The role of a Medical Examiner Service in an acute NHS hospital: Perspectives from doctors and next of kin.

A new Medical Examiner system was introduced in England and Wales in 2019 to scrutinise all non-coronial deaths. The three key roles of independent Medical Examiner scrutiny are to establish accurate causes of death, determine whether coronial referral is required and identify any care concerns. This is the first published service evaluation exploring the views of doctors and next of kin with whom Medical Examiner Services interact. The aims were to understand whether the Medical Examiner Service was achieving its three main roles. Surveys were sent electronically to the qualified attending practitioners, and by post to the next of kin, of a consecutive series of deceased patients reviewed by an acute NHS hospital Medical Examiner Service in the East of England. Recruitment took place over a five month period in 2023. Results are based on 100 returned surveys from doctors (response rate 35%) and 179 completed by next of kin (response rate 65%). Findings suggest the Medical Examiner Service was successfully achieving its three key roles and well received by both doctors and next of kin. Service user feedback is clearly important as Medical Examiner Services continue to develop into the statutory phase during 2024, when they are anticipated to review approximately 400,000 deaths per annum in England and Wales. This study demonstrates such feedback is not only useful for service development, but also eminently possible.

The workload of a medical examiner service at an acute National Health Service hospital during the COVID-19 pandemic: The Norfolk & Norwich University Hospital experience.

The COVID-19 pandemic commenced in March 2020. In May 2019, a new Medical Examiner system was introduced to scrutinise deaths of patients dying within acute National Health Service Trusts. The Coronavirus Act 2020 which came into force in March 2020 modified certification of death requirements. Newly formed Medical Examiner Services were advised they could suspend scrutiny during the pandemic. The Norfolk & Norwich University Hospital Medical Examiner Service (NNUH MES) continued to scrutinise patient deaths throughout. This study summarises the workload of the NNUH MES from 1st June 2020 to 31st May 2021 over which period 2856 deaths were recorded and 2687 scrutinised by the Medical Examiners.

A meta-analysis and critical review of metacognitive accuracy in autism.

LAY ABSTRACT: The ability to make accurate judgements about our own and others' mental states has been widely researched; however, it is unclear how these two abilities relate to each other. This is important given that there is evidence that autistic individuals can have difficulty with accurately judging others' mental states. Recent evidence suggests that some autistic individuals may also have difficulty accurately judging their own mental states. This may have an impact on various aspects of everyday life but particularly academic success, and therefore it is important that this skill is not overlooked when exploring areas of individual support. The aim of this article is to bring together the research examining autistic individual's ability of making accurate judgements about their own mental states and to establish whether this is an area that warrants further investigation. The results from this article show that autistic individuals may have difficulty making accurate judgements about their own mental states, although this depends on the type of judgement being made. It also highlighted that while autistic children may have difficulties in some areas, these may improve by adulthood. Overall, this article shows that more research is needed to fully understand where specific difficulties lie and how they may be overcome.

Acute Effect of Height-Adjustable Workstations on Blood Glucose Levels in Women With Impaired Fasting Glucose Levels While Working: A Pilot Study.

Objective: To examine the effect on continuously monitored blood glucose (CGM) among participants with impaired fasting glucose (IFG) who used a height-adjustable desk while working. Methods: The study was a repeated measures pilot study in overweight or obese women who had IFG (blood glucose [BG] >100 mg/dL) and a sedentary job. Blood glucose was monitored with CGM devices during two 1-week periods at work; 1 week in the seated position and 1 week using alternate bouts of sitting and standing (by adjusting their desks) throughout the workday. Results: Ten women completed the study. Sedentary time significantly predicted BG independently of diet and overall physical activity (P=.02). Dietary carbohydrates, protein, and fat were significant predictors of BG (P<.001). Conclusions: Sedentary time is a strong predictor of increased BG in women with IFG and a sedentary job.

The athletic gut microbiota.

