved in visualising the migration of T cells within a lymph node and their infiltration into inflamed tissues such as atherosclerotic arteries. These methods provide an insight into the mechanisms involved in the activation and function of immune cells in vivo

The mental health of ex-prisoners: analysis of the 2014 English National Survey of Psychiatric Morbidity

Purpose Prisoners experience extremely high rates of psychiatric disturbance. However, ex-prisoners have never previously been identified in representative population surveys to establish how far this excess persists after release. Our purpose was to provide the first community-based estimate of ex-prisoners’ mental health in England using the data from the 2014 Adult Psychiatric Morbidity Survey (APMS). Methods APMS 2014 provides cross-sectional data from a random sample (N = 7546) of England’s household population aged 16 or above. Standardised instruments categorised psychiatric disorders and social circumstances. Participants who had been in prison were compared with the rest of the sample. Results One participant in seventy had been in prison (1.4%; 95% CI 1.1–1.7; n = 103). Ex-prisoners suffered an excess of current psychiatric problems, including common mental disorders (CMDs), psychosis, post-traumatic disorder, substance dependence, and suicide attempts. They were more likely to screen positive for attention-deficit/hyperactivity disorder and autistic traits, to have low verbal IQ, and to lack qualifications. They disclosed higher rates of childhood adversity, including physical and sexual abuse and local authority care. The odds (1.88; 95% CI 1.02–3.47) of CMDs were nearly doubled in ex-prisoners, even after adjusting for trauma and current socioeconomic adversity. Conclusions Prison experience is a marker of enduring psychiatric vulnerability, identifying an important target population for intervention and support. Moreover, the psychiatric attributes of ex-prisoners provide the context for recidivism. Without effective liaison between the criminal justice system and mental health services, the vulnerability of ex-prisoners to relapse and to reoffending will continue, with consequent personal and societal costs

Experiences of Interventions Aiming to Improve the Mental Health and Wellbeing of Children and Young People with a Long-Term Physical Condition: A Systematic Review and Meta-ethnography

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordBackground Children and young people with long term physical health conditions are at increased risk of experiencing mental health and wellbeing difficulties. However, there is a lack of research that explores the experiences of, and attitudes towards interventions aiming to improve their mental health and wellbeing. This systematic review seeks to address this gap in the literature by exploring what children and young people with long term conditions, their caregivers and health practitioners perceive to be important aspects of interventions aiming to improve their mental health and wellbeing. Methods An information specialist searched five academic databases using pre‐defined criteria for qualitative evaluations of interventions aiming to improve the mental health or wellbeing of children with long term physical conditions. Reviewers also performed supplementary citation and grey literature searches. Two reviewers independently screened titles, abstracts and full texts which met the inclusion criteria and conducted data extraction and quality assessment. Meta‐ethnography was used to synthesise the findings. Results Screening identified 60 relevant articles. We identified five overarching constructs through the synthesis: i) Getting In and Staying In, ii) Therapeutic Foundation, iii) Social Support, iv) A Hopeful Alternative and v) Empowerment. The line of argument which links these constructs together indicates that when interventions can provide an environment that allows young people to share their experiences and build empathetic relationships; it can enable participants to access social support and increase feelings of hope and empowerment. Conclusion These findings may provide a framework to inform the development of mental health interventions for this population, and evaluate existing interventions which already include some of the components or processes identified by this research. Further research is needed to establish which of the constructs identified by the line of argument are most effective in improving the mental wellbeing of young people living with long term conditions.National Institute for Health Research (NIHR

The aorta can act as a site of naïve CD4+ T-cell priming

Aims: Aortic adaptive immunity plays a role in atherosclerosis; however, the precise mechanisms leading to T-cell activation in the arterial wall remain poorly understood. Methods and results: Here, we have identified naïve T cells in the aorta of wild-Type and T-cell receptor transgenic mice and we demonstrate that naïve T cells can be primed directly in the vessel wall with both kinetics and frequency of T-cell activation found to be similar to splenic and lymphoid T cells. Aortic homing of naïve T cells is regulated at least in part by the P-selectin glycosylated ligand-1 receptor. In experimental atherosclerosis the aorta supports CD4+ T-cell activation selectively driving Th1 polarization. By contrast, secondary lymphoid organs display Treg expansion. Conclusion: Our results demonstrate that the aorta can support T-cell priming and that naïve T cells traffic between the circulation and vessel wall. These data underpin the paradigm that local priming of T cells specific for plaque antigens contributes to atherosclerosis progression

Association of body mass index in midlife with morbidity burden in older adulthood and longevity

