Collaborative and integrated working between general practice and community pharmacies: A realist review of what works, for whom, and in which contexts.

Objectives: Collaborative and integrated (C + I) working between general practice and community pharmacies has the potential to increase accessibility to services, improve service efficiency and quality of care, and reduce health care expenditures. Many existing studies report challenges and complexities inherent in establishing effective C + I ways of working. The aim of our review is to understand how, when and why working arrangements between General Practitioners (GP) and Community Pharmacists (CP) can provide the conditions necessary for effective communication, decision-making, and C + I working.

Myelin-reactive B cells exacerbate CD4 T cell-driven CNS autoimmunity in an IL-23-dependent manner.

B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein (MOG). Here, we show that upon immunization with the T cell-obligate autoantigen, MOG, IgH mice develop rapid and exacerbated experimental autoimmune encephalomyelitis (EAE) relative to wildtype (WT) counterparts, characterized by aggregation of T and B cells in the IgH meninges and by CD4 T helper 17 (Th17) cells in the CNS.

'Troubling' medication reviews in the context of polypharmacy and ageing: A linguistic ethnography.

Healthy ageing is a global priority. Polypharmacy (the use of 5+ medicines) amongst older people is increasing, with over one-third of adults in England, aged 80-89, prescribed at least eight medications. Although sometimes necessary, polypharmacy can be harmful; the risk of harm increases with age and number of medicines prescribed.

Providing care to marginalised communities: a qualitative study of community pharmacy teams.

Background: Health inequalities in the UK are widening, particularly since the COVID-19 pandemic. Community pharmacies are the most visited healthcare provider in England and are ideally placed to provide and facilitate access to care for those most disadvantaged.

Aim: To explore the experiences and needs of community pharmacy teams in providing care for marginalised groups and how this has changed since the COVID-19 pandemic.

Multimorbidity as chronic crisis: 'Living on' with multiple long-term health conditions in a socially disadvantaged London borough.

Contemporary health services are primarily designed around single diseases. People with multimorbidity (multiple long-term health conditions) often become burdened by accumulated treatments. Through multimodal fieldwork in a socially disadvantaged London borough, we explore how people living with multimorbidity navigate conditions of 'chronic crisis', encompassing ill-health, overmedicalisation, polypharmacy and social exclusion.

Advancing the communication of genetic risk for cardiometabolic diseases: a critical interpretive synthesis.

Background: Genetics play an important role in risk for cardiometabolic diseases-including type 2 diabetes, cardiovascular disease and obesity. Existing research has explored the clinical utility of genetic risk tools such as polygenic risk scores-and whether interventions communicating genetic risk information using these tools can impact on individuals' cognitive appraisals of disease risk and/or preventative health behaviours. Previous systematic reviews suggest mixed results.

CXCL10 Is Associated with Increased Cerebrospinal Fluid Immune Cell Infiltration and Disease Duration in Multiple Sclerosis.

Background: Cerebrospinal fluid (CSF) is an important sampling site for putative biomarkers and contains immune cells. CXCL10 is a multiple sclerosis (MS)-relevant chemokine that is present in the injured central nervous system and recruits CXCR3+ immune cells toward injured tissues.

Objective: Perform a comprehensive evaluation to determine a potential relationship between CXCL10 and various immune cell subsets in the CNS of MS and control cases.

Negotiating the polypharmacy paradox: a video-reflexive ethnography study of polypharmacy and its practices in primary care.

Background: Polypharmacy is an important safety concern. Medication reviews are recommended for patients affected by polypharmacy, but little is known about how they are conducted, nor how clinicians make sense of them. We used video-reflexive ethnography (VRE) to: illuminate how reviews are conducted; elicit professional dialogue and concerns about polypharmacy; invite new transferable understandings of polypharmacy and its management.

Community pharmacy and general practice collaborative and integrated working: a realist review protocol.

Introduction: Increasing collaborative and integrated working between General practice (GP) and Community pharmacy (CP) is a key priority of the UK National Health Service and has been proposed as a solution to reducing health system fragmentation, improving synergies and coordination of care. However, there is limited understanding regarding how and under which circumstances collaborative and integrated working between GP and CP can be achieved in practice and how regulatory, organisational and systemic barriers can be overcome.

Methods And Analysis: The aim of our review is to understand how, when and why working arrangements between GP and CP can provide the conditions necessary for optimal communication, decision-making, and collaborative and integrated working.

What do we want to get out of this? a critical interpretive synthesis of the value of process evaluations, with a practical planning framework.

Background: Process evaluations aim to understand how complex interventions bring about outcomes by examining intervention mechanisms, implementation, and context. While much attention has been paid to the methodology of process evaluations in health research, the value of process evaluations has received less critical attention. We aimed to unpack how value is conceptualised in process evaluations by identifying and critically analysing 1) how process evaluations may create value and 2) what kind of value they may create.

Investigating the NLRP3 inflammasome and its regulator miR-223-3p in multiple sclerosis and experimental demyelination.

Innate immune signaling pathways are essential mediators of inflammation and repair following myelin injury. Inflammasome activation has recently been implicated as a driver of myelin injury in multiple sclerosis (MS) and its animal models, although the regulation and contributions of inflammasome activation in the demyelinated central nervous system (CNS) are not completely understood. Herein, we investigated the NLRP3 (NBD-, LRR- and pyrin domain-containing protein 3) inflammasome and its endogenous regulator microRNA-223-3p within the demyelinated CNS in both MS and an animal model of focal demyelination.

Analysis of Plasma Using Flow Cytometry Reveals Increased Immune Cell-Derived Extracellular Vesicles in Untreated Relapsing-Remitting Multiple Sclerosis.

