Multidimensional Effects of Stress on Neuronal Exosome Levels and Simultaneous Transcriptomic Profiles.

Background: An excess of exosomes, nanovesicles released from all cells and key regulators of brain plasticity, is an emerging therapeutic target for stress-related mental illnesses. The effects of chronic stress on exosome levels are unknown; even less is known about molecular drivers of exosome levels in the stress response.

Methods: We used our state-of-the-art protocol with 2 complementary strategies to isolate neuronal exosomes from plasma, ventral dentate gyrus, basolateral amygdala, and olfactory bulbs of male mice to determine the effects of chronic restraint stress (CRS) on exosome levels.

The hostile environment in primary care: Qualitative analysis of a cross sectional survey of health care professionals in primary care.

Background: In 2014 the UK government rolled out the then called hostile environment as a series of punitive policies designed to disenfranchise undocumented migrants from living in Britain. As part of these measures upfront charging was introduced in 2017 which saw patients being denied treatment without prior full payment based on their immigration status.

Aim: Assess the knowledge of the charging regulations in a sample of primary care practitioners.

Simulation-based research for digital health pathologies: A multi-site mixed-methods study.

Background: The advance of digital health technologies has created new forms of potential pathology which are not captured in current clinical guidelines. Through simulation-based research, we have identified the challenges to clinical care that emerge when patients suffer from illnesses stemming from failures in digital health technologies.

Methods: Clinical simulation sessions were designed based on patient case reports relating to (a) medical device hardware errors, (b) medical device software errors, (c) complications of consumer technology and (d) technology-facilitated abuse.

Medical consequences of "contingency accommodation" for people seeking asylum: thematic analysis of a survey from professionals working in contingency accommodation.

Background: Concerns about the housing of migrants and asylum seekers have escalated since the COVID-19 pandemic. From the use of quasi-detention facilities and so-called contingency accommodation to outbreaks of diphtheria in processing centres, there is a worrying trend to normalise potentially damaging conditions. The aim of this study was to assess the health risks posed by contingency housing for asylum seekers in the UK.

Interventions to improve access to primary care for inclusion health groups in England: a scoping review.

Background: Everyone in England has the right to primary care without financial charges. Nevertheless, evidence shows that barriers remain for inclusion health populations such as vulnerable migrants, people experiencing homelessness, Gypsy, Roma, and Traveller (GRT) communities, and people who sell sex. There is little evidence for what works to improve access.

Epigenetic embedding of childhood adversity: mitochondrial metabolism and neurobiology of stress-related CNS diseases.

This invited article ad memoriam of Bruce McEwen discusses emerging epigenetic mechanisms underlying the from adverse childhood experiences to adult physiology and brain functions. The conceptual framework that we pursue suggest multidimensional biological pathways for the rapid regulation of neuroplasticity that utilize rapid non-genomic mechanisms of epigenetic programming of gene expression and modulation of metabolic function via mitochondrial metabolism. The current article also highlights how applying computational tools can foster the translation of basic neuroscience discoveries for the development of novel treatment models for mental illnesses, such as depression to slow the clinical manifestation of Alzheimer's disease.

Mechanisms for the prevention of adolescent intimate partner violence: A realist review of interventions in low- and middle-income countries.

Adolescent girls are among those at the greatest risk of experiencing intimate partner violence (IPV). Despite adolescence being widely regarded as a window of opportunity to influence attitudes and behaviours related to gender equality, evidence on what works to prevent IPV at this critical stage is limited outside of high-income, school-based settings. Even less is understood about the mechanisms of change in these interventions.

Pregnancy-Related Tuberculous Meningitis and Immune Reconstitution Inflammatory Syndrome: A Case Series and Systematic Review.

Background: Tuberculosis is a leading cause of death among women of reproductive age. However, tuberculous meningitis, the most severe form of extrapulmonary tuberculosis, is rarely discussed in pregnancy despite this being a unique period of immune modulation that may predispose women to active disease.

Methods: We identified and described cases of tuberculous meningitis among pregnant or postpartum women screened during meningitis clinical trials in Uganda from 2018 to 2022.

Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes.