Importance: Abundant evidence links obesity with adverse health consequences. However, controversies persist regarding whether overweight status compared with normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with longer survival and whether this occurs at the expense of greater long-term morbidity and health care expenditures. Objective: To examine the association of BMI in midlife with morbidity burden, longevity, and health care expenditures in adults 65 years and older. Design, Setting, and Participants: Prospective cohort study at the Chicago Heart Association Detection Project in Industry, with baseline in-person examination between November 1967 and January 1973 linked with Medicare follow-up between January 1985 and December 2015. Participants included 29 621 adults who were at least age 65 years in follow-up and enrolled in Medicare. Data were analyzed from January 2020 to December 2021. Exposures: Standard BMI categories. Main Outcomes and Measures: (1) Morbidity burden at 65 years and older assessed with the Gagne combined comorbidity score (ranging from -2 to 26, with higher score associated with higher mortality), which is a well-validated index based on International Classification of Diseases, Ninth Revision codes for use in administrative data sets; (2) longevity (age at death); and (3) health care costs based on Medicare linkage in older adulthood (aged ≥65 years). Results: Among 29 621 participants, mean (SD) age was 40 (12) years, 57.1% were men, and 9.1% were Black; 46.0% had normal BMI, 39.6% were overweight, and 11.9% had classes I and II obesity at baseline. Higher cumulative morbidity burden in older adulthood was observed among those who were overweight (7.22 morbidity-years) and those with classes I and II obesity (9.80) compared with those with a normal BMI (6.10) in midlife (P \u3c .001). Mean age at death was similar between those who were overweight (82.1 years [95% CI, 81.9-82.2 years]) and those who had normal BMI (82.3 years [95% CI, 82.1-82.5 years]) but shorter in those who with classes I and II obesity (80.8 years [95% CI, 80.5-81.1 years]). The proportion (SE) of life-years lived in older adulthood with Gagne score of at least 1 was 0.38% (0.00%) in those with a normal BMI, 0.41% (0.00%) in those with overweight, and 0.43% (0.01%) in those with classes I and II obesity. Cumulative median per-person health care costs in older adulthood were significantly higher among overweight participants ($12 390 [95$10 427 to $14 354]) and those with classes I and II obesity ($23 396 [95% CI, $18 474 to$28 319]) participants compared with those with a normal BMI (P \u3c .001). Conclusions and Relevance: In this cohort study, overweight in midlife, compared with normal BMI, was associated with higher cumulative burden of morbidity and greater proportion of life lived with morbidity in the context of similar longevity. These findings translated to higher total health care expenditures in older adulthood for those who were overweight in midlife

Subgroup Economic Analysis for Glioblastoma in a Health Resource-Limited Setting

BACKGROUND: The aim of this research was to evaluate the economic outcomes of radiotherapy (RT), temozolomide (TMZ) and nitrosourea (NT) strategies for glioblastoma patients with different prognostic factors. METHODOLOGY/PRINCIPAL FINDINGS: A Markov model was developed to track monthly patient transitions. Transition probabilities and utilities were derived primarily from published reports. Costs were estimated from the perspective of the Chinese healthcare system. The survival data with different prognostic factors were simulated using Weibull survival models. Costs over a 5-year period and quality-adjusted life years (QALYs) were estimated. Probabilistic sensitivity and one-way analyses were performed. The baseline analysis in the overall cohort showed that the TMZ strategy increased the cost and QALY relative to the RT strategy by $25,328.4 and 0.29, respectively; and the TMZ strategy increased the cost and QALY relative to the NT strategy by$23,906.5 and 0.25, respectively. Therefore, the incremental cost effectiveness ratio (ICER) per additional QALY of the TMZ strategy, relative to the RT strategy and the NT strategy, amounts to $87,940.6 and$94,968.3, respectively. Subgroups with more favorable prognostic factors achieved more health benefits with improved ICERs. Probabilistic sensitivity analyses confirmed that the TMZ strategy was not cost-effective. In general, the results were most sensitive to the cost of TMZ, which indicates that better outcomes could be achieved by decreasing the cost of TMZ. CONCLUSIONS/SIGNIFICANCE: In health resource-limited settings, TMZ is not a cost-effective option for glioblastoma patients. Selecting patients with more favorable prognostic factors increases the likelihood of cost-effectiveness

NHS health checks: a cross- sectional observational study on equity of uptake and outcomes

