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Improving understanding of exercise effects on in vitro T-lymphocyte function--the role of fluorescent cell division tracking.

It is now widely accepted that athletes undergoing intensive training and competition schedules are at increased risk of developing upper respiratory tract infections (URTI). T-lymphocytes are central to cell-mediated adaptive immune responses and have been the subject of many studies investigating the relationship between T-lymphocyte function, exercise and athlete health. A decrease in T-lymphocyte function following acute intensive exercise has commonly been described, making them a possible factor contributing to increased illness susceptibility in athlete populations. However, there is much controversy regarding the interpretation of traditional methodology (mitogen-induced proliferation assays) used to assess T-lymphocyte function during and after exercise. Carboxyfluorescein diacetate succinimidyl ester (CFSE) labelling of lymphocyte populations can provide unique insights into cell function at rest and with exercise due to its ability to quantify cell division on an individual cell basis. Using this technique, it has been found that the effect of exercise on T-lymphocyte function is mediated via an increase in lymphocyte apoptosis. This paper discusses some recent data in the context of improving understanding of the exercise effects on in vitro T-lymphocyte function.

Apoptosis↗

Knowledge of fresh medical graduates about immunization: impact of posting in community medicine.

Immunization being the most cost effective health intervention rightly forms an integral part of MCH health activities spectrum. Of late medical colleges in the country are directly involved from the planning to evaluation stages in the immunization programmes in their respective catchment areas. Immunization knowledge of 91 interns during their course of involvement in community work, was tested on the first day and last day of their three months posting in the Community Medicine Department. The study showed positive impact of training in the Department of Community Medicine on the performance levels of interns. This was found mainly attributable to effective interaction of interns with the community in the field and taking independent decisions as per the case requirements.

Community Medicine↗

Exercise training increases the näive to memory T cell ratio in old mice.

Aging is associated with changes in T cells including involution of the thymus gland and an imbalance in the proportion of näive (CD44lo) and memory (CD44hi) T cells in the periphery. Reversal of these changes may improve immunity in the aged. We sought to determine whether 4 months of moderately intense treadmill running (EXC; 5 days/week, 45 min/day, 13-22 m/min) in 2 month (Y) and 18 month (O) old male Balb/c mice would alter T lymphocyte profiles in the thymus and spleen when compared to sedentary controls (CON). Splenocytes and thymocytes were harvested 24-48 h after the last exercise session and analyzed using immunofluorescence and flow cytometry. While there were significant age-related changes (lower cell number, altered subsets) in the thymuses of O when compared to Y mice, exercise training failed to affect any of these measures in mice of either age. Aged mice exhibited a significantly (p < .05) higher percentage of splenic memory cells and a lower percentage of näive cells in both the CD4 and CD8 T cell subsets. Interestingly, exercise training significantly (p < .05) increased the percentage of näive and decreased the percentage of memory cells in both the CD4+ (69.6+/-1.7% näive and 30.4+/-1.7% memory for OCON vs. 75.0+/-1.5% näive and 25.0+/-1.5% memory in OEXC) and CD8+ (60.0+/-2.6% näive and 40.0+/-2.6% memory in OCON vs. 76.7+/-2.7% näive and 23.3+/-2.7% memory in OEXC) T cells subsets in O, but not Y, mice. This effect was due to a decrease in the absolute number of memory cells and not an increase in the absolute number of näive cells. We conclude that 4 months of EXC has little restorative effect on the thymus in aged mice, but can restore the percentages of näive and memory cells in the spleen towards that of young mice, perhaps due to removal of memory cells.

