The role of global and regional DNA methylation and histone modifications in glycemic traits and type 2 diabetes: A systematic review.

BACKGROUND: New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition and environmental influences. AIM: To systematically review studies investigating the association between epigenetic marks (DNA methylation and histone modifications) with T2D and glycemic traits (glucose and insulin levels, insulin resistance measured by HOMA-IR). METHOD AND RESULTS: Six bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, PubMed, Cochrane Central and Google Scholar) were screened until 28th August 2015. We included randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined the association between epigenetic marks (global, candidate or genome-wide methylation of DNA and histone modifications) with T2D, glucose and insulin levels and insulin metabolism. Of the initially identified 3879 references, 53 articles, based on 47 unique studies met our inclusion criteria. Overall, data were available on 10,823 participants, with a total of 3358 T2D cases. There was no consistent evidence for an association between global DNA-methylation with T2D, glucose, insulin and insulin resistance. The studies reported epigenetic regulation of several candidate genes for diabetes susceptibility in blood cells, muscle, adipose tissue and placenta to be related with T2D without any general overlap between them. Histone modifications in relation to T2D were reported only in 3 observational studies. CONCLUSIONS AND RELEVANCE: Current evidence supports an association between epigenetic marks and T2D. However, overall evidence is limited, highlighting the need for further larger-scale and prospective investigations to establish whether epigenetic marks may influence the risk of developing T2D.

Chemotherapy at First Diagnosis of Advanced Prostate Cancer - Revolution or Evolution? Findings from a British Uro-oncology Group UK Survey to Evaluate Oncologists' Views on First-line Docetaxel in Combination with Androgen Deprivation Therapy in Castrate-sensitive Metastatic and High-risk/Locally Advanced Prostate Cancer.

AIMS: There have been three randomised trials investigating docetaxel in combination with androgen deprivation therapy as first-line therapy for hormone-sensitive metastatic and locally advanced/high-risk prostate cancer. The largest of these studies, UK STAMPEDE trial, recently presented in June 2015. The aim of this survey was to evaluate if oncologists' practice has changed as a result of these studies, or if their practice is likely to change in different clinical settings in the future. MATERIALS AND METHODS: The British Uro-oncology Group issued a semi-structured online questionnaire to its membership of 160 specialist urological oncologists practising in the UK. Links to the abstracts of GETUG-AFU-15, E3805 CHAARTED and STAMPEDE were attached with the survey for respondents to review before completing the survey. RESULTS: In total, 111 participants completed the survey; 87% stated that STAMPEDE will influence their clinical practice in the future. Almost all (96%) would offer docetaxel with androgen deprivation therapy to men presenting with high volume metastatic prostate cancer. Fewer oncologists would offer this treatment to men with low volume metastatic prostate cancer, locally advanced or relapsed disease. Various patient- and disease-related factors were considered in decision making, as well as resource implications. CONCLUSIONS: This survey reports oncologists' attitudes towards a major change in practice in the standard of care for men with newly diagnosed advanced prostate cancer in the UK. The survey highlighted the complexities surrounding the clinical implementation of the data from these studies, including changes in referral pathways, with the early involvement of oncologists in such patients' care, increases in workloads for oncologists and chemotherapy units and the need for national approval for re-imbursement of these treatments.

Nasty or Nice? Findings from a UK Survey to evaluate the impact of the National Institute for Health and Clinical Excellence (NICE) clinical guidelines on the management of prostate cancer.

