Mobile application-assisted graded exercise practical: a remote teaching strategy to promote motivation and experiential learning in exercise physiology.

Practical classes are critical instructional activities in facilitating learning and motivation in health sciences education. With increasing pedagogical activities being conducted in virtual or remote settings, this study assessed how a remote practical assisted by physiological monitoring smartphone applications impacted student motivation and the achievement of intended learning outcomes in exercise physiology teaching. A total of 24 students (out of 30; 80%) were surveyed via a mixed-methods questionnaire containing 27 closed-ended, and 3 the traditional in-class practical in randomized order. Unpaired Student's t tests were performed for comparisons between interventions with a significance level set at P < 0.05. Students reported that both remote and in-class practicals strongly facilitated the achievement of learning outcomes. Self-reported scores for student satisfaction and perceived achievement of learning outcomes were similar between the two practical methodologies. Student motivation scores assessed using the Lab Motivation Scale revealed that students were more motivated during the remote practical, particularly in the effort domain (P < 0.05). This was in line with the identified themes from the qualitative responses that indicated that the remote practical was more engaging than the in-person practical, with greater opportunities for experiential learning and class involvement being the main factors underlying these findings. Taken together, remote practicals can be critical aspects of a blended learning curriculum that encourages student engagement and experiential learning. With further advancements in physiological monitoring wearables and smartphone technologies, remote practicals can be potential alternatives to traditional in-person practicals in exercise physiology teaching.NEW & NOTEWORTHY Remote practical classes, supported by physiological monitoring smartphone applications, were assessed for their utility in facilitating learning and raising student motivation in health sciences education in this study. A comparison of remote practicals with traditional in-class practicals revealed that a remote practical is an effective method for reinforcing physiology learning objectives with the added advantage of increased student motivation. The added value of remote practicals may be attributed to more experiential learning opportunities and increased engagement levels.

Serine-70 phosphorylated Bcl-2 prevents oxidative stress-induced DNA damage by modulating the mitochondrial redox metabolism.

Bcl-2 phosphorylation at serine-70 (S70pBcl2) confers resistance against drug-induced apoptosis. Nevertheless, its specific mechanism in driving drug-resistance remains unclear. We present evidence that S70pBcl2 promotes cancer cell survival by acting as a redox sensor and modulator to prevent oxidative stress-induced DNA damage and execution. Increased S70pBcl2 levels are inversely correlated with DNA damage in chronic lymphocytic leukemia (CLL) and lymphoma patient-derived primary cells as well as in reactive oxygen species (ROS)- or chemotherapeutic drug-treated cell lines. Bioinformatic analyses suggest that S70pBcl2 is associated with lower median overall survival in lymphoma patients. Empirically, sustained expression of the redox-sensitive S70pBcl2 prevents oxidative stress-induced DNA damage and cell death by suppressing mitochondrial ROS production. Using cell lines and lymphoma primary cells, we further demonstrate that S70pBcl2 reduces the interaction of Bcl-2 with the mitochondrial complex-IV subunit-5A, thereby reducing mitochondrial complex-IV activity, respiration and ROS production. Notably, targeting S70pBcl2 with the phosphatase activator, FTY720, is accompanied by an enhanced drug-induced DNA damage and cell death in CLL primary cells. Collectively, we provide a novel facet of the anti-apoptotic Bcl-2 by demonstrating that its phosphorylation at serine-70 functions as a redox sensor to prevent drug-induced oxidative stress-mediated DNA damage and execution with potential therapeutic implications.

Thermoregulation in the Aging Population and Practical Strategies to Overcome a Warmer Tomorrow.

As global temperatures continue to rise, improving thermal tolerance in the aged population is crucial to counteract age-associated impairments in thermoregulatory function. Impairments in reflex cutaneous vasodilation and sweating response can augment the vulnerability of older adults to heat-related injuries following exposure to heat stress. Mechanisms underlying a compromised cutaneous vasodilation are suggested to include reduced sympathetic neural drive, diminished cholinergic co-transmitter contribution, and altered second messenger signaling events. On the other hand, impairments in sweating response are ascribed to reduced sweat gland cholinergic sensitivity and altered cyclooxygenase and nitric oxide signaling. Several practical mitigation strategies such as exercise, passive heating, and behavioral adaptations are proposed as means to overcome heat stress and improve thermal tolerance in the aged. Aerobic exercise training is shown to be amongst the most effective ways to enhance thermoregulatory function. However, in elderly with limited exercise capability due to chronic diseases and mobility issues, passive heating can serve as a functional alternative as it has been shown to confer similar benefits to that of exercise training. Supplementary to exercise training and passive heating, behavioral adaptations can be applied to further enhance the heat-preparedness of the aged.

Ser70 phosphorylation of Bcl-2 by selective tyrosine nitration of PP2A-B56δ stabilizes its antiapoptotic activity.

