Physical exercise, the immune system and infection risk: implications for prehabilitation and rehabilitation for solid organ transplantation candidates and recipients.

PURPOSE OF REVIEW: Solid organ transplantation recipients have an increased risk of infection, exacerbated by immunosuppressant medications that need to finely balance suppression of the immune system to prevent allograft rejection while avoiding over-suppression leading to infections and malignancy. Exercise modulates immune functions, with moderate-intensity activities particularly associated with enhanced antiviral immunity and reduced infection incidence. However, investigations of the effects of exercise and physical activity on immune function and infection risk posttransplantation are scarce. This review highlights areas where the relationship between exercise, immune function and infection risk has greatest potential for benefit for solid organ transplantation and therefore greatest need for investigation. RECENT FINDINGS: Moderate and higher intensity exercise do not appear to cause adverse immunological effects in kidney transplantation recipients, although evidence from other organ transplantation is lacking. Evidence from healthy younger and older adults suggests that regular exercise can reduce risk of respiratory infections and latent herpesvirus reactivation and improves antibody responses to vaccination, which is of great importance for organ transplantation recipients. SUMMARY: There is a strong need for research to investigate the role of exercise on immune function and infection risk in solid organ transplantation to improve both allograft survival and long-term health of the recipient.

Frequently Interrupting Prolonged Sitting With Light Body-Weighted Resistance Activity Alters Psychobiological Responses to Acute Psychological Stress: A Randomized Crossover Trial.

BACKGROUND: Uninterrupted prolonged sitting and exaggerated psychobiological reactivity to acute psychological stress are associated with increased risk of cardiovascular disease (CVD). Breaking up prolonged sitting with frequent, short bouts of light-intensity physical activity acutely lowers CVD risk markers under resting conditions. PURPOSE: To examine whether frequent interruptions to prolonged sitting with body-weighted resistance activity can acutely lower systolic blood pressure (SBP; primary outcome) and other cardiovascular (CV), inflammatory, and cortisol (secondary outcomes) responses to acute psychological stress. METHODS: This randomized crossover trial included 17 sedentary participants (9 men; mean ± SD age; 24.0 ± 0.5 years) who completed two conditions: (i) interrupting 4 hr of sitting with 4 min of light body-weighted resistance activity every 30-min (BREAK), and (ii) 4 hr of uninterrupted sitting (SIT). Following the BREAK and SIT intervention windows, CV, inflammatory, and cortisol markers were measured at rest, during stress tasks (8-min Paced Auditory Serial Addition Test [PASAT] and 3-min cold pressor [CP]), and 45-min recovery periods. RESULTS: There were main effects of time for CV parameters (SBP, diastolic blood pressure, heart rate, cardiac output, and total peripheral resistance [all p < .001]), inflammatory markers (interleukin-6 [IL-6]), and cortisol (p < .05) in response to stress. Time-by-condition interaction effects revealed that in the BREAK-condition there was lower SBP during immediate recovery from the CP (mean {95% confidence interval [CI]}: 127.2 [121.3, 133.4] vs 133.4 [125.5, 141.7] mmHg; p = .020), higher concentrations of plasma IL-6 45-min post-PASAT (2.70 [1.97, 3.70] vs 1.71 [1.32, 2.22] pg/mL; p = .010), and larger (nonsignificant) salivary cortisol concentrations 8-min post-CP (6.29 [4.60, 8.58] vs 3.97 [3.16, 4.99] nmol/L; p = .079). CONCLUSIONS: Interrupting prolonged sitting with frequent bouts of light intensity body-weighted resistance activity alters psychobiological responses to acute psychological stress. Further research should explore the longer-term implications for CVD risk.

Sitting for long periods without interruption and the way in which we physically respond to short-term psychological stress are linked to heart disease risk. Breaking up sitting with short, frequent bouts of light activity can lower heart disease risk but how this may improve how we respond to stress is unknown. Our study investigated if interruptions to prolonged sitting with body-weighted resistance activity lowered changes seen under stress such as changes in blood pressure (BP) and inflammation. Seventeen participants undertook two testing sessions. One session interrupted 4 hr of sitting with 4-min of light activity every 30-min, and the other session was 4 hr of uninterrupted sitting. After each session, participants did two stress tasks: one math-based task and one where feet were submerged in cold water. The changes in BP and inflammation to stress were measured. We found when breaking-up sitting time with activity, BP was lower after the cold-water task compared to when people did not break up their sitting. In summary, breaking up sitting with frequent bouts of light activity may influence how we respond to short-term stress, but future research needs to explore what these short-term changes mean for the longer-term risks of heart disease.