AIMS: Although the National Institute for Health and Clinical Excellence clinical guideline 58 (CG58) for prostate cancer management was expected to have a positive effect, several recommendations raised concern among UK physicians. We conducted a survey of UK oncologists in 2008 and a second, similar survey in 2010 to assess views on these recommendations and to evaluate the change in opinion over time. MATERIALS AND METHODS: Two semi-structured questionnaires were issued by the British Uro-oncology Group to society members in September 2008 and October 2010. RESULTS: In 2008, 61 UK oncologists completed the survey; 60% agreed that CG58 would make a positive contribution towards improving patient care. There was strong opposition towards active surveillance as the first-line treatment for men with low-risk localised prostate cancer (49% disagreement); implementing 5 yearly flexible sigmoidoscopy post-prostate radiotherapy (51% disagreement); offering follow-up outside of the hospital (e.g. by general practitioners in primary care) for men with a stable prostate-specific antigen for ≥2 years (44% disagreement); and recommendations against docetaxel retreatment (47% disagreement) or bisphosphonate use (58% disagreement). In 2010, 77 UK oncologists completed the survey. The results were largely consistent with 2008, although several recommendations, particularly for localised disease, seem to have promoted a change in clinical practice, suggesting that they are facilitating a standardised approach. Compared with 2008, the 2010 results indicate a shift in favour of active surveillance (80% agreement) and primary care follow-up (59% agreement), but increasing opposition for docetaxel retreatment (57% disagreement). Opinions remained divided for flexible sigmoidoscopy and bisphosphonates. CONCLUSIONS: Despite initial concerns, the CG58 seems to have had a positive impact on prostate cancer management in the UK, with adherence likely facilitating a standardised approach. However, with new data emerging, these findings underscore the need to regularly update guidelines. A revision of the CG58 is anticipated by 2014.

Efficacy of partially hydrolyzed guar gum-added oral rehydration solution in the treatment of severe cholera in adults.

BACKGROUND: Partially hydrolyzed guar gum (PHGG) is a water-soluble fiber if added to oral rehydration solution (ORS) and undergoes fermentation in the colon liberating short chain fatty acids (SCFAs). SCFAs potentiate the effect of ORS, reducing the severity of diarrhea. AIM: To examine the effect of PHGG-added ORS in reducing the stool output and duration of diarrhea in adult cholera. METHODS: 195 male patients were studied in a randomized controlled trial: (a) 65 received ORS + 25 g PHGG; (b) 65 received ORS + 50 g PHGG, and (c) 65 received ORS alone (control). Major outcomes were stool weight and duration of diarrhea. RESULTS: No significant differences were found in mean +/- SD stool weight (g/kg b.w.) during the first and second 24 h. In the subgroup analysis (excluding very high purging patients, stool weight in the first 24 h was >10 kg), the stool weight (g/kg b.w.) was significantly reduced in the first 24 h in both groups receiving PHGG (PHGG 25 g, 136 +/- 68 vs. PHGG 50 g, 144 +/- 49 vs. control, 176 +/- 43, p = 0.01). CONCLUSION: PHGG-added ORS might have a beneficial effect in moderately purging adult cholera. However, further studies are warranted to confirm the preliminary findings.

Low back pain among nurses: a follow-up beginning at entry to the nursing school.

STUDY DESIGN: A prospective cohort. OBJECTIVES: To investigate the prevalence of back pain from entering the nursing school through 5 years in nursing and the determinants and modifiers of back pain and disability. SUMMARY OF BACKGROUND DATA: Physical loading, psychologic characteristics, and several other factors have been associated with back pain at work in earlier studies. Because of the lack of the prework entry morbidity data, the nature of the associations between these exposures and the symptoms is unclear. That previous back pain is a predictor of later pain underlines the importance to have pre-employment data in investigations of the role of exposures at work. METHODS: Female nursing students (n = 174) were followed for 7.5 years. Data on constitutional and behavioral factors, occupational exposures, and back-related symptoms and disability were collected. Back pain was grouped into "sciatic," "sudden," or "other" and related disability. RESULTS: The lifetime cumulative prevalence of back pain increased from 31% at entry to nursing school to 72% at the end of the school and further to 82% after 5 years as a nurse. The 1-year prevalence of any back pain was 54% for the first year in nursing school, 57% for the first year as a nurse, and 64% for the fifth year as a nurse. In multivariate analyses, other back pain and related disability as a nurse were associated with back pain history at the entry to nursing school (odds ratio, 7.1; 95% confidence interval, 1.5-34; and 3.6; 1.2-11, respectively), and working in twisted/bent positions (odds ratio, 6.2; 95% confidence interval, 1.7-23; and 7.5; 2.9-20, respectively). Sudden back pain was not associated with any of the studied risk factors. Sciatic back pain was associated only with working positions (odds ratio, 6.9; 95% confidence interval, 2.1-23). CONCLUSIONS: Lifetime prevalence of back pain increased sharply during nursing school but slowly after that. Back pain at entering the nursing school was a predictor for back-related pain and disability. Self- reported occupational physical work load was associated with back pain and related disability. The nature of the association is unclear, but it is likely that back pain is exacerbated during nursing.