Background The National Health Checks programme aims to reduce the incidence of cardiovascular diseases and health inequalities in England. We assessed equity of uptake and outcomes from NHS Health Checks in general practices in Bristol, UK. Methods A cross-sectional study using patient-level data, from 38 general practices. We descriptively analysed the socioeconomic status (SES) of patients invited and the SES and ethnicity of those attending. Logistic regression was used to test associations between invitation and attendance, with population characteristics. Results Between June 2010 to October 2014, 31,881 patients were invited, and 13,733 NHS Health Checks completed. 47% of patients invited from the three least and 39% from the two most-deprived index of multiple deprivation quintiles, completed a Check. Proportions of invited patients, by ethnicity were 64% non-black and Asian and 31% black and Asian. Men were less likely to attend than women (OR 0.73, 95% confidence interval 0.67 to 0.80), as were patients ≤ 49 compared to ≥ 70 years (OR 0.40, 95% confidence interval 0.65 to 0.83). After controlling for SES and population characteristics, compared to patients with low CVD risk, high risk patients were more likely to be prescribed cardiovascular drugs (OR 6.2, 95% confidence interval 4.51 to 8.40). Compared to men, women (OR 01.18, 95% confidence interval 1.03 to 1.35) were more likely to be prescribed cardiovascular drugs, as were those ≤ 49 years (50–59 years, OR 1.42, 95% confidence intervals 1.13–1.79, 60–69 years, OR 1.60, 95% confidence intervals, 1.22–2.10, ≥ 70 years, OR 1.64, 95% confidence intervals, 1.14 to 2.35). Controlling for population characteristics, the following groups were most likely to be referred to lifestyle services: younger women (OR 2.22, 95% CI 1.69 to 2.94), those in the most deprived IMD quintile (OR 3.22, 95% CI 1.63 to 6.36) and those at highest risk of CVD (OR, 2.77, 95% CI 1.91 to 4.02). Conclusions We found no statistically significant evidence of inequity in attendance for an NHS Health Check by SES. Being older or a woman were associated with better attendance. Targeting men, younger patients and ethnic minority groups may improve equity in uptake for NHS Health Checks

A comparison of sexual behaviour and attitudes of healthy adolescents in a Danish high school in 1982, 1996, and 2001

AIM: To assess changes in sexual behaviour among students at a high school in Denmark from 1982 to 2001. METHODS: An anonymous self-administered questionnaire was used to compare data from three identical cross-sectional surveys performed in 1982, 1996, and 2001. RESULTS: Girls: More girls reported their first sexual intercourse before their 16th birthday in 2001 (42%) than in 1996 (29%) In 1982 it was also 42% (Chi-square for trend: p = 0.003). Fewer girls with no regular partner used condoms for their personal protection in 2001 (2%) than in 1996 (9%) and 1982 (0%) (Chi-square for trend p = 0.016). The proportion of girls with no regular partner who considered protection from sexually transmitted disease important for their choice of contraception was 39% in 2001 compared with 71% in 1996 and only 10% in 1982 (Chi-square for trend: p < 0.0001). Boys: More boys reported sexual debut before their 16th birthday in 2001 (40%) than in 1996 (37%) and 1982 (24%) (Chi-square for trend: p = 0.023). For boys with no regular partner, condom was preferred for personal protection by 85% in 2001, 91% in 1996 and 61% in 1982 (Chi-square for trend p = 0.007). Protection against sexually transmitted infection declined, especially among boys with no regular partner, from 51% in 2001 to 72% in 1996 and 21% in 1982 Chi-square for trend: p < 0.0001). The tendency towards earlier sexual debut and less use of safe sex practices to protect against sexually transmitted infections (STI) was accompanied by a rise in the number of detected STIs during this period. CONCLUSIONS: The period from 1982 to 1996 during which sexual attitudes were directed toward safer sex seems to have given way to a reverse trend in the period from 1996 to 2001. These findings may have significant implications for health care authorities organising preventive strategies for healthy adolescents

Culture, technology and local networks: towards a sociology of ‘making’ in education

This article is about ‘making’ in education. Often associated with software programming (as in ‘digital making’), making can also involve creating or modifying physical technological artefacts. In this paper, making is examined as a phenomenon that occurs at the intersection of culture, the economy, technology and education. The focus is not on the effects on cognitive gains or motivations, but on locating making in a social, historical and economic context. Making is also described as a form of ‘material connotation’, where connotation refers to the process through which the technical structure of artefacts is altered by culture and society. In the second part of the paper, the theoretical discussion is complemented by a case study in which making is described as a networked phenomenon where technology companies, consultants, volunteers, schools, and students were all implicated in turning a nebulous set of practices and discourses into an educational reality

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research