Major depressive disorder (MDD) is a primary psychiatric illness worldwide; there is a dearth of new mechanistic models for the development of better therapeutic strategies. Although we continue to discover individual biological factors, a major challenge is the identification of integrated, multidimensional traits underlying the complex heterogeneity of depression and treatment outcomes. Here, we set out to ascertain the emergence of the novel mitochondrial mediator of epigenetic function acetyl-L-carnitine (LAC) in relation to previously described individual predictors of antidepressant responses to the insulin-sensitizing agent pioglitazone.

Charging of overseas visitors in England and universal health coverage: a cross-sectional analysis of NHS trusts.

Background: In 2017, new regulations in England introduced upfront charging for non-urgent care within the National Health Service (NHS). Individuals from outside the European Economic Area who have not paid the immigration surcharge are chargeable for NHS care at 150% of cost.

Methods: A freedom of information (FOI) request was sent to 135 acute non-specialist NHS trusts in England to create a database of overseas visitors charges.

A Journey of Hope: giving research participants a voice to share their experiences and improve community engagement around advanced HIV disease in Uganda.

Over the last decade excellent progress has been made globally in HIV management thanks to antiretroviral therapy (ART) rollout and international guidelines now recommending immediate initiation of ART in people living with HIV. Despite this, advanced HIV disease (CD4 less than 200 cells/mL) and opportunistic infections remain a persistent challenge and contribute significantly to HIV-associated mortality, which equates to 23,000 deaths in Uganda in 2018 alone. Our Meningitis Research Team based in Uganda is committed to conducting clinical trials to answer important questions regarding diagnostics and management of HIV-associated opportunistic infections, including tuberculosis and cryptococcal meningitis.

Treatment Outcomes in Adult Tuberculous Meningitis: A Systematic Review and Meta-analysis.

Background: There is substantial variation in the reported treatment outcomes for adult tuberculous meningitis (TBM). Data on survival and neurological disability by continent and HIV serostatus are scarce.

Methods: We performed a systematic review and meta-analysis to characterize treatment outcomes for adult TBM.

Insulin receptor substrate in brain-enriched exosomes in subjects with major depression: on the path of creation of biosignatures of central insulin resistance.

Insulin signaling is critical for neuroplasticity, cerebral metabolism as well as for systemic energy metabolism. In rodent studies, impaired brain insulin signaling with resultant insulin resistance (IR) modulates synaptic plasticity and the corresponding behavioral functions. Despite discoveries of central actions of insulin, in vivo molecular mechanisms of brain IR until recently have proven difficult to study in the human brain.

Tuberculosis in HIV-Associated Cryptococcal Meningitis is Associated with an Increased Risk of Death.

Tuberculosis (TB) and cryptococcal meningitis are leading causes of morbidity and mortality in advanced HIV disease. Data are limited on TB co-infection among individuals with cryptococcal meningitis. We performed a retrospective analysis of HIV-infected participants with cryptococcal meningitis from 2010-2017.

Multidimensional Predictors of Susceptibility and Resilience to Social Defeat Stress.

Background: Previous studies identified several separate risk factors for stress-induced disorders. However, an integrative model of susceptibility versus resilience to stress including measures from brain-body domains is likely to yield a range of multiple phenotypic information to promote successful adaptation to stress.

Methods: We used computational and molecular approaches to test whether 1) integrative brain-body behavioral, immunological, and structural domains characterized and predicted susceptibility or resilience to social defeat stress (SDS) in mice and 2) administration of acetyl-L-carnitine promoted resilience at the SDS paradigm.

Sotos Syndrome Presenting with Neonatal Hyperinsulinaemic Hypoglycaemia, Extensive Thrombosis, and Multisystem Involvement.

Initially described as an uncommon presenting feature of Sotos syndrome (SoS), over the last decades, congenital hyperinsulinaemic hypoglycaemia (CHI) has been increasingly reported in association with this condition. The mechanism responsible for CHI in SoS is unclear. We report the case of a neonate presenting with CHI and extensive venous and arterial thrombosis associated with kidney, heart, liver, skeleton, and brain abnormalities and finally diagnosed with SoS on whole genome sequencing.