Vascular Ageing and Exercise: Focus on Cellular Reparative Processes

Ageing is associated with an increased risk of developing noncommunicable diseases (NCDs), such as diabetes and cardiovascular disease (CVD). The increased risk can be attributable to increased prolonged exposure to oxidative stress. Often, CVD is preceded by endothelial dysfunction, which carries with it a proatherothrombotic phenotype. Endothelial senescence and reduced production and release of nitric oxide (NO) are associated with “vascular ageing” and are often accompanied by a reduced ability for the body to repair vascular damage, termed “reendothelialization.” Exercise has been repeatedly shown to confer protection against CVD and diabetes risk and incidence. Regular exercise promotes endothelial function and can prevent endothelial senescence, often through a reduction in oxidative stress. Recently, endothelial precursors, endothelial progenitor cells (EPC), have been shown to repair damaged endothelium, and reduced circulating number and/or function of these cells is associated with ageing. Exercise can modulate both number and function of these cells to promote endothelial homeostasis. In this review we look at the effects of advancing age on the endothelium and these endothelial precursors and how exercise appears to offset this “vascular ageing” process

The impact of inclusion, dose and duration of pyrazinamide (PZA) on efficacy and safety outcomes in tuberculosis: systematic review and meta-analysis protocol

BACKGROUND:Pyrazinamide (PZA) is a key component of current and future regimens for tuberculosis (TB). Inclusion of PZA at higher doses and for longer durations may improve efficacy outcomes but must be balanced against the potential for worse safety outcomes. METHODS:We will search for randomised and quasi-randomised clinical trials in adult participants with and without the inclusion of PZA in TB treatment regimens in the Cochrane infectious diseases group's trials register, Cochrane central register of controlled trials (CENTRAL), MEDLINE, EMBASE, LILACS, the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) international clinical trials registry platform. One author will screen abstracts and remove ineligible studies (10% of which will be double-screened by a second author). Two authors will review full texts for inclusion. Safety and efficacy data will be extracted to pre-piloted forms by one author (10% of which will be double-extracted by a second author). The Cochrane risk of bias tool will be used to assess study quality. The study has three objectives: the association of (1) inclusion, (2) dose and (3) duration of PZA with efficacy and safety outcomes. Risk ratios as relative measures of effect for direct comparisons within trials (all objectives) and proportions as absolute measures of effect for indirect comparisons across trials (for objectives 2 and 3) will be calculated. If there is insufficient data for direct comparisons within trials for objective 1, indirect comparisons between trials will be performed. Measures of effect will be pooled, with corresponding 95% confidence intervals and p values. Meta-analysis will be performed using the generalised inverse variance method for fixed effects models (FEM) or the DerSimonian-Laird method for random effects models (REM). For indirect comparisons, meta-regression for absolute measures against dose and duration data will be performed. Heterogeneity will be quantified through the I2-statistic for direct comparisons and the τ2 statistic for indirect comparisons using meta-regression. DISCUSSION:The current use of PZA for TB is based on over 60 years of clinical trial data, but this has never been synthesised to guide rationale use in future regimens and clinical trials. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019138735

Blood flow restriction exercise attenuates the exercise-induced endothelial progenitor cells in healthy, young men.

Endothelial progenitor cells (EPCs) are a vasculogenic subset of progenitors, which play a key role in maintenance of endothelial integrity. These cells are exercise-responsive, and thus exercise may play a key role in vascular repair and maintenance via mobilization of such cells. Blood flow restriction exercise, due to the augmentation of local tissue hypoxia, may promote exercise-induced EPC mobilization. Nine, healthy, young (18-30yrs) males participated in the study. Participants undertook 2 trials of single leg knee extensor (KE) exercise, at 60% of thigh occlusion pressure (4 sets at 30% maximal torque) (BFR) or non- blood flow restricted (non-BFR), in a fasted state. Blood was taken prior, immediately after, and 30 minutes after exercise. Blood was used for the quantification of haematopoietic progenitor cells (HPCs: CD34+CD45dim), EPCs (CD34+VEGFR2+/CD34+CD45dimVEGFR2+) by flow cytometry. Our results show that unilateral KE exercise did not affect circulating HPC levels (p = 0.856), but did result in increases in both CD34+VEGFR2+ and CD34+CD45dimVEGFR2+ EPCs, but only in the non-BFR trial (CD34+VEGFR2+: 269 ± 42 cells·mL-1 to 573 ± 90 cells·mL-1, pre- to immediately post-exercise, p = 0.008; CD34+CD45dimVEGFR2+: 129 ± 21 cells·mL-1 to 313 ± 103 cells·mL-1, pre- to 30 min post-exercise, p = 0.010). In conclusion, low intensity BFR exercise did not result in significant circulating changes in EPCs in the post-exercise recovery period and may impair exercise-induced EPC mobilization compared to non-BFR exercise

Elite mountain bike enduro competition: a study of rider hand-arm vibration exposure

Limited information is currently available regarding the hand-arm vibration (HAV) exposure 5 for professional off-road cyclists. Previous reports have suggested that commuting and 6 recreational cyclists are at risk of exceeding exposure limit values (ELV) in a single ride. 7 Therefore, further investigation of HAV exposure in competitive mountain biking is 8 warranted. Partial and total eight hour exposure data (Ai(8), A(8), ms⁻²) were computed for a 9 national level mountain bike enduro competitions. Hand-arm vibrations were measured using 10 a tri-axial accelerometer recording at a frequency of 3.2 kHz mounted on the handlebar and 11 accelerations were quantified after frequency weighting filters were applied (Wh). The data 12 presented shows that HAV exposure during one day of competitive enduro mountain bike 13 racing exceeds ELV (mean race exposure = 5.84 ms⁻² , minimum = 5.47ms⁻² , maximum = 14 6.61ms⁻²) and is greater than the HAV exposure observed in recreational cycling. This 15 suggests that further work is required to determine the exposure associated with changes in 16 equipment, technique and international racing events in professional athletes