The microorganisms in the gastrointestinal tract play a significant role in nutrient uptake, vitamin synthesis, energy harvest, inflammatory modulation, and host immune response, collectively contributing to human health. Important factors such as age, birth method, antibiotic use, and diet have been established as formative factors that shape the gut microbiota. Yet, less described is the role that exercise plays, particularly how associated factors and stressors, such as sport/exercise-specific diet, environment, and their interactions, may influence the gut microbiota. In particular, high-level athletes offer remarkable physiology and metabolism (including muscular strength/power, aerobic capacity, energy expenditure, and heat production) compared to sedentary individuals, and provide unique insight in gut microbiota research. In addition, the gut microbiota with its ability to harvest energy, modulate the immune system, and influence gastrointestinal health, likely plays an important role in athlete health, wellbeing, and sports performance. Therefore, understanding the mechanisms in which the gut microbiota could play in the role of influencing athletic performance is of considerable interest to athletes who work to improve their results in competition as well as reduce recovery time during training. Ultimately this research is expected to extend beyond athletics as understanding optimal fitness has applications for overall health and wellness in larger communities. Therefore, the purpose of this narrative review is to summarize current knowledge of the athletic gut microbiota and the factors that shape it. Exercise, associated dietary factors, and the athletic classification promote a more "health-associated" gut microbiota. Such features include a higher abundance of health-promoting bacterial species, increased microbial diversity, functional metabolic capacity, and microbial-associated metabolites, stimulation of bacterial abundance that can modulate mucosal immunity, and improved gastrointestinal barrier function.

Probiotic Supplementation Has a Limited Effect on Circulating Immune and Inflammatory Markers in Healthy Adults: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: A main mechanism of action proposed for oral probiotic supplementation is immunomodulation, which is expected to impart health benefits in the host by influencing circulating immune and inflammatory factors. To date, the effectiveness of probiotic supplementation for immunomodulation in healthy adults without disease has not been evaluated in a systematic review. OBJECTIVE: The objective of this systematic review was to evaluate the effect of probiotic supplementation on circulating immune and inflammatory markers of healthy adults compared to placebo. METHODS: PubMed, SCOPUS, ISI Web of Science, ProQuest, and Cochrane databases were searched for English articles up to May 15, 2019. Additional papers were identified by checking references of relevant papers. Only randomized controlled trials studying the administration of probiotic supplements compared to placebo on immune and inflammatory markers in healthy adults (aged 18 to 65 years), without acute or chronic disease, and in generally good health were examined. Independent extraction of articles was conducted by two authors using predefined search terms and restrictions/filters. The methodologic quality of each study was appraised using the Academy of Nutrition and Dietetics Evidence Analysis Library Quality Rating Worksheet and the body of evidence was assessed using the Academy of Nutrition and Dietetics Grade Definitions and Conclusion Grading Table. RESULTS: Eighteen articles, including 819 subjects, met eligibility criteria and were included in the present systematic review. Five articles were rated neutral in quality and 13 were rated high in quality. Eight articles reported a significant effect on immune and/or inflammatory parameters including increases in natural killer cells, lymphocytes, and monocytes, and decreases in proinflammatory cytokine concentrations. CONCLUSIONS: Based on the 18 articles extracted in this systemic review, probiotic supplementation was concluded to have a limited effect on immune and inflammatory markers in healthy adults. Overall, the evidence was heterogenous, precluding a meta-analysis, and difficult to aggregate and conclude on effect size. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO ref CRD42018110856.

International Society of Sports Nutrition Position Stand: Probiotics.