Mechanically demanding eccentric exercise increases nuclear factor erythroid 2-related factor 2 activity in human peripheral blood mononuclear cells.

PRE-REGISTRATION NUMBER: osf.io/kz37g.

Perceptions and Experiences of High-Intensity Interval Training in Kidney Transplant Recipients: A Big HIIT?

High-intensity interval training (HIIT) is considered a novel and time-efficient method to reduce cardiovascular disease risk, a leading cause of mortality in kidney transplant recipients. However, research in this population is severely limited. The aim of this study was to understand kidney transplant recipients' perceptions and experiences of HIIT and their readiness to participate in HIIT. Individual, semi-structured interviews were conducted in adults with a kidney transplant (n = 13; 53±13 years). Interviews were audiorecorded, transcribed verbatim, and subjected to framework analysis. Overall, participants had a good knowledge of HIIT and were open to participation. Acknowledgment of the superior benefits to cardiovascular, mental, and general health, as well as the lower time commitment, were all motivators for participation. There were some heightened concerns around damaging the kidney and 'knowing your limits. Personalization, physician's approval, and supervision were all important factors in participation. This study provides evidence that HIIT would be, in principle, largely accepted by recipients of a kidney transplant. However, several considerations are also identified in the present study, which would be essential to the success of any future efficacy trial or rehabilitation program.

Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis.

BACKGROUND: Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-α, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes. METHODS: Participants were randomized to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at a rating of perceived exertion of 12-14) in addition to usual care (n = 46) or usual care only (control group; n = 46). Outcome measures were obtained at baseline and then again at 6 months. RESULTS: There was no significant (P = 0.137) difference in circulating endotoxin between groups at 6 months (IDC group: 0.34 ± 0.08 EU/mL; control group: 0.37 ± 0.07 EU/mL). There were no significant between-group differences in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP and IL-6:IL-10 ratio. CONCLUSIONS: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.

Effect of high intensity interval training and moderate intensity continuous training on lymphoid, myeloid and inflammatory cells in kidney transplant recipients.

Kidney transplantations are seen to be a double-edge sword. Transplantations help to partially restore renal function, however there are a number of health-related co-morbidities associated with transplantation. Cardiovascular disease (CVD), malignancy and infections all limit patient and graft survival. Immunosuppressive medications alter innate and adaptive immunity and can result in immune dysfunction. Over suppression of the immune system can result in infections whereas under suppression can result in graft rejection. Exercise is a known therapeutic intervention with many physiological benefits. Its effects on immune function are not well characterised and may include both positive and negative influences depending on the type, intensity, and duration of the exercise bout. High intensity interval training (HIIT) has become more popular due to it resulting in improvements to tradional and inflammatory markers of cardiovascular (CV) risk in clinical and non-clinical populations. Though these improvements are similar to those seen with moderate intensity exercise, HIIT requires a shorter overall time commitment, whilst improvements can also be seen even with a reduced exercise volume. The purpose of this study was to explore the physiolocial and immunological impact of 8-weeks of HIIT and moderate intensity continuous training (MICT) in kidney transplan recipients (KTRs). In addition, the natural variations of immune and inflammatory cells in KTRs and non-CKD controls over a longitudinal period are explored. Newly developed multi-colour flow cytometry methods were devised to identify and characterise immune cell populations. Twenty-six KTRs were randomised into one of two HIIT protocols or MICT: HIIT A (n=8; 4-, 2-, and 1-min intervals; 80-90% VO2peak), HIIT B (n=8, 4x4 min intervals; 80-90% VO2peak), or MICT (n=8, ~40 min; 50-60% VO2peak) for 24 supervised sessions on a stationary bike (approx. 3x/week over 8 ± 2 weeks). Blood samples taken pre-training, mid training, post-training and 3 months later. Novel multi-colour flow cytometric panels were developed to characterise lymphoid and myeloid cell population from peripheral blood mononuclear cells. No changes were observed for circulating immune and inflammatory cells over the 8-week interventions. The feasibility study does not suggest that exercise programmes using HIIT and MICT protocols elicit adverse negative effects on immunity in KTRs. Therefore, such protocols may be immunologically safe for these patients. The inability of the participants to achieve the target exercise intensities may be due to physiological abnormalities in this population which warrants further investigation.