The physiology and biomechanics of competitive swimming.

Fast swimming, either in the pool, in open water swimming, or in water polo and synchronized swimming, requires maximizing the efficiencies with which the human body can move through a liquid medium. A multitude of factors can affect the ability to swim fast as well as the final outcome. Physiology and biomechanics are the present tools used by sports scientists to determine which factors are important to fast swimming and, subsequently, to determine how the swimmer may maximize these factors to improve performance.

Energy expenditure of swimmers during high volume training.

The purpose of this study was to examine the total energy expenditure (TEE) of swimmers during high volume training (17.5 +/- 1.0 km.d-1) using the doubly labeled water method. Five female swimmers (age, 19 +/- 1 yr; height, 178.3 +/- 2.2 cm; weight 65.4 +/- 1.6 kg) were administered a dose of 2H2(18)O and monitored for 5 days. Training consisted of two sessions per day, lasting a total of 5-6 h. Energy intake (EI) was calculated from dietary records. Resting energy expenditure (REE) was measured on a non-training day and averaged 7.7 +/- 0.5 MJ.d-1 (1840 +/- 130 kcal.d-1). There were no changes in body weight (day 1, 65.4 +/- 1.6; day 5, 65.2 +/ 1.5 kg) over the measurement period. TEE of the swimmers during the training period averaged 23.4 +/- 2.1 MJ.d-1 (5593 +/- 495 kcal.d-1). EI averaged 13.1 +/- 1.0 MJ.d-1 (3136 +/- 227 kcal.d-1), implying a negative energy balance of 43 +/- 2%. TEE expressed as a multiple of REE was 3.0 +/- 0.2. The results of this investigation describe the total energy demands of high volume swimming training, which may be used to address the dietary concerns of the competitive swimming athlete.

Rating of acceptable load in manual sorting of postal parcels.

The psychophysical test, the rating of acceptable load (RAL) were used to assess acceptable weights for dynamic lifting in postal workers engaged in sorting parcels. The standard test (RALSt) and a work-simulating test (RALW) were administered to 103 volunteers: all experienced male sorters. In the RALSt, subjects selected the weight which would be acceptable for lifting in a box with handles from table to floor and back to the table once every 5 min for the working day. for the RALW, the box was without handles and the weight was chosen to be acceptable for transfer 4-6 times/min from a table to the parcel container and back to the table. Both tests were made during normal working hours at postal sorting centres. The overall means for RALSt and RALW were 16.4 kg and 9.4 kg respectively (p < 0.001): both being substantially higher than the average parcel weight of 4 kg. The RALSt and RALW tests proved to be repetitive and sensitive for differentiating the effects of load and task variable in actual manual material handling. Thus they appear to be applicable to the evaluation of manual materials handling problems.

Physiological responses to swimming while wearing a wet suit.