Position statement: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of probiotic supplementation to optimize the health, performance, and recovery of athletes. Based on the current available literature, the conclusions of the ISSN are as follows: 1)Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (FAO/WHO).2)Probiotic administration has been linked to a multitude of health benefits, with gut and immune health being the most researched applications.3)Despite the existence of shared, core mechanisms for probiotic function, health benefits of probiotics are strain- and dose-dependent.4)Athletes have varying gut microbiota compositions that appear to reflect the activity level of the host in comparison to sedentary people, with the differences linked primarily to the volume of exercise and amount of protein consumption. Whether differences in gut microbiota composition affect probiotic efficacy is unknown.5)The main function of the gut is to digest food and absorb nutrients. In athletic populations, certain probiotics strains can increase absorption of key nutrients such as amino acids from protein, and affect the pharmacology and physiological properties of multiple food components.6)Immune depression in athletes worsens with excessive training load, psychological stress, disturbed sleep, and environmental extremes, all of which can contribute to an increased risk of respiratory tract infections. In certain situations, including exposure to crowds, foreign travel and poor hygiene at home, and training or competition venues, athletes' exposure to pathogens may be elevated leading to increased rates of infections. Approximately 70% of the immune system is located in the gut and probiotic supplementation has been shown to promote a healthy immune response. In an athletic population, specific probiotic strains can reduce the number of episodes, severity and duration of upper respiratory tract infections.7)Intense, prolonged exercise, especially in the heat, has been shown to increase gut permeability which potentially can result in systemic toxemia. Specific probiotic strains can improve the integrity of the gut-barrier function in athletes.8)Administration of selected anti-inflammatory probiotic strains have been linked to improved recovery from muscle-damaging exercise.9)The minimal effective dose and method of administration (potency per serving, single vs. split dose, delivery form) of a specific probiotic strain depends on validation studies for this particular strain. Products that contain probiotics must include the genus, species, and strain of each live microorganism on its label as well as the total estimated quantity of each probiotic strain at the end of the product's shelf life, as measured by colony forming units (CFU) or live cells.10)Preclinical and early human research has shown potential probiotic benefits relevant to an athletic population that include improved body composition and lean body mass, normalizing age-related declines in testosterone levels, reductions in cortisol levels indicating improved responses to a physical or mental stressor, reduction of exercise-induced lactate, and increased neurotransmitter synthesis, cognition and mood. However, these potential benefits require validation in more rigorous human studies and in an athletic population.

Putting Your Money Where Your Mouth is: Examining Metacognition in ASD Using Post-decision Wagering.

It has been argued that metacognition and mindreading rely on the same cognitive processes (Carruthers in The opacity of mind: an integrative theory of self-knowledge, Oxford University Press, Oxford, 2011). It is widely accepted that mindreading is diminished among individuals diagnosed with autism (Brunsdon and Happé in Autism 18(1):17-30, 2014), however, little is known about metacognition. This study examined metacognition in relation to mindreading and autism using post-decision wagering. Results from a student sample showed negative associations between autism traits and metacognitive accuracy, and metacognitive reaction times and mindreading. These findings were replicated in a general population sample, providing evidence of a reliable association between metacognition, mindreading and autism traits. However, adults diagnosed with autism showed equivalent levels of metacognitive accuracy to age- and IQ-matched comparison participants, albeit only with an overall increase in meta-level processing time.

Interoception is Impaired in Children, But Not Adults, with Autism Spectrum Disorder.

Interoception (the ability to sense what's going on inside one's body) is considered integral to many higher-order cognitive processes. Some have speculated that impaired interoception may underpin some features of ASD. Yet, in Experiment 1, we found no evidence of a between-group difference in either cardiac or respiratory interoceptive accuracy among 21 adults with ASD and 21 matched controls. Bayesian analyses suggested the data strongly supported the null hypothesis. In Experiment 2, we measured cardiac interoceptive accuracy in 21 children with ASD and 21 matched controls. Here interoceptve accuracy was significantly diminished in the ASD group and was associated with a moderate-to-large effect size. Results suggest early interoception difficulties are resolved or compensated for by adulthood in people with ASD.

Do Heavier Patients With Adolescent Idiopathic Scoliosis Have More Preserved Thoracic Kyphosis and Pulmonary Function?