Perceived barriers and facilitators to exercise in kidney transplant recipients: A qualitative study.

BACKGROUND: Exercise has the potential to attenuate the high levels of cardiovascular morbidity and mortality present in kidney transplant recipients (KTRs). Despite this, activity levels in KTRs remain low. The aim of this qualitative study was to explore the barriers and facilitators of exercise in KTRs. METHODS: Thirteen KTRs (eight males; mean ± SD; age 53 ± 13 years; estimated glomerular filtration rate 53 ± 21 ml/min/1.73 m2 ) were recruited and completed semistructured one-to-one interviews at University Hospitals of Leicester NHS Trust. All KTRs were eligible if their kidney transplant was completed >12 weeks before interview and their consultant considered them to have no major contraindications to exercise. All interviews were audio recorded, transcribed verbatim and subject to framework analysis to identify and report themes. RESULTS: Themes were organized into personal, behavioural and environmental factors based on social cognitive theory. Facilitators of exercise were largely internal: enjoyment, exercise for general health and health of the transplanted kidney and desire to maintain normality. Social interaction, support and guidance of healthcare professionals and goal setting were perceived as motivational. Harming the kidney, a lack of guidance, self-motivation and accessibility were barriers to exercise. CONCLUSION: These results provide detailed insight into the development of interventions designed to increase physical activity in KTRs. They provide strong evidence that specific exercise guidelines are required for this population and that the healthcare system could have a key role in supporting KTRs to become more physically active. Interventions need to be multifaceted to appeal to the differing levels of support desired by KTRs. PATIENT OR PUBLIC CONTRIBUTION: KTRs were involved in the development of the interview topic guide to ensure all relevant topics were explored.

Intradialytic cycling does not exacerbate microparticles or circulating markers of systemic inflammation in haemodialysis patients.

PURPOSE: Patients receiving haemodialysis (HD) display elevated circulating microparticle (MP) concentration, tissue factor (TF) expression and markers of systemic inflammation, though regular intradialytic cycling (IDC) may have a therapeutic effect. This study investigated the impact of regular, moderate-intensity IDC on circulating MPs and inflammatory markers in unit-based HD patients. METHODS: Patients were cluster-randomised to intervention (n = 20, age: 51.4 ± 18.1 years, body mass: 77.6 ± 18.3 kg, mean ± SD) or no-exercise control (n = 20, 56.8 ± 14.0 years, 80.5 ± 26.5 kg). Intervention participants completed 30 min of moderate intensity (rating of perceived exertion [RPE] of 12-14) IDC, thrice weekly for 6 months. Pre-dialysis venous blood samples were obtained at 0, 3 and 6 months. Circulating MP phenotypes, cytokines, chemokine and MP TF expression were quantified using flow cytometry and cytometric bead array assays. RESULTS: Despite high exercise compliance (82%), no IDC-dependent effects were observed for any MP, cytokine or chemokine measure (p ≥ 0.051, ηρ2 ≤ 0.399) other than TNF-α (p = 0.001, ηρ2 = 0.186), though no significance was revealed upon post hoc analysis. CONCLUSION: Six months of regular, moderate-intensity IDC had no effect on MPs, cytokines or chemokines. This suggests that the exercise did not exacerbate thrombotic or inflammatory status, though further functional assays are required to confirm this. TRIAL REGISTRATION: ISRCTN1129707, prospectively registered on 05/03/2015.

The joint associations of physical activity and TV viewing time with COVID-19 mortality: An analysis of UK Biobank.