Aging↗

Genome-wide Association Studies of the Pathogenic Sphingosine-1-Phosphate Gene in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that can lead to malignancies over time. Sphingosine-1-phosphate (S1P) receptor signaling affects lymphocyte trafficking and vascular integrity, influencing intestinal inflammation. This study aimed to identify S1P-related key genes in UC. METHODS: Differentially expressed genes (DEGs) between the UC and control groups were analyzed in the GSE87473 (training) dataset. Genes overlapping between the DEGs and S1P-related genes were considered candidate genes. These genes were incorporated into machine learning algorithms and subjected to expression analysis to identify key genes. Gene functions were determined through a gene&#x2013;gene interaction network, enrichment analysis, and immune cell infiltration analysis. In addition, transcription factor&#x2013;mRNA and mRNA&#x2013;miRNA&#x2013;lncRNA networks were constructed. Finally, reverse transcription&#x2013;quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of key candidate genes in UC and control tissues. RESULTS: This study identified two key genes (SPHK2 and SPNS2) associated with UC. Notably, SPHK2 expression was lower and SPNS2 expression was higher in the UC group in both training and validation datasets and in clinical UC tissues (RT-qPCR). The area under the curve values of SPHK2 and SPNS2 exceeded 0.7 in both datasets, indicating that the genes had good diagnostic efficacy for UC. Consistently, the nomogram showed that the two genes had promising diagnostic value in UC. SPHK2 and SPNS2 were found to be localized to the plasma membrane. The correlations of the two genes with different immune cells showed significantly opposite trends. In particular, SPHK2 had the strongest positive correlation with M2 macrophages (r = 0.6) and the strongest negative correlation with neutrophils. Moreover, mRNA&#x2013;miRNA&#x2013;lncRNA and transcription factor&#x2013; mRNA networks of the key genes were constructed. CONCLUSION: This study suggests that SPHK2 and SPNS2 are key genes associated with UC, highlighting their potential as effective diagnostic biomarkers.

Humans↗

Applying workflow analysis tools to assess immunization delivery in outpatient primary care settings.

BACKGROUND: As health care organizations face increasing pressure to institute quality assurance activities, the already-underfunded community clinics that treat the poor and underserved are challenged to perform these activities within tight constraints of human and financial resources. With pediatric immunizations as a marker, a workflow observation tool was used to identify causal processes affecting immunization delivery. METHODS: Ten clinics and five private practices, located in areas designated as health professional shortage areas, participated in the study, gaining access to a tool that would have been unaffordable to them from the private sector. Trained observers followed families through the clinic, using a 127-item workflow observation form--the Observational Checklist of Patient Encounters (OCPE)--assessing discrete activities that families encountered during the checkin/pre-exam, exam, discharge, and billing processes. A convenience sampling of the targeted population--children younger than three years of age--included observations of scheduled acute, scheduled well-child, follow-up, and walk-in visits. In the feedback session, a summary of each clinic's immunization delivery patterns was presented, with an emphasis on the individual health center's operational issues. RESULTS: The workflow observation tool was used to identify operational errors affecting both clinical and fiscal processes in each of the clinics that had not been previously apparent to either clinic management or the quality improvement (QI) teams. DISCUSSION: Feedback addressed and encouraged process-oriented improvements in response to the workflow observations, which were incorporated into the clinics' QI procedures. Twelve of the 15 clinics have formed process action teams to address QI issues on an ongoing basis.

Age Factors↗

Influence of acute vitamin C and/or carbohydrate ingestion on hormonal, cytokine, and immune responses to prolonged exercise.

The aim of the present study was to investigate the effect of vitamin C with or without carbohydrate consumed acutely in beverages before and during prolonged cycling on immunoendocrine responses. In a single blind, randomized manner six healthy, moderately trained males exercised for 2.5 h at 60% VO(2max)and consumed either placebo (PLA), carbohydrate (CHO, 6% w/v), vitamin C (VC, 0.15% w/v) or CHO+VC beverages before and during the bouts; trials were separated by 1 wk. CHO and CHO+VC significantly blunted the post-exercise increase in plasma concentrations of cortisol, ACTH, total leukocyte, and neutrophil counts and limited the decrease in plasma glucose concentration and bacteria-stimulated neutrophil degranulation. VC increased plasma antioxidant capacity (PAC) during exercise (P < 0.05) but had no effect on any of the immunoendocrine responses (P > 0.05). CHO+VC increased PAC compared to CHO but had no greater effects,p above those observed with CHO alone, on any of the immunoendocrine responses. In conclusion, acute supplementation with a high dose of VC has little or no effect on the hormonal, interleukin-6, or immune response to prolonged exercise and combined ingestion of VC with CHO provides no additional effects compared with CHO alone.

Adrenocorticotropic Hormone↗

Utilization of maternal services in west Bengal.

A study was conducted in selected blocks of West Bengal to assess the utilization of available maternal health services specially immunization, antenatal care and other services. Coverage with two doses of tetanus toxoid levels varied between 58.6 to 86.7% but it fell far short of Universal Immunization Programme target of 100%. Drop out rates were slightly higher in the rural areas. It was observed that in 5 out of 7 blocks more than 55% of the deliveries were conducted either at hospital or Primary Health Centre by health personnel. However, untrained dais predominated over the trained dais in conducting deliveries in most of the areas. This indicates the poor availability or utilization of the latter.