STUDY DESIGN: Retrospective. OBJECTIVES: We aimed to determine if heavier patients with adolescent idiopathic scoliosis (AIS) had more preserved thoracic kyphosis (TK), and as a result, more preserved pulmonary function. SUMMARY OF BACKGROUND DATA: Some believe that childhood weight is predictive of adult sagittal plane parameters, with heavier children having greater TK as adults. Generally, thoracic scoliosis is coupled with loss of TK, which is associated with worsening pulmonary function. METHODS: A total of 142 patients with AIS and a structural main thoracic curve were analyzed. We excluded patients with structural proximal thoracic curves (Lenke 2 and 4). Standing preoperative radiographs, pulmonary function tests, and preoperative body mass indices (BMIs) were reviewed. The main thoracic Cobb angle, T2-T12 TK, percentage predicted forced vital capacity (FVC) and BMI were recorded. Spearman correlation was determined. Linear regression analysis used FVC as the primary outcome and BMI, TK, and Cobb angle as the independent variables. BMI categories were overweight/obese (BMI ≥25) and normal (BMI <25). Wilcoxon rank-sum tests were performed to detect a difference in TK and BMI between the 2 groups. The Cobb angles between the two groups were analyzed by t tests. RESULTS: Demonstrated correlations included BMI and FVC (0.37, p ≤.01), FVC and TK (0.26, p <.01), BMI and TK (0.23, p = .01), and FVC and Cobb angle (-0.23, p = .01). Linear regression revealed that Cobb angle (p ≤.01), TK (p <.01), and BMI (p <.01) remained statistically significant predictors of FVC. Wilcoxon rank-sum tests revealed a statistically significant difference between TK (p = .03) and FVC (p <.01) in the overweight/obese group and the normal group, with the overweight/obese group having greater values for both TK and FVC. The Cobb angles between the overweight/obese and normal group were not significantly different (p = .72). CONCLUSIONS: Heavier AIS patients have greater values of TK and percentage predicted FVC. LEVEL OF EVIDENCE: Level III.

Parenting a Child with Phenylketonuria (PKU): an Interpretative Phenomenological Analysis (IPA) of the Experience of Parents.

Phenylketonuria (PKU) is a rare inherited metabolic disorder which can cause neurological damage if left untreated. PKU is identified through newborn screening in developed countries, and treatment begins immediately to prevent these severe consequences. When a child is diagnosed, parents must assume immediate responsibility for the management of PKU and prevention of neurological damage. Quantitative studies have identified significant psychosocial stressors for parents, but little is known about how the parents experience this process. This study aimed to explore the experiences of parents of children with PKU under the age of two. It is the first study to examine these experiences in this way. Seven parents were interviewed about their experiences, and interpretative phenomenological analysis was used to analyse the data. Three main themes were identified: control, striving for normality and acceptance of PKU as a continuum. Links between the themes and processes underpinning the results were explored with relation to existing literature and theories from a clinical psychology perspective. The role of acceptance of PKU was central to the parent's experiences. Clinical implications and suggestions for further research are discussed.

Sedentary Behaviors and Cardiometabolic Risk: An Isotemporal Substitution Analysis.

Evidence suggests that time spent engaging in sedentary behaviors is associated with a greater risk of adverse cardiometabolic outcomes. We investigated the cross-sectional associations of 6 unique sedentary tasks (watching television, using the computer, completing paperwork, reading, talking on the telephone, and sitting in a car) with cardiometabolic risk factors, and also examined the effect of replacing one type of sedentary behavior with another on the level of cardiometabolic risk. Participants consisted of 3,211 individuals from the Coronary Artery Risk Development in Young Adults Study who visited the clinic between 2010 and 2011. Linear regression models examined the independent and joint associations of sedentary tasks with a composite cardiometabolic risk score, as well as with individual cardiometabolic risk factors (waist circumference, blood pressure, fasting glucose, insulin, triglycerides, and high density lipoprotein cholesterol) after adjusting for physical activity and other covariates. Replacing 2 hours of television viewing with 2 hours spent performing any other sedentary activity was associated with a lower cardiometabolic risk score of 0.06-0.09 standard deviations (all 95% confidence intervals: -0.13, -0.02). No other replacements of one type of sedentary task for another were significant. Study findings indicate that television viewing has a more adverse association with cardiometabolic risk factors than other sedentary behaviors.

Oral Supplementation with Baker's Yeast Beta Glucan Is Associated with Altered Monocytes, T Cells and Cytokines following a Bout of Strenuous Exercise.