We used logistic regression to investigate the joint associations of physical activity level (high: ≥3000 MET-min/week, moderate: ≥600 MET-min/week, low: not meeting either criteria) and TV viewing time (low: ≤1 h/day, moderate: 2-3 h/day, high: ≥4 h/day) with COVID-19 mortality risk in UK Biobank. Additional models were performed with adjustment for body mass index (BMI) and waist circumference. Within the 373, 523 included participants, there were 940 COVID-19 deaths between 16 March 2020 and 12 November 2021. Compared to highly active individuals with a low TV viewing time, highly active individuals with a high TV viewing time were at significantly higher risk of COVID-19 mortality (odds ratio = 1.54, 95% confidence interval = 1.11-2.15). However, the greatest risk was observed for the combination of a low physical activity level and a high TV viewing time (2.29, 1.63-3.21). After adjusting for either BMI or waist circumference, only this latter combination remained at a significantly higher risk, although the effect estimate was attenuated by 43% and 48%, respectively. In sum, a high TV viewing time may be a risk factor for COVID-19 mortality even amongst highly active individuals. Higher adiposity appears to partly explain the elevated risk associated with a low physical activity level and a high TV viewing time.

A randomized controlled trial to investigate the effects of intra-dialytic cycling on left ventricular mass.

Cardiovascular disease is the leading cause of death for patients receiving hemodialysis. Since exercise mitigates many risk factors which drive cardiovascular disease for these patients, we assessed effects of a program of intra-dialytic cycling on left ventricular mass and other prognostically relevant measures of cardiovascular disease as evaluated by cardiac MRI (the CYCLE-HD trial). This was a prospective, open-label, single-blinded cluster-randomized controlled trial powered to detect a 15g difference in left ventricular mass measured between patients undergoing a six-month program of intra-dialytic cycling (exercise group) and patients continuing usual care (control group). Pre-specified secondary outcomes included measures of myocardial fibrosis, aortic stiffness, physical functioning, quality of life and ventricular arrhythmias. Outcomes were analyzed as intention-to-treat according to a pre-specified statistical analysis plan. Initially, 130 individuals were recruited and completed baseline assessments (65 each group). Ultimately, 101 patients completed the trial protocol (50 control group and 51 exercise group). The six-month program of intra-dialytic cycling resulted in a significant reduction in left ventricular mass between groups (-11.1g; 95% confidence interval -15.79, -6.43), which remained significant on sensitivity analysis (missing data imputed) (-9.92g; 14.68, -5.16). There were significant reductions in both native T1 mapping and aortic pulse wave velocity between groups favoring the intervention. There was no increase in either ventricular ectopic beats or complex ventricular arrhythmias as a result of exercise with no significant effect on physical function or quality of life. Thus, a six-month program of intradialytic cycling reduces left ventricular mass and is safe, deliverable and well tolerated.

Higher levels of physical activity are associated with reduced tethering and migration of pro-inflammatory monocytes in males with central obesity.

Despite evidence that monocyte migration is accentuated by central adiposity, the impact of physical activity (PA) and exercise, particularly in the post-prandial state, on limiting migration are not established. We hypothesised that PA and a single bout of walking exercise would be associated with reduced ex vivo monocyte tethering and migration in middleaged males with central obesity (CO). Objective levels of PA were measured for 7 days in lean males (LE, N=12, mean (SD) age 39 (10) years, waist circumference 81.0 (6.3) cm) and males with CO (N=12, mean (SD) age 40 (9) years, waist circumference 115.3 (13.9) cm), followed by donation of a fasted blood sample. On the same day, CO undertook a bout of walking exercise, before donation of a second fasted blood sample. An ex vivo assay, coupled to flow cytometry, determined tethering and migration of classical, intermediate, and non-classical monocytes. C-C and CXC chemokine receptor (CCR2, CCR5 and CX3CR1) expression were also determined on total and classical monocytes. Monocyte subsets (total, classical, intermediate and CCR2+ monocytes), metabolic (glucose and lipids) and inflammatory (C-reactive protein) markers were greater in CO vs. LE (lower highdensity lipoprotein); however, adjustments for PA mitigated group differences for glucose, lipids, and monocyte subsets. Ex vivo tethering and migration (absolute and relative) of most monocyte subsets was greater in CO vs LE. Relative monocyte tethering and migration was largely not influenced by PA; however, higher PA was associated with reduced absolute migration and tethering of CD16 expressing monocytes in CO. Prior walking had no impact on these variables. These results highlight that regular PA, not single exercise bouts may limit the migration of pro-inflammatory monocytes in CO. These changes may relate to physiological parameters in blood (i.e. number of cells and their adhesion), rather than differences in chemokine receptor expression.

Fasted plasma asprosin concentrations are associated with menstrual cycle phase, oral contraceptive use and training status in healthy women.

