Metabolite-sensing GPCRs controlling interactions between adipose tissue and inflammation.

Metabolic disorders including obesity, diabetes and non-alcoholic steatohepatitis are a group of conditions characterised by chronic low-grade inflammation of metabolic tissues. There is now a growing appreciation that various metabolites released from adipose tissue serve as key signalling mediators, influencing this interaction with inflammation. G protein-coupled receptors (GPCRs) are the largest family of signal transduction proteins and most historically successful drug targets. The signalling pathways for several key adipose metabolites are mediated through GPCRs expressed both on the adipocytes themselves and on infiltrating macrophages. These include three main groups of GPCRs: the FFA4 receptor, which is activated by long chain free fatty acids; the HCA2 and HCA3 receptors, activated by hydroxy carboxylic acids; and the succinate receptor. Understanding the roles these metabolites and their receptors play in metabolic-immune interactions is critical to establishing how these GPCRs may be exploited for the treatment of metabolic disorders.

Effects of Regular Physical Activity on the Immune System, Vaccination and Risk of Community-Acquired Infectious Disease in the General Population: Systematic Review and Meta-Analysis.

BACKGROUND: Regular physical activity is the prime modality for the prevention of numerous non-communicable diseases and has also been advocated for resilience against COVID-19 and other infectious diseases. However, there is currently no systematic and quantitative evidence synthesis of the association between physical activity and the strength of the immune system. OBJECTIVE: To examine the association between habitual physical activity and (1) the risk of community-acquired infectious disease, (2) laboratory-assessed immune parameters, and (3) immune response to vaccination. METHODS: We conducted a systemic review and meta-analysis according to PRISMA guidelines. We searched seven databases (MEDLINE, Embase, Cochrane CENTRAL, Web of Science, CINAHL, PsycINFO, and SportDiscus) up to April 2020 for randomised controlled trials and prospective observational studies were included if they compared groups of adults with different levels of physical activity and reported immune system cell count, the concentration of antibody, risk of clinically diagnosed infections, risk of hospitalisation and mortality due to infectious disease. Studies involving elite athletes were excluded. The quality of the selected studies was critically examined following the Cochrane guidelines using ROB2 and ROBINS_E. Data were pooled using an inverse variance random-effects model. RESULTS: Higher level of habitual physical activity is associated with a 31% risk reduction (hazard ratio 0.69, 95% CI 0.61-0.78, 6 studies, N = 557,487 individuals) of community-acquired infectious disease and 37% risk reduction (hazard ratio 0.64, 95% CI 0.59-0.70, 4 studies, N = 422,813 individuals) of infectious disease mortality. Physical activity interventions resulted in increased CD4 cell counts (32 cells/µL, 95% CI 7-56 cells/µL, 24 studies, N = 1112 individuals) and salivary immunoglobulin IgA concentration (standardised mean difference 0.756, 95% CI 0.146-1.365, 7 studies, N = 435 individuals) and decreased neutrophil counts (704 cells/µL, 95% CI 68-1340, 6 studies, N = 704 individuals) compared to controls. Antibody concentration after vaccination is higher with an adjunct physical activity programme (standardised mean difference 0.142, 95% CI 0.021-0.262, 6 studies, N = 497 individuals). CONCLUSION: Regular, moderate to vigorous physical activity is associated with reduced risk of community-acquired infectious diseases and infectious disease mortality, enhances the first line of defence of the immune system, and increases the potency of vaccination. PROTOCOL REGISTRATION: The original protocol was prospectively registered with PROSPERO (CRD42020178825).

Stroke secondary prevention, a non-surgical and non-pharmacological consensus definition: results of a Delphi study.

OBJECTIVE: Evidence supporting lifestyle modification in vascular risk reduction is limited, drawn largely from primary prevention studies. To advance the evidence base for non-pharmacological and non-surgical stroke secondary prevention (SSP), empirical research is needed, informed by a consensus-derived definition of SSP. To date, no such definition has been published. We used Delphi methods to generate an evidence-based definition of non-pharmacological and non-surgical SSP. RESULTS: The 16 participants were members of INSsPiRE (International Network of Stroke Secondary Prevention Researchers), a multidisciplinary group of trialists, academics and clinicians. The Elicitation stage identified 49 key elements, grouped into 3 overarching domains: Risk factors, Education, and Theory before being subjected to iterative stages of elicitation, ranking, discussion, and anonymous voting. In the Action stage, following an experience-based engagement with key stakeholders, a consensus-derived definition, complementing current pharmacological and surgical SSP pathways, was finalised: Non-pharmacological and non-surgical stroke secondary prevention supports and improves long-term health and well-being in everyday life and reduces the risk of another stroke, by drawing from a spectrum of theoretically informed interventions and educational strategies. Interventions to self-manage modifiable lifestyle risk factors are contextualized and individualized to the capacities, needs, and personally meaningful priorities of individuals with stroke and their families.