The purpose of this study was to examine the influence of three different wet suits on the oxygen uptake (VO(2)), minute ventilation (VE). and heart rate responses to front crawl swimming. Five male subjects swam at four velocities (0.90, 1.05, 1.18 +/- 0.01, 1.31 +/- 0.02 m.sec(-1)) in each of four swimming suit conditions in a swimming flume. Conditions were completed in random order using a conventional swimming suit (SS), a wet suit that covered the full body (FULL), a wet suit that left the arms exposed (LONG), and a wet suit that left the arms and lower legs exposed (SHORT). Water temperature was 26.5 +/- 1.0 degrees C for all trials. VO(2) and V(E) were decreased (p < 0.05) while swimming in the three wet suits as compared to the SS at all four velocities. VO(2) and V(E) were also lower (p < 0.05) in the FULL as compared to the SHORT at all four velocities; however, there were no differences between the SHORT and LONG or LONG and FULL at any of the velocities. Decreases in VO(2) from SS averaged 16.2 +/- 1.9 (SHORT), 22.8 +/- 2.4 (LONG), and 33.6 +/- 2.9% (FULL) over all four velocities. Similarly, reductions in V(E) from SS averaged 14.6+/- 1.5, 19.6 +/- 1.6, 24.2 +/- 1.5%, in the SHORT, LONG, and FULL, respectively. Heart rate and rating of perceived exertion were higher (p < 0.05) in the SS as compared to the three wet suits at 1.31 m.sec(-1) only. In conclusion, oxygen uptake and minute ventilation during swimming at a given velocity were decreased when wearing a wet suit as compared to a conventional swimming suit. Further, these decreases were related to the amount of wet suit covering the body.

Isotopic determination of glycolytic flux during intense exercise in humans.

We used a new stable isotope tracer approach incorporating muscle intracellular lactate enrichment to determine the flux of glucose/glucosyl toward lactate [i.e., nonoxidized pyruvate (Pyr) production (Pyrno)] in moderately trained cyclists exercising at approximately 80% (259 +/- 16 W; n = 6) and approximately 100% (341 +/- 9 W; n = 8) maximal O2 uptake (VO2max). Primed constant infusions of [6,6-2H2]glucose and [13C]lactate or [13C]Pyr tracers were given, and rapid achievement of plateau was obtained during exercise by increasing the infusion rates at exercise onset to correspond with expected increases in production. The accumulated O2 deficit was simultaneously determined over the 1st 3 min of exercise as an indirect means of quantifying glycolytic flux for comparison with our tracer-determined values and was significantly greater at the higher intensity (38 +/- 3 vs. 30 +/- 3 ml O2.kg-1.3 min-1; P < 0.02). Pyrno was also significantly higher (6.38 +/- 0.91 vs. 4.38 +/- 0.65 mmol.kg-1.min-1 over 3 min at 100 and 80% VO2max, respectively). The blood lactate rate of appearance at approximately 100% VO2max (828 +/- 69 mumol.kg-1.min-1) represented a higher percentage of Pyr rate of appearance (RaPyr; 31 +/- 3%) than that at approximately 80% VO2max (416 +/- 36 mumol.kg-1.min-1; 22 +/- 2%; P < 0.02). Although only approximately 27 +/- 2% of RaPyr was oxidized, this provided 78 +/- 2% of the total energy demand during the 1st 3 min of exercise at either intensity. Our new method provided values for Pyrno that were in the expected range and were highly correlated with respective accumulated O2 deficit values (r = 0.87, P < 0.0001). In conclusion, our new tracer method appears to be valid for the measurement of RaPyr and Pyrno during high-intensity exercise lasting even < 10 min.

The prediction of chronicity in patients with an acute attack of low back pain in a general practice setting.

STUDY DESIGN: Three hundred patients, attending their general practitioners with attacks of acute low back pain, formed the subject population for a study of fear avoidance and other variables in the prediction of chronicity. Follow-up was at 2 and 12 months. OBJECTIVE: The hypothesis to be tested was that evidence of psychological morbidity, particularly fear-avoidance behavior, would be manifest from the outset of the presenting attack in susceptible subjects. SUMMARY OF BACKGROUND DATA: While back pain is an almost universal human experience, only about 5% of sufferers seek medical advice. Most of these respond to conservative treatment. However, approximately 10% of those who experience an acute attack of low back pain go on to become chronic sufferers. METHODS: Psychosocial and physiological data (including fear-avoidance measures) were collected from a sample of 300 acute low back pain patients within 1 week of presentation and at 2 months, to try to predict 12 month outcome. RESULTS: Data analysis showed that subjects who had not recovered by 2 months were those who went on to become chronic low back pain patients (7.3%). Using multiple regression analyses, fear-avoidance variables were the most successful in predicting outcome. Using multiple discriminant function analyses, the results suggest that the outcome in terms of the future course of low back pain can be correctly classified in 66% from fear-avoidance variables alone and in 88% of patients from all variables. CONCLUSIONS: The results suggest that, at the earliest stage of low back pain, fear of pain should be identified by clinicians and, where this is severe, pain confrontation should arguably form part of the approach to treatment.