PURPOSE: Asprosin, an orexigenic hormone that stimulates hepatic glucose release, is elevated in insulin resistance and associated with obesity. Plasma asprosin concentrations may also be related to female sex hormone levels; higher levels are reported in women with polycystic ovary syndrome (PCOS) but this may be related to peripheral insulin resistance also associated with PCOS. Clarification of female-specific factors influence on the plasma asprosin response is crucial for studies investigating asprosin. Therefore, this study determined the association of menstrual phase, oral contraceptive (OC) use (as a pharmacological influence on sex hormone levels) and training status (as a physiological influence on sex hormone levels) on plasma asprosin levels in pre-menopausal women. METHODS: Fasting plasma asprosin, 17ß-estradiol (E2) and progesterone, were assessed in 32 healthy untrained and trained women with regular menstrual cycles (non-OC; n = 8 untrained, n = 6 trained) or using OC (n = 10 untrained, n = 8 trained) during early follicular, late follicular and mid-luteal menstrual phases (or the time-period equivalent for OC users). RESULTS: Asprosin was lower in OC (0.75 ± 0.38 ng mL-1) than non-OC users (1.00 ± 0.37 ng mL-1; p = 0.022). Across a cycle, asprosin was highest in the early follicular equivalent time-point in OC users (0.87 ± 0.37 ng mL-1) but highest in the mid-luteal phase in non-OC users (1.09 ± 0.40 ng mL-1). Asprosin concentrations varied more across a cycle in untrained than trained women, with higher concentrations in the early follicular phase compared to the late follicular and mid-luteal (training status-by-menstrual phase interaction p = 0.028). CONCLUSION: These findings highlight the importance of considering OC use, menstrual cycle phase and to a lesser extent training status when investigating circulating asprosin concentrations in females.

Influence of acute moderate- to high-intensity aerobic exercise on markers of immune function and microparticles in renal transplant recipients.

Renal transplant recipients (RTRs) and patients with nondialysis chronic kidney disease display elevated circulating microparticle (MP) counts, while RTRs display immunosuppression-induced infection susceptibility. The impact of aerobic exercise on circulating immune cells and MPs is unknown in RTRs. Fifteen RTRs [age: 52.8 ± 14.5 yr, estimated glomerular filtration rate (eGFR): 51.7 ± 19.8 mL·min-1·1.73 m-2 (mean ± SD)] and 16 patients with nondialysis chronic kidney disease (age: 54.8 ± 16.3 yr, eGFR: 61.9 ± 21.0 mL·min-1·1.73 m-2, acting as a uremic control group), and 16 healthy control participants (age: 52.2 ± 16.2 yr, eGFR: 85.6 ± 6.1 mL·min-1·1.73 m-2) completed 20 min of walking at 60-70% peak O2 consumption. Venous blood samples were taken preexercise, postexercise, and 1 h postexercise. Leukocytes and MPs were assessed using flow cytometry. Exercise increased classical (P = 0.001) and nonclassical (P = 0.002) monocyte subset proportions but decreased the intermediate subset (P < 0.001) in all groups. Exercise also decreased the percentage of platelet-derived MPs that expressed tissue factor in all groups (P = 0.01), although no other exercise-dependent effects were observed. The exercise-induced reduction in intermediate monocyte percentage suggests an anti-inflammatory effect, although this requires further investigation. The reduction in the percentage of tissue factor-positive platelet-derived MPs suggests reduced prothrombotic potential, although further functional assays are required. Exercise did not cause aberrant immune cell activation, suggesting its safety from an immunological standpoint (ISRCTN38935454).

Elevating body termperature to reduce low-grade inflammation: a welcome strategy for those unable to exercise?