Exercise and physical labor in extreme environmental conditions causes transient decreases in immune cell and cytokine concentrations, likely increasing the susceptibility to opportunistic infection. Baker's yeast beta glucan (BYBG) has been previously demonstrated to be an effective countermeasure in athletes, but its effectiveness in individuals of average fitness under similar physical stress is unknown. The purpose of this study was to determine if 10 days of oral supplementation with BYBG could modify previously observed suppression of monocytes, T cells, circulating and whole blood LPS-stimulated cytokines due to strenuous exercise. Venous blood samples were collected from 109 healthy volunteers prior to, immediately after, 2 and 4 h post-exercise. Monocyte and T cell concentration, cell-surface receptor expression and serum and LPS-stimulated cytokines were assessed. BYBG significantly (P < 0.05) altered total and classic monocyte concentration and expression of CD38, CD80, CD86, TLR2, and TLR4 on monocyte subsets. BYBG also significantly increased CD4+ and CD8+ T cell concentration and the exercise response of CCR7+/CD45RA- central memory (TCM) cells. Likewise, BYBG significantly (P < 0.05) altered serum IFN-γ and IL-2, and LPS-stimulated IFN-γ, IL-2, IL-4, and IL-7. Taken together these data support the hypothesis that oral BYBG supplementation modulates the expected exercise response for individuals of average fitness. This may result in a decrease in susceptibility to opportunistic infections after strenuous exercise.

Treatment Adherence and Psychological Wellbeing in Maternal Carers of Children with Phenylketonuria (PKU).

Phenylketonuria (PKU), a rare metabolic disorder, causes cognitive impairment unless treated with a strict, protein-restricted diet, but few studies have examined the relationship between treatment compliance and parental wellbeing. In the present study, 46 primary caregivers of children with PKU completed measures of psychological distress, parenting stress (related to caring for a child with an illness), resilience, perceived social support and child dependency. Treatment adherence was assessed using the proportion of blood phenylalanine concentrations within target range in the preceding year. Results indicated that 59% of caregivers showed clinical levels of psychological distress, which was predicted by their parenting stress and resilience. Whilst the proportion of blood phenylalanine concentrations in range was not associated with parental distress, it was predicted by child age and caregiver's perceived support from family. Despite experiencing high levels of distress, the results indicated that caregivers' ability to adhere to treatment was not affected. Interventions to reduce parenting stress and boost caregiver resilience may have a positive effect on parental wellbeing. Additionally, interventions to promote treatment adherence benefit parents of older children, with a focus on promoting support from family members. Further research with larger sample sizes and longitudinal designs is needed to further establish causal mechanisms.

Baker's yeast beta glucan supplementation increases salivary IgA and decreases cold/flu symptomatic days after intense exercise.

Strenuous exercise, such as running a marathon, is known to suppress mucosal immunity for up to 24 hr, which can increase the risk of developing an upper respiratory tract infection (URTI) and reduced performance capacity (Allgrove JE, Geneen L, Latif S, Gleeson M. Influence of a fed or fasted state on the s-IgA response to prolonged cycling in active men and women. Int J Sport Nutr Exerc Metab. 2009;19(3):209-221; Barrett B, Locken K, Maberry R, Schwamman J, Brown R, Bobula J, Stauffacher EA. The Wisconsin Upper Respiratory Symptom Survey (WURSS): a new research instrument for assessing the common cold. J Fam Pract. 2002;51(3):265; Carpenter KC, Breslin WL, Davidson T, Adams A, McFarlin BK. Baker's yeast beta glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk? Br J Nutr. 2012;1-9). While many dietary interventions have been used to combat postexercise immune suppression, most have been ineffective. The key purpose of this study was to determine if baker's yeast ß-glucan (BG) could positively affect the immune system of individuals undergoing intense exercise stress using two experiments. In the first (E1; N = 182 men and women), BG was compared to placebo supplementation for the incidence of URTI symptoms for 28 days postmarathon. In the second (E2; N = 60 men and women) changes in salivary immunoglobulin A (IgA) were evaluated after 50-min of strenuous cycling when participants had been supplemented for 10 days with either BG (250 mg/day) or placebo (rice flour). For E1, subjects reported URTI symptoms using a daily health log. For E2, saliva was collected prior to, immediately, and 2-hr postexercise using a salivette. Data for E1 and E2 were analyzed using separate analyses of variance (ANOVAs) with repeated measures (p < .05). In E1, BG was associated with a 37% reduction in the number of cold/flu symptom days postmarathon compared to placebo (p = .026). In E2, BG was associated with a 32% increase in salivary IgA (p = .048) at 2 hr after exercise compared to placebo. In summary, the present study demonstrates that BG may reduce URTI symptomatic days and improve mucosal immunity (salivary IgA) postexercise.