Female↗

Elite athlete immunology: importance of nutrition.

Immunosuppression in athletes involved in heavy training is undoubtedly multifactorial in origin. Training and competitive surroundings may increase the athlete's exposure to pathogens and provide optimal conditions for pathogen transmission. Heavy prolonged exertion is associated with numerous hormonal and biochemical changes, many of which potentially have detrimental effects on immune function. Furthermore, improper nutrition can compound the negative influence of heavy exertion on immunocompetence. An athlete exercising in a carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. The poor nutritional status of some athletes may predispose them to immunosuppression. For example, dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. An adequate intake of iron, zinc and B vitamins is particularly important but the dangers of over-supplementation should also be emphasized; many micronutrients given in quantities beyond a certain threshold will in fact reduce immune responses and may have other toxic effects that are detrimental to health. Although it is impossible to counter the effects of all of the factors that contribute to exercise-induced immunosuppression, it has been shown to be possible to minimize the effects of many factors. Athletes can help themselves by eating a well-balanced diet that includes adequate protein and carbohydrate, sufficient to meet their energy requirements. This will ensure a more than adequate intake of trace elements without the need for special supplements. Consuming carbohydrate (but not glutamine) during exercise attenuates rises in stress hormones such as cortisol and appears to limit the degree of exercise-induced immunosuppression. By adopting sound nutritional practice, reducing other life stresses, maintaining good hygiene, obtaining adequate rest and spacing prolonged training sessions and competition as far apart as possible, athletes can reduce their risk of infection.

Dietary Carbohydrates↗

Metabolic and mitogenic signal transduction in human skeletal muscle after intense cycling exercise.

We determined whether mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase (AMPK) signalling cascades are activated in response to intense exercise in skeletal muscle from six highly trained cyclists (peak O(2) uptake (.V(O2,peak)) 5.14 +/- 0.1 l min(-1)) and four control subjects (Vdot;(O(2))(,peak) 3.8 +/- 0.1 l min(-1)) matched for age and body mass. Trained subjects completed eight 5 min bouts of cycling at approximately 85% of .V(O2,peak) with 60 s recovery between work bouts. Control subjects performed four 5 min work bouts commencing at the same relative, but a lower absolute intensity, with a comparable rest interval. Vastus lateralis muscle biopsies were taken at rest and immediately after exercise. Extracellular regulated kinase (ERK1/2), p38 MAPK, histone H3, AMPK and acetyl CoA-carboxylase (ACC) phosphorylation was determined by immunoblot analysis using phosphospecific antibodies. Activity of mitogen and stress-activated kinase 1 (MSK1; a substrate of ERK1/2 and p38 MAPK) and alpha(1) and alpha(2) subunits of AMPK were determined by immune complex assay. ERK1/2 and p38 MAPK phosphorylation and MSK1 activity increased (P < 0.05) after exercise 2.6-, 2.1- and 2.0-fold, respectively, in control subjects and 1.5-, 1.6- and 1.4-fold, respectively, in trained subjects. Phosphorylation of histone H3, a substrate of MSK1, increased (P < 0.05) approximately 1.8-fold in both control and trained subject. AMPKalpha(2) activity increased (P < 0.05) after exercise 4.2- and 2.3-fold in control and trained subjects, respectively, whereas AMPKalpha(1) activity was not altered. Exercise increased ACC phosphorylation (P < 0.05) 1.9- and 2.8-fold in control and trained subjects. In conclusion, intense cycling exercise in subjects with a prolonged history of endurance training increases MAPK signalling to the downstream targets MSK1 and histone H3 and isoform-specific AMPK signalling to ACC. Importantly, exercise-induced signalling responses were greater in untrained men, even at the same relative exercise intensity, suggesting muscle from previously well-trained individuals requires a greater stimulus to activate signal transduction via these pathways.

AMP-Activated Protein Kinases↗

[Vaccination status of medical students in munich - results of a questionnaire survey].