Chronic low-grade inflammation is increasingly recognized in the aetiology of a range of chronic diseases, including type 2 diabetes mellitus and cardiovascular disease, and may therefore serve as a promising target in their prevention or treatment. An acute inflammatory response can be induced by exercise; this is characterised by the acute increase in proinflammatory markers that subsequently stimulate the production of anti-inflammatory proteins. This may help explain the reduction in basal concentrations of pro-inflammatory markers following chronic exercise training. For sedentary populations, such as people with a disability, wheelchair users, or the elderly, the prevalence of chronic low-grade inflammation- related disease is further increased above that of individuals with a greater capacity to be physically active. Performing regular exercise with its proposed anti-inflammatory potential may not be feasible for these individuals due to a low physical capacity or other barriers to exercise. Therefore, alternatives to exercise that induce a transient acute inflammatory response may benefit their health. Manipulating body temperature may be such an alternative. Indeed, exercising in the heat results in a larger acute increase in inflammatory markers such as interleukin-6 and heat shock protein 72 when compared with exercising in thermoneutral conditions. Moreover, similar to exercise, passive elevation of body temperature can induce acute increases and chronic reductions in inflammatory markers and positively affect markers of glycaemic control. Here we discuss the potential benefits and mechanisms of active (i.e., exercise) and passive heating methods (e.g., hot water immersion, sauna therapy) to reduce chronic low-grade inflammation and improve metabolic health, with a focus on people who are restricted from being physically active.

The Efficacy of Prebiotic, Probiotic, and Synbiotic Supplementation in Modulating Gut-Derived Circulatory Particles Associated With Cardiovascular Disease in Individuals Receiving Dialysis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This systematic review and meta-analyses provide an up-to-date synthesis on the effects of supplementation on circulating levels of toxic metabolites, markers of uremia and inflammation, blood lipids, and other clinical outcomes. METHODS: Seventeen databases were searched, supplemented with internet and hand searching. Randomized controlled trials of adult end-stage renal-disease individuals receiving either hemodialysis or peritoneal dialysis were eligible. Trials were restricted to those which had administered a prebiotic, probiotic, or synbiotic as an oral supplement. Primary outcomes were measures of circulating endotoxin, indoxyl-sulphate, and p-cresyl sulfate. RESULTS: Twenty-one trials were eligible (1152 randomized participants), of which 16 trials were considered to have a high risk of bias. The number of trials available for meta-analysis varied for each primary outcome. Synthesized data indicated that supplementation significantly reduced circulating levels of endotoxin (standardized mean difference, -0.61; 95% confidence interval, -1.03 to -0.20; P = .004; I2 = 0%), indoxyl-sulphate (-0.34; -0.64 to -0.04; P = .02; I2 = 0%), and p-cresyl sulfate (-0.34; -0.61 to -0.07; P = .01; I2 = 0%). For secondary outcomes, supplementation significantly reduced gastrointestinal symptoms (-0.54; -1.02 to -0.07; P = .02; I2 = 0%). CONCLUSIONS: Supplementation reduces toxic metabolites associated with cardiovascular disease and mortality in individuals receiving dialysis. However, the majority of trials included were low in quality.

Upper respiratory tract symptoms and salivary immunoglobulin A of elite female gymnasts: a full year longitudinal field study.

The aim of this study was to determine the frequency of upper respiratory tract symptoms (URS) in elite female gymnasts during a training season. In addition, we aimed to observe the extent to which salivary immunoglobulin A (sIgA) is associated with URS in these athletes, including potential effects of the season and timing of sample collection. Over one year, 18 elite female gymnasts completed URS and fatigue questionnaires weekly and provided 1 mL of saliva after a minimum 36 h of rest (morning or afternoon) to measure relative sIgA concentration (= mean absolute sIgA value of the week divided by the mean absolute sIgA value of the weeks without URS). Mean weekly URS and mean relative sIgA values per gymnast correlated negatively (r = -0.606, P = 0.022). Most URS were noted in the most fatigued gymnasts (7.4 ± 10.1 vs. 2.5 ± 5.6 (P < 0.001) for 'normal' and 2.1 ± 3.7 (P = 0.001) for 'better than normal' rested). In spring, relative sIgA was higher compared to autumn (112 ± 55 vs. 89 ± 41%, P < 0.001) and winter (92 ± 35%, P = 0.001), while during summer, relative sIgA appeared higher compared to autumn (110 ± 55 vs. 89 ± 41%, P = 0.016). The interaction effect with timing of sample collection showed higher relative sIgA values in morning samples in spring and summer compared to afternoon samples, with the inverse observed in autumn and winter (F = 3.565, P = 0.014). During a gymnastics season, lower relative sIgA values were linked to higher susceptibility to URS in elite gymnasts. However, relative sIgA values were influenced by season and timing of sample collection and thus should be considered when interpreting sIgA data.