Objective assessment of intensity categorization of the previous day physical activity recall questionnaire in 11-13 year old children.

The Previous Day Physical Activity Recall (PDPAR) self-report questionnaire asks children to categories their time in 30 min blocks under activity codes and activity intensity (ActInt). Text and visual descriptors of ActInt are used which include posture and stepping intensity. This study aimed to objectively examine postures and stepping activity associated with PDPAR ActInt. Forty-three (19M/24F) 11-13 year children completed the PDPAR and wore a physical activity monitor (8 d). Within 30 min blocks the % sitting/lying, standing and stepping, steps, cadence and sit-to-stand transitions (STS) were examined by PDPAR ActInt across and within all activity codes. Data (14 083 30 min blocks) showed from light to moderate ActInt lower sedentary time, higher standing and stepping time, steps, sit-to-stand transitions and cadence (all P < 0.001). Between moderate and hard ActInt, time sedentary was lower and time stepping, steps and STS higher (all P < 0.005). No significant differences between hard and very hard. There was a wide variation of activity levels between activity codes within ActInt. ActInt within the PDPAR was not used consistently between activity codes. However, over all codes children demonstrated that they could distinguish between light and moderate and in some objective measures between moderate and hard, but not between hard and very hard ActInt.

Emotional and behavioral changes in parents of children affected by hemolytic-uremic syndrome associated with verocytotoxin-producing Escherichia coli: a qualitative analysis.

BACKGROUND: The long-term clinical outcome for children affected by hemolytic uremic syndrome associated with verocytotoxin-producing Escherichia coli (VTEC-HUS) is well documented, but the parental experience is not. OBJECTIVE: The authors investigated the effects of the critical-care hospitalization for this condition on well-being of patients' families. METHOD: A group of 30 parents completed a free-response format survey when their child presented to the hospital; 19 of this cohort completed a 1-year follow-up. RESULTS: Content analysis demonstrated that this cohort of parents experienced long-term emotional distress and substantive disruption to family and daily life. DISCUSSION: These results corroborate anecdotal clinical observations. The authors suggest future research initiatives and best practices to reduce parental distress.

Diary keeping and well-being.

In a pilot study, 177 female students completed a diary-keeping survey and measures of well-being. Diary keepers reported lower well-being than non-diary keepers.

The effects of guided written disclosure on psychological symptoms among parents of children with cancer.

This study examines whether structured writing about receiving a diagnosis and treatment for pediatric cancer reduces distress among highly distressed parents of children with cancer (PCWC). Eight PCWC completed measures of posttraumatic stress symptoms (PTSS) and depressive symptoms at two baselines, and again after writing, with 1-month gaps between assessments. Using a guided disclosure protocol (GDP), parents were asked to write about receiving the diagnosis first in a chronological manner, then to explicitly label their emotions at the time of diagnosis and explain the impact of the child's illness on their life. Finally, they were asked to reflect on current feelings, future coping ability, and personal growth. Although symptoms of distress did not change between baselines, significant reductions were found in PTSS from the first baseline to postwriting, but not in depression. This preliminary study suggests that the GDP may reduce PTSS in distressed PCWC.

Effects of guided written disclosure of stressful experiences on clinic visits and symptoms in frequent clinic attenders.

BACKGROUND: Psychosocial variables such as major stressful life events/daily stressful events have been associated with health care utilization. OBJECTIVE: Our aim was to examine the effects of a guided disclosure protocol (GDP) of past traumas on symptoms and clinic visits among frequent clinic attenders. METHODS: Forty-one frequent clinic attenders (> or =2 visits/3 months) took part. Patients were randomly assigned individually to either a casual content writing control group (n = 19) or a trauma content writing experimental GDP group (n = 22). GDP patients wrote about an upsetting event chronologically (day 1), verbally described their thoughts and feelings and described the event's impact on life (day 2), and finally wrote about their current perspective on and future coping with the event (day 3). Three months later, patients were reassessed blindly for symptoms and clinic visits, and an average of 15 months later they were assessed blindly for clinic visits again. RESULTS: Compared with controls, GDP patients reported lower symptom levels at 3 months (2.3 versus 5.2), and made fewer clinic visits during the 3 (1.3 versus 3.0) and 15 month (5.1 versus 9.7) follow-ups. The percentage of GDP patients making > or =10 visits during the 15 month follow-up was smaller (10%) than among controls (33%). CONCLUSIONS: The findings extend previous findings to frequent clinic users, using a new form of written disclosure aimed at shifting trauma from implicit to explicit memory. The GDP may be an inexpensive additional intervention in primary care for reducing symptoms and clinic visits among frequent clinic users.