A one-year school-based diet/exercise intervention improves non-traditional disease biomarkers in Mexican-American children.

School-based interventions are an effective way to treat childhood obesity. The purpose of the present study was to biologically validate an established school-based intervention designed to reduce standardised body mass index (zBMI) over a period of 12 months. This intervention focused on a subset of Mexican-American children who were participating in a larger clinical weight loss study. Plasma samples were analysed from self-identified Mexican-American children (12-14 years) who were randomised to either a school-based intervention (IN, n = 152) or self-help control (CN, n = 69). Treatment was 4 days week⁻¹ of exercise (45 min day⁻¹) and 1 day week⁻¹ of nutritional counselling for 6 months. Fasting (>8 h) blood samples were collected at baseline, 6 months (end of active intervention) and 12 months (6 months after the end of the active intervention). Plasma resistin, adiponectin and leptin concentration were measured using a multiplex assay. Separate linear mixed models and a P < 0.05 were used to test for significance. Significant group × time interactions were found for resistin (P < 0.0001), adiponectin (P = 0.001) and leptin (P = 0.013). For resistin, IN was 12% lower at 6 months than CN. Adiponectin concentration in IN was greater at 6 months (26%) and 12 months (8%) than CN. Leptin concentration was 22% lower for IN at 12 months than CN. We have previously reported that our school-based intervention reduced zBMI and now reported alterations in biologically relevant disease biomarkers. Some of the observed changes were only present at the end of the active intervention (resistin), while others persisted until 12 months (leptin and adiponectin). These changes underscore the effectiveness of our school-based intervention at not only improving zBMI but also at reducing disease risk.

Obese Mexican American children have elevated MCP-1, TNF-α, monocyte concentration, and dyslipidemia.

BACKGROUND AND OBJECTIVE: Obesity is an independent risk factor for chronic disease. The prevalence of obesity is especially high among Mexican American children. Peripheral blood monocytes are altered with obesity contributing to elevated systemic inflammation and increased risk of chronic disease. In addition, obesity alters the circulating levels of cytokines/chemokines that influence monocyte behavior. The study objective was to investigate alterations in blood monocytes and plasma cytokines/chemokine levels among healthy weight (standardized BMI [zBMI] ≤85th percentile; n = 66), overweight (zBMI 85th-95th percentile; n = 23), and obese (zBMI ≥95th percentile; n = 39) Mexican American children. METHODS: Blood samples were analyzed for total and subset monocyte concentration via flow cytometry. Serum monocyte chemoattractant protein-1 (MCP-1), fractalkine, interleukin-8, and tumor necrosis factor α (TNF-α) were measured by using a Milliplex MagPix assay. Serum cholesterol, high-density lipoproteins, triglycerides, and glucose were measured by using an enzymatic assay. RESULTS: Total monocyte concentration (P = .012), classic monocyte concentration (P = .045), MCP-1 (P = .015), and TNF-α (P = .002) were significantly greater in obese children compared with healthy weight children. Also, overweight and obese children had elevated triglycerides (P = .001) and reduced high-density lipoproteins (P = .033) compared with healthy weight children. CONCLUSIONS: Childhood obesity alters monocytes and circulating chemokines, putting children at a greater risk of developing obesity-related chronic diseases in adulthood. Further characterization of early immune alterations in childhood obesity may provide additional clinical insight into the assessment of obesity-related disease risk.

Moderate-intensity, premeal cycling blunts postprandial increases in monocyte cell surface CD18 and CD11a and endothelial microparticles following a high-fat meal in young adults.