Anti-inflammatory response to acute exercise is related with intensity and physical fitness.

PURPOSE: The relationship between inflammatory markers and energetic metabolism has been explored. However, the relationship between exercise intensity and fitness status is unclear, and it is necessary to understand this relationship to apply specific exercise guidance. The purpose of the study was to analyze metabolic and inflammatory responses imposed by acute exercise sessions performed at moderate, heavy, and severe intensities and their relationship with the physical fitness status. METHODS: Nineteen healthy male volunteers performed three acute exercise sessions until exhaustion or up to 60 minutes on a cycle ergometer at moderate (90% of first ventilatory threshold [VT1]), heavy (midpoint between VT1 and second ventilatory threshold [VT2]), and severe (midpoint between VT2 and maximal aerobic power) intensities. Blood lactate, glucose, NEFA, endotoxin, and cytokines were determined for each exercise session. Peripheral and lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10 was analyzed before, after, and 60 minutes after sessions. RESULTS: In peripheral blood, severe intensity increased lactate, endotoxin, and TNF-α immediately after exercise and glucose at 60 min after exercise. There was a trend for IL-10 increase at 60 minutes after exercise in peripheral blood. Immediately after exercise, LPS-stimulated TNF-α, IL-6, IL-6/IL-10 ratio, and lactate levels were higher in the severe intensity while nonester fatty acid levels decreased at this time. At 60 minute after exercise, higher concentrations of glucose and a trend for increased IL-10 were observed in severe intensity. A positive correlation was observed between maximal aerobic power and IL-10 ( r = 0.513; P = 0.042), and negative correlations between maximal aerobic power and endotoxin ( r = -0.531; P = 0.034) and lactate ( r = -0.538; P = 0.031) in heavy intensity. CONCLUSION: Our data show a novel finding that higher cytokine responses occur at higher intensities, mainly in severe intensity. However, the anti-inflammatory (IL-10) response was physical fitness-dependent.

The inflammatory response to a wheelchair half-marathon in people with a spinal cord injury - the role of autonomic function.

This study investigates the relationship between autonomic function and the inflammatory response to a wheelchair half-marathon in people with a spinal cord injury (SCI). Seventeen wheelchair athletes with a cervical SCI (CSCI, N = 7) and without CSCI (NON-CSCI, N = 10) participated in a wheelchair half-marathon. Blood was taken prior, post and 1 h post-race to determine the concentrations of adrenaline, noradrenaline, extracellular heat shock protein 72 (eHsp72) and interleukin-6 (IL-6). A sit-up tilt test was performed to assess autonomic function at rest. CSCI showed a lower supine ratio of the low and high frequency power of the variability in RR intervals (LF/HF RRI, p = 0.038), total and low frequency power of the systolic blood pressure variability (TP SBP, p < 0.001; LF SBP, p = 0.005) compared to NON-CSCI. Following the race, catecholamine concentrations increased only in NON-CSCI (p < 0.036). The increase in IL-6 post-race was larger in NON-CSCI (p = 0.040). Post-race catecholamine levels explained 60% of the variance in the IL-6 response (r = 0.77, p = 0.040), which was further increased when the resting autonomic function indices were added to the regression model (R2 > 81%, p < 0.012). In summary, the dampened acute inflammatory response to a wheelchair half-marathon in CSCI was strongly associated with the autonomic dysfunction present in this group.

Microparticles and Exercise in Clinical Populations.

Microparticles (MPs) are shed membrane vesicles released from a variety of cell types in response to cellular activation or apoptosis. They are elevated in a wide variety of disease states and have been previously measured to assess both disease activity and severity. However, recent research suggests that they also possess bioeffector functions, including but not limited to promoting coagulation and thrombosis, inducing endothelial dysfunction, increasing pro-inflammatory cytokine release and driving angiogenesis, thereby increasing cardiovascular risk. Current evidence suggests that exercise may reduce both the number and pathophysiological potential of circulating MPs, making them an attractive therapeutic target. However, the existing body of literature is largely comprised of in vitro or animal studies and thus drawing meaningful conclusions with regards to health and disease remains difficult. In this review, we highlight the role of microparticles in disease, comment on the use of exercise and dietary manipulation as a therapeutic strategy, and suggest future research directions that would serve to address some of the limitations present in the research to date.