Relationship between oxygen uptake, stroke rate and swimming velocity in competitive swimming.

The purpose of this study was to determine the relationship between oxygen demand, stroke rate and swimming velocity in competitive swimmers. The subjects who volunteered for this study were ten trained male swimmers (age, 16.7 +/- 0.4 yrs). VO2peak, swimming velocities at 80% (V80% VO2peak) and 100% (V100% VO2peak) of VO2peak and swimming velocity at the onset of blood lactate accumulation (VOBLA) were determined during a swimming economy profile test in a swimming flume. In the swimming economy test, determined by studying the relationship between oxygen uptake and swimming velocity cubed, the subjects were instructed to swim for six minutes at five or six submaximal swimming velocities. Steady-state oxygen uptake and stroke rate were calculated during the final two minutes of swimming. Results indicated that there were significant correlations between oxygen uptake and swimming velocity cubed (r = 0.963 to 0.998, p < 0.01), between oxygen uptake and stroke rate (r = 0.925 to 0.998, p < 0.01) and between stroke rate and swimming velocity cubed (r = 0.897, p < 0.05; to 0.994, p < 0.01) for all subjects. Furthermore, it was found that the slopes of the regression lines between oxygen uptake and swimming velocity cubed and between oxygen demand and stroke rate were significantly correlated to swimming performance indices (V80% VO2peak, V100% VO2peak and VOBLA). The results of this study suggest that the slope of the regression line between oxygen uptake and stroke rate can be utilized as an effective index of evaluating swimming performance.

The influence of age and gender on lumbar spine sagittal plane range of motion. A study of 1126 healthy subjects.

Inclinometers have been recommended for the measurement of lumbar spine range of motion (ROM) in the assessment of disability. Range of motion thresholds that determine impairment ratings have been established without regard to age and gender or variances of the measures. This investigation determined the effect of gender and age on lumbar spine sagittal plane ROM in 1126 healthy male and female volunteers. Results indicate that distinct differences exist between men and women in flexion angle and extension angle, whereas little difference exists between genders for total lumbar sagittal ROM. Total sagittal ROM, flexion angle, and extension angle declined as age increased. Because of the high degree of variability in the measurements, detecting impairment in ROM with this method is problematic.

The effects of nonswimming water exercises on older adults.

Exercise in a water medium reduces weight-bearing stresses on the skeletal joints, which may be advantageous for older individuals needing rehabilitation. The purpose of this study was to determine the effects of nonswimming exercises on muscle endurance, % body fat, and aerobic work capacity of an older adult population. Twelve subjects were in an exercise group (10 females and two males), and eight were in a control group (five females and three males). The mean ages of the groups were 65 (+/- 5.29) years and 56 (+/- 6.78) years, respectively. Before and after 12 weeks of training, subjects were measured three times weekly for resting heart rate, maximum heart rate, VO2 max, body composition, and work capacity in water. A general linear model ANCOVA was used with age as the covariate. The exercise group improved significantly (p < .05) on all dependent variables examined except body composition after 12 weeks. However, the control group experienced no significant changes on any variable over this period. In the comparisons between groups, the exercise group significantly surpassed the control group on all variables except body composition, where neither group experienced change. Nonswimming exercises appear to be a viable and effective means to improve cardiorespiratory function and physical work capacity of the elderly.

Physiological and spinal responses to circuit weight-training.