High-fat meals promote transient increases in proatherogenic factors, implicating the postprandial state in cardiovascular disease (CVD) progression. Although low-grade inflammation is associated with CVD, little research has assessed postprandial inflammation. Because of its anti-inflammatory properties, premeal exercise may counteract postprandial inflammation. The purpose of this study was to determine postprandial alterations in monocytes and circulating markers of endothelial stress and inflammation following a high-fat meal in young adults with or without premeal cycle exercise. Each subject completed two trials and was randomized to rest or cycle at a moderate intensity prior to eating a high-fat meal. Flow cytometry was used to assess monocyte cell surface receptor expression and concentration of endothelial microparticles (EMP). Plasma cytokines were assessed using Luminex MagPix. Statistical analysis was completed using separate linear mixed models analyses with first-order autoregressive (AR(1)) heterogeneous covariance structure. Significance was set at P ≤ 0.05. Percentage increases in classic monocyte CD11a and CD18 were greater overall in the postprandial period in the meal-only condition compared with the meal + exercise condition (P < 0.05). EMP concentration was 47% greater 3 h after the meal compared with premeal values in the meal-only condition (P < 0.05); no significant increase was observed in the meal + exercise condition. Premeal cycling blunted postprandial increases in EMP and CD11a and CD18. Acute, moderate-intensity exercise may help counteract possibly deleterious postprandial monocyte and endothelial cell activation.

Aged mice have increased inflammatory monocyte concentration and altered expression of cell-surface functional receptors.

The expression of monocyte cell-surface receptors represents one index of immune dysfunction, which is common with aging. Although mouse models of aging are prevalent, monocyte subset assessment is rare. Our purpose was to compare cell receptor expression on classic (CD115+/Gr-1 high) and non-classic (CD115+/Gr-1 low) monocytes from 80- or 20-week-old CD-1 mice. Three-colour flow cytometry was used to determine the concentration of monocyte subsets and their respective cell-surface expression of TLR2, TLR4, CD80, CD86, MHC II and CD54. These receptors were selected because they have been previously associated with altered monocyte function. Data were analysed with independent t-tests; significance was set at P less than 0.05. Old mice had a greater concentration of both classic (258%, P=0.003) and non-classic (70%, P=0.026) monocytes. The classic : non-classic monocyte ratio doubled in old as compared with that in young mice (P=0.006), indicating a pro-inflammatory shift. TLR4 ( 27%, P=0.001) and CD80 ( 37%, P=0.004) were decreased on classic monocytes from old as compared with those from young mice. TLR2 ( 24%, P=0.002) and MHCII ( 21%, P=0.026) were altered on non-classic monocytes from old as compared with those from young mice. The increased classic : non-classic monocyte ratio combined with changes in the cell-surface receptor expression on both monocyte subsets is indicative of immune dysfunction, which may increase age-associated disease risk.

Effects of exercise on weight loss and monocytes in obese mice.

Obesity causes innate immune dysfunction, contributing to increased disease risk. Weight loss from a combination of caloric restriction and exercise is the most effective treatment of obesity. We compared forced and voluntary exercise as weight-loss treatments in diet-induced obese (DIO) mice and assessed the effects of weight loss on monocyte concentration and cell-surface expression of Toll-like receptor (TLR) 2, TLR4, CD80, and CD86. DIO CD1 male mice were allocated randomly to 1 of 3 groups (n = 6 per group): voluntary wheel running (VEX); forced treadmill running (FEX); and sedentary (S). A fourth (control) group (CN, n = 6) of nonDIO mice was included also. During the 8-wk weight-loss treatment, all 4 groups consumed a low-fat (10% fat) diet. Nonlethal saphenous vein blood samples collected at baseline, week 4, and week 8 were analyzed by flow cytometry to assess monocyte concentration and functional receptor expression. The VEX and FEX groups lost significantly more body weight (36% and 27%, respectively) over the 8 wk of treatment than did other groups. VEX mice ran 4.4 times more than did FEX animals. VEX mice had higher monocyte concentrations (48% and 58%, respectively) than did the CN and FEX groups. Compared with baseline, week 8 cell-surface expression of TLR2 (22%), TLR4 (33%), and CD86 (18%) was increased in VEX mice. At week 4, CD80 expression was 42% greater for VEX than S mice. The present study confirms that short-term exercise and low-fat diet consumption cause significant weight loss and altered immune profiles.