Extracellular vesicles (EVs) are secreted from cells under physiological and pathological conditions, and are found in biological fluids while displaying specific surface markers that are indicative of their cell of origin. EVs have emerged as important signaling entities that may serve as putative biomarkers for various neurological conditions, including multiple sclerosis (MS). The objective of this study was to measure and compare immune cell-derived EVs within human plasma between untreated RRMS patients and healthy controls.

Cytomegalovirus Immunity, Inflammation and Cognitive Abilities in the Elderly.

Reducing the socioeconomic toll from age-related physical and mental morbidities requires better understanding of factors affecting healthy aging. While many environmental, lifestyle, and genetic factors affect healthy aging, this study addressed the influence of cytomegalovirus (CMV) infection and immunity on age-related inflammation and cognitive abilities. Healthy adults 70-90 years old were recruited into a prospective study investigating relationships between anti-CMV immunity, markers of inflammation, baseline measures of cognitive ability, and changes in cognitive ability over 18 months.

Keeping in balance on the multimorbidity tightrope: A narrative analysis of older patients' experiences of living with and managing multimorbidity.

Primary care management of patients with multimorbidity in the UK is underpinned by clinical guidelines, quality standards and measurable targets which govern practices of risk management and disease control. There is concern that standardised approaches may not always be appropriate for older patients living with multimorbidity. Using a narrative approach, we elicited the voices of older people living with multiple conditions in order to rethink chronicity, and consider what their accounts might mean for reconfiguring care practices.

Organising polypharmacy: unpacking medicines, unpacking meanings-an ethnographic study.

Objectives: We explore how older patients affected by polypharmacy manage the 'hidden work' of organising their medicines, how they make sense of this work and integrate it into their lives.

Design And Setting: Ethnographic study observing patients over 18-24 months in patients' homes, general practice and community pharmacy, in England, UK.

Participants And Methods: Ethnographic case study including longitudinal follow-up of 24 patients aged 65 or older and prescribed ten or more items of medication.

Male sex chromosomal complement exacerbates the pathogenicity of Th17 cells in a chronic model of central nervous system autoimmunity.

Sex differences in multiple sclerosis (MS) incidence and severity have long been recognized. However, the underlying cellular and molecular mechanisms for why male sex is associated with more aggressive disease remain poorly defined. Using a T cell adoptive transfer model of chronic experimental autoimmune encephalomyelitis (EAE), we find that male Th17 cells induce disease of increased severity relative to female Th17 cells, irrespective of whether transferred to male or female recipients.

'It's all about patient safety': an ethnographic study of how pharmacy staff construct medicines safety in the context of polypharmacy.

Objective: As polypharmacy increases, so does the complexity of prescribing, dispensing and consuming medicines. Medication safety is typically framed as the avoidance of harm, achievable through adherence to policies, guidelines and operational standards. Automation, robotics and technologies are positioned as key players in the elimination of medication error in the face of escalating demand, despite limited research illuminating how these innovations are taken up, used and adapted in practice.

The impact of public involvement in health research: what are we measuring? Why are we measuring it? Should we stop measuring it?

As public involvement in the design, conduct and dissemination of health research has become an expected norm and firmly enshrined in policy, interest in measuring its impact has also grown. Despite a drive to assess the impact of public involvement, and a growing body of studies attempting to do just this, a number of questions have been largely ignored. This commentary addresses these omissions: What is the impact of all this focus on measuring impact? How is the language of impact shaping the debate about, and the practice of, public involvement in health research? And how have shifting conceptualisations of public involvement in health research shaped, and been shaped by, the way we think about and measure impact? We argue that the focus on impact risks distorting how public involvement in health research is conceptualised and practised, blinding us to possible negative impacts.

Addressing the polypharmacy challenge in older people with multimorbidity (APOLLO-MM): study protocol for an in-depth ethnographic case study in primary care.

Introduction: Polypharmacy is on the rise. It is burdensome for patients and is a common source of error and adverse drug reactions, especially among older adults. Health policy advises clinicians to practice -a person-centred approach to safe, effective medicines use.

Cytomegalovirus-Driven Adaption of Natural Killer Cells in NKG2C Human Immunodeficiency Virus-Infected Individuals.

Expansion of natural killer (NK) cells expressing NKG2C occurs following human cytomegalovirus (HCMV) infection and is amplified by human immunodeficiency virus (HIV) co-infection. These NKG2C-expressing NK cells demonstrate enhanced CD16-dependent cytokine production and downregulate FcεRIγ and promyelocytic leukemia zinc finger protein (PLZF). Lacking NKG2C diminishes resistance to HIV infection, but whether this affects NK cell acquisition of superior antibody-dependent function is unclear.

Proximity of Cytomegalovirus-Specific CD8 T Cells to Replicative Senescence in Human Immunodeficiency Virus-Infected Individuals.

Antiretroviral therapy (ART) effectively extends the life expectancy of human immunodeficiency virus (HIV)-infected individuals; however, age-related morbidities have emerged as major clinical concerns. In this context, coinfection with cytomegalovirus (CMV) accelerates immune senescence and elevates risk for other age-related morbidities, possibly through increased inflammation. We investigated potential relationships between CMV memory inflation, immune senescence, and inflammation by measuring markers of inflammation and telomere lengths of different lymphocyte subsets in HIV-infected individuals seropositive for anti-CMV antibodies.

NK cells generate memory-type responses to human cytomegalovirus-infected fibroblasts.

Natural killer (NK) cells are cytotoxic lymphocytes that selectively respond against abnormal cells. Human cytomegalovirus (HCMV) infection causes expansion of NKG2C CD57 NK cells in vivo and NKG2C NK cells proliferate when cultured with HCMV-infected cells. This raises the possibility of an NK-cell subset selectively responding against a specific pathogen and accruing memory.