BACKGROUND: Vaccinations, e. g., against hepatitis B, are recommended for health care workers in order to minimize the risk of occupational infections. While medical students come into contact with patients early in their medical education, sufficient vaccination is not routinely checked during their training. Hence, we wanted to assess the prevalence of medical students (fourth year) not sufficiently vaccinated against occupationally relevant infectious diseases (hepatitis A and B, measles, mumps, German measles, poliomyelitis) at the two medical schools in Munich. METHODS: One hundred and forty nine students of the medical school at the Ludwig-Maximilians-University and 89 students of the medical school at the Technical University completed a standardized questionnaire on demographic data, vaccination status and personal attitude towards vaccinations. RESULTS: Nine percent of the students at the Ludwig-Maximilans-University and one percent of the medical students at the Technical University reported not to have been vaccinated against hepatitis B. The relative frequency of students not vaccinated against hepatitis A was higher and did not differ between the medical schools (LMU: 35.9 %, TU: 40.5 %; 95 % Confidence Interval for the difference: -17.7-+ 8.5 %). The prevalence of vaccination especially against German measles among women was unsatisfactory. Individual vaccination status of the students seemed to be related to their personal attitude towards vaccinations. CONCLUSION: In order to increase the prevalence of hepatitis B vaccination among medical students they should be informed more intensively about the free of charge vaccination early during their education, e. g., before the beginning of their medical training.

Adult↗

S100 brain protein: correlation with behavior.

The brain-specific acidic protein, S100, in the pyramidal nerve cells of the hippocampus was investigated as a possible correlate to learning during transfer of handedness in rats. The amount of S100 increased during training. Intraventricular injection of antiserum against the S100 protein during the course of training prevented the rats from further increases in learned behavior but did not affect motor function in the animals. Antibodies against the S100 protein could be localized after injection by immunofluorescence, in hippocampal structures, penetrating presumably through slight ependymal lesions caused by the injection. By contrast, control animals subjected to the same training and injected with S100 antiserum that had been absorbed with S100 protein or with other antisera against gamma-globulins showed no decrease in their ability to learn. The conclusion is that the brain-specific protein, S100, is linked to the learning process, at least within the training used.

Animals↗

Immunisation for all?

Immunisation programmes can be successful if there is continuous effort among those concerned, who have confidence in their knowledge, and a high level of commitment to immunisation. Training is required for all. Feedback of results is essential.

Counseling↗

A description of travel medicine in general practice: a postal questionnaire survey.

BACKGROUND: Travel-related diseases are important aspects of public health. The number of UK residents traveling abroad is increasing at a rate of 16% a year, thereby increasing exposure to travel-related morbidity. Provision of comprehensive pretravel health advice is essential to reduce this trend. In the UK, pretravel health advice is predominantly provided through general practices. METHODS: A postal questionnaire was sent to all 91 general practices in South Cheshire Health Authority. The questionnaires were to be completed by the lead advisor in travel medicine for each practice. Questions were asked on service provision, training and reference resources used, subjects advised on, and health promotion material used. Nonresponders were contacted and sent a further questionnaire. RESULTS: A response rate of 86% (78/91) was achieved. Of the lead advisors, 97% were nurses and 3% general practitioners. Thirty-eight sources of advice were quoted, the commonest of which comprised wall immunization charts (72%). Duration of consultation ranged from less than 5 min to over 30 min, with a median and mode of 11 to 15 min. Most respondents reported advising on most travel-associated risks, 40% of practices lacked a protocol, and 83% of providers had attended a training course on travel medicine for 2 days or less. CONCLUSIONS: This survey identified inadequacies of training and use of multiple sources of reference which may lead to inconsistencies in advice. Most practitioners could not define their workload in travel medicine. For effective protection of travelers, a careful risk assessment, clear risk communication and health education with detailed health promotion are necessary, but these are not likely to be provided within an average consultation time of 11 to 15 min. There is no evidence of consistent governance, planned training and monitoring of service quality of travel medicine practice. This may be due to lack of a national policy on best practice and guidance in this subject. National protocols with validated information resources, set standards of training, along with adequate consultation time for educating, advising, and prescribing, will lead to improved health of the traveling public.

Communicable Disease Control↗

[Mass chemoprophylaxis of malaria, its objectives, its limits, its difficulties].