Physiological, perceptual and physical responses to a typical circuit weight-training (CWT) regimen were recorded in two studies. The aims were to assess the intensity of exercise during CWT; and to determine whether physical responses as evaluated by spinal shrinkage were related to physiological and perceptual responses to CWT. In the first study (n = 10) heart rate (HR), oxygen consumption (VO2), ventilation (VE), blood lactate (La) and perceived exertion (RPE) were measured in response to CWT. Mean (+/- SD) time to complete three circuits of CWT was 17.8 (+/- 1.4) min. The HR max, VO2 max and peak La, measured first during an incremental treadmill test, were 195 (+/- 13) beats.min-1, 59.7 (+/- 4.8) ml.kg-1.min-1 and 14.3 (+/- 3.5) mM respectively. Mean HR and VO2 during CWT were 69% and 50% of the respective maximal values. The HR-VO2 ratio observed on the treadmill was elevated during CWT, with VO2 being lowered relative to HR. Mean VE and La values were 52.7 (+/- 14.5) l.min-1 and 6.9 (+/- 3.6) mM. The effect of the same CWT regimen on spinal loading as indicated by change in stature (shrinkage) was investigated in a second study (n = 8). The mean (+/- SD) time taken to complete the circuit was 17.4 (+/- 1.3) min. Mean shrinkage due to CWT (2.5 +/- 1.5 mm) was unrelated to the time taken to complete the circuits, to HR, RPE or to low back pain ratings (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A survey of interfering shoulder pain in United States competitive swimmers.

The prevalence of shoulder pain in United States competitive swimmers has not been extensively surveyed but is perceived as common. To evaluate this concern, a questionnaire survey was conducted on 1262 United States swimmers: 993 age group, 198 senior development, and 71 national team athletes. We sought to identify the incidence of interfering shoulder pain in this population and how it is influenced by various training tasks. The prevalence of current shoulder pain in these groups varied between 10% (age group) to 26% (national team) and increased with time in the sport. In those athletes with a painful shoulder, weight training, use of hand paddles, kickboard use, stretching, and various resistance activities aggravated the painful shoulder. This survey has identified that interfering shoulder pain is present in a substantial number of competitive swimmers.

Biomechanically and electromyographically assessed load on the spine in self-paced and force-paced lifting work.

The purpose of this study was to measure dose of spinal load when different pacing methods were applied to lifting work and to develop methodology for such measurements. The compressive load on the spine computed by a dynamic biomechanical model and the electromyographic activity of back muscles were used for describing the spinal load. Five men and five women worked in a laboratory on two days lifting a box up and down for 30 min on both days, on one day force-paced (4 lifts/min), and on the other self-paced in random order. The weight of the box was rated by the subjects to be acceptable for the work done. The lift rate of our female subjects was higher and that of the male subjects lower in self-paced than in force-paced work. There were no significant differences in peak lumbosacral compressions nor in the amplitude distributions of electromyography between the two pacing methods. The biomechanically-calculated compressive forces on the spine were lower (about 2.7 kN for the men and 2.3 kN for women) than the biomechanical recommendations for safe lifting, but the EMG activity showed quite high peaks so that for 1% of work time the activity was on women above 60% and on men above 40% of the activity during maximum isometric voluntary test contraction.

Shrinkage and psychophysical load ratings in self-paced and force-paced lifting work and during recovery.

The purpose of this study was to investigate the effects of the load on the human spine during force-paced and self-paced lifting and subsequent rest. Five women and five men worked under self-paced and force-paced (4 lifts/min) conditions on two days lifting a box for 30 min. The weight of the box was determined by the rating of acceptable load (RAL) method. During the work the lift rate was observed, and subjects made rating of perceived exertion (RPE) in 5 min intervals. The stature was measured with a staturemeter before and after the work period and during the following 30 min rest lying. In self-paced work women had a higher lift rate than men (p less than 0.05). In general, RPEs increased towards the end of the lifting period but RPEs did not differ between women and men or between self-paced and force-paced work. The mean shrinkage during the 30 min work was in self-paced work 5.1 +/- 2.0 mm for women and 5.8 +/- 1.2 mm for men, and in force-paced work 5.8 +/- 2.3 mm and 6.8 +/- 2.2 mm, respectively. There were no significant differences in shrinkage at work between women and men nor between the two different pacing methods. During the 30 min rest recumbent the subjects regained almost the same amount of height as they had lost during lifting. The rapid shrinkage and recovery when loading and unloading suggest that a few minutes rest lying after heavy activities would be beneficial for the spine.