In intertropical Africa, insecticide spreadings cannot succeed by themselves in controlling malarial endemia. They cannot provide any eradication, even if they are combined with chemoprophylaxis. On the other hand, mass chemoprophylaxis should provide a control of lethality and morbidity due to malaria. The authors define the mass prophylaxis concept, lay its basic principles and specifically the criteria used to select the available anti-malarial drugs. Then, they stress on the major set-backs such as P. falciparum resistance to amino-4-quinoleine, and drop of immunity in individuals receiving no chemoprophylaxis. Finally, they review the necessary conditions for the achievement of a mass chemoprophylaxis at a wide country level, namely: a determined policy with long term budget allowances, setting up of a specific organization and personnel training, community education at all levels, preliminary epidemiological surveys and strategical schemes suited to the various epidemiological patterns.

Adolescent↗

Physical exercise as a human model of limited inflammatory response.

An inflammatory response represents a fundamental series of humoral and cellular reaction cascades in response to infection, tissue injury, and related insults. An excessive response is commonly seen under the pathological conditions of trauma, sepsis, and burns. It is becoming increasingly evident that most, if not all, of the distinguishing features of a classical inflammatory response are detectable in an exercising individual, namely mobilization and activation of granulocytes, lymphocytes, and monocytes; release of inflammatory factors and soluble mediators; involvement of active phase reactants; and activation of the complement and other reactive humoral cascade systems. While the manifestation of many exercise-induced immune and related changes has been reported and confirmed repeatedly, the underlying mechanisms triggering and modulating the elicited immune responses are, at best, poorly understood. Unlike the exaggerated and sometimes uncontrollable inflammatory response in septic and trauma patients resulting in morbidity and mortality, strenuous and severe exercise normally elicits an inflammatory response of a subclinical nature to facilitate the repairing process for site-specific tissue damage. Regardless of the inciting event, for example trauma, infection, or exercise, and given an appropriate triggering signal, a remarkably similar sequence of inflammatory reactions can be reproduced in the affected host. Therefore, physical exercise and training represent an acceptable and good model for the study of limited inflammatory responses in humans.

Cytokines↗

Video-assisted thoracoscopic pulmonary surgery--current status and potential evolution.

The current status of video-assisted thoracoscopic surgery (VATS) of the lung has been reviewed. The published data support the view that VATS pulmonary surgery is feasible and safe. It is associated with decreased perioperative pain and opiate requirement, better postoperative pulmonary function, and probable overall neutral cost impact. A VATS approach is functionally superior to open thoracotomy for wedge resection, pneumothorax surgery and bullous lung disease and may allow surgical intervention in patients with pulmonary function which is in adequate for open resection. Major VATS pulmonary resection with lobectomy and pneumonectomy can be performed for early malignant disease without compromising established surgical principles. Specific training is needed in VATS surgery and background skills in general thoracic surgery are necessary to underwrite major interventions. Decreased cytokine activation and enhanced post surgical immune function may prove to be long-term benefits of VATS surgery.

Endoscopy↗

Strength, workload, anaerobic intensity and the immune response to resistance exercise in women.

AIM: The mechanism linking exercise intensity to the magnitude of the immune response is not completely understood. The purpose of this investigation was to determine whether the immune response to resistance exercise was associated with (1) changes in workload or (2) anaerobic exercise intensity. METHODS: Previously untrained women underwent 6 months of resistance training for lower and upper body (TOTAL, n = 34) or for upper body alone (UPPER, n = 30). Lymphocyte subsets [T (CD3+), CD4+, CD8+, NK and B], functional markers (CD45RA+ and CD45RO+), and mitogen (phytohemagglutinin-M, concanavalin A and pokeweed mitogen) and superantigen (staphylococcus a. cowans)-stimulated proliferation were measured from blood samples collected pre- and post-exercise for a squat resistance exercise consisting of six sets of 10 repetitions at 75% of one repetition maximum. This protocol was performed before (T0) and after 3 (T3) and 6 months (T6) of training. RESULTS: Lymphocyte recruitment to the circulation and proliferation following resistance exercise did not differ between training groups at any time, although the TOTAL group performed at a higher workload as training progressed. With respect to anaerobic intensity, exercise-induced increases in NK, CD4+, CD8+ and B lymphocyte concentrations were 42 (P = 0.07), 76 (P < 0.05), 72 (P < 0.05) and 242% (P < 0.01) greater in women in the highest compared with the lowest post-exercise lactate quartiles. Lymphocyte proliferation did not differ between lactate quartiles. CONCLUSIONS: Anaerobic intensity, rather than increased strength and workload, is associated with the number of lymphocytes recruited to the circulation, but not T and B cell proliferation responses.

Adolescent↗