Bcl-2 is frequently overexpressed in hematopoietic malignancies, and selective phosphorylation at ser70 enhances its antiapoptotic activity. Phospho-ser70 is dephosphorylated by specific heterotrimers of protein phosphatase 2A (PP2A). We report here that a mild pro-oxidant intracellular milieu induced by either pharmacological inhibition or genetic knockdown of superoxide dismutase 1 (SOD1) inhibits the functional holoenzyme assembly of PP2A and prevents Bcl-2 ser70 dephosphorylation. This redox-dependent regulation of Bcl-2 phosphorylation is due to nitrosative modification of B56δ, which we identify as the regulatory subunit mediating PP2A-dependent Bcl-2 dephosphorylation. Redox inhibition of PP2A results from peroxynitrite-mediated nitration of a conserved tyrosine residue within B56δ (B56δ(Y289)). Although nitrated B56δ(Y289) binds efficiently to ser70-phosphorylated Bcl-2, this specific modification inhibits the recruitment of the PP2A catalytic core (A and C subunits). Furthermore, inhibition of B56δ(Y289) nitration restores PP2A holoenzyme assembly, thereby permitting S70 dephosphorylation of Bcl-2 and inhibiting its antiapoptotic activity. More important, in primary cells derived from clinical lymphomas, Bcl-2 phosphorylation at S70 directly correlates with B56δ nitration and repression of SOD1, but inversely correlates with B56δ interaction with the PP2A-C catalytic subunit. These data underscore the role of a pro-oxidant milieu in chemoresistance of hematopoietic and other cancers via selective targeting of tumor suppressors such as PP2A.

External auricle temperature enhances ear-based wearable accuracy during physiological strain monitoring in the heat.

Body core temperature (Tc) monitoring is crucial for minimizing heat injury risk. However, validated strategies are invasive and expensive. Although promising, aural canal temperature (Tac) is susceptible to environmental influences. This study investigated whether incorporation of external auricle temperature (Tea) into an ear-based Tc algorithm enhances its accuracy during multiple heat stress conditions. Twenty males (mean ± SD; age = 25 ± 3 years, BMI = 21.7 ± 1.8, body fat = 12 ± 3%, maximal aerobic capacity (VO2max) = 64 ± 7 ml/kg/min) donned an ear-based wearable and performed a passive heating (PAH), running (RUN) and brisk walking trial (WALK). PAH comprised of immersion in hot water (42.0 ± 0.3 °C). RUN (70 ± 3%VO2max) and WALK (50 ± 10%VO2max) were conducted in an environmental chamber (Tdb = 30.0 ± 0.2 °C, RH = 71 ± 2%). Several Tc models, developed using Tac, Tea and heart rate, were validated against gastrointestinal temperature. Inclusion of Tea as a model input improved the accuracy of the ear-based Tc algorithm. Our best performing model (Trf3) displayed good group prediction errors (mean bias error = - 0.02 ± 0.26 °C) but exhibited individual prediction errors (percentage target attainment ± 0.40 °C = 88%) that marginally exceeded our validity criterion. Therefore, Trf3 demonstrates potential utility for group-based Tc monitoring, with additional refinement needed to extend its applicability to personalized heat strain monitoring.

Effects of Heat Exposure and Ice Slurry Ingestion on Risk-Taking Behavior in Healthcare Workers.

PURPOSE: Healthcare workers (HCWs) wearing personal protective equipment (PPE) experience physiological strain that can impair motor and psychological functions, potentially affecting patient care. We assessed the effects of heat exposure on maximal strength and risk-taking behavior amongst PPE-wearing HCWs and the efficacy of ice slurry to alleviate adverse effects. METHODS: 17 HCWs completed two experimental trials in a crossover design, consuming 5 g × kg-1 of body mass of ambient drink (AMB) or ice slurry (ICE) before donning PPE and undergoing 2-h of simulated decontamination exercise (wet-bulb globe temperature (WBGT): 25.9 ± 0.8 °C, PPE microenvironment WBGT: 29.1 ± 2.1 °C). Body core temperature (Tc), heart rate (HR), chest skin temperature (Tsk), ratings of perceived exertion (RPE), thermal sensation (RTS), maximal voluntary contraction (MVC), risk-taking behavior (Balloon Analogue Risk-Taking task; BART) and salivary cortisol were assessed. RESULTS: Pre- to post-drinking ∆Tc was greater in ICE (-0.2 ± 0.1 °C) than AMB (-0.0 ± 0.1 °C, P = 0.003). Post-drinking RTS was lower in ICE (2.7 ± 1.2) than AMB (4.1 ± 0.4, P < 0.001). ICE and AMB had similar Tc and HR (both P > 0.05), but Tsk was lower in ICE than AMB (P = 0.049). A lower MVC (30.3 ± 6.7 kg vs 27.4 ± 4.9 kg, P = 0.001) and higher BART adjusted total pump count (472 ± 170 pumps vs 615 ± 174 pumps, P = 0.017) was observed pre- to post-trial in AMB but absent in ICE (both P > 0.05). Salivary cortisol was similar between trials (P = 0.42). CONCLUSIONS: Heat-exposed PPE-wearing HCWs had impaired maximal strength and elevated risk-taking behavior. This may increase the risk of avoidable workplace accidents that can jeopardize HCWs and patient care. Ice slurry ingestion alleviated these heat-related impairments, suggesting its potential as an ergogenic aid.

Regulation of mitochondrial metabolism: yet another facet in the biology of the oncoprotein Bcl-2.

The Bcl-2 (Bcl is B-cell lymphocytic-leukaemia proto-oncogene) family comprises two groups of proteins with distinct functional biology in cell-fate signalling. Bcl-2 protein was the first member to be discovered and associated with drug resistance in human lymphomas. Since then a host of other proteins such as Bcl-xL, Bcl-2A1 and Mcl-1 with similar anti-apoptotic functions have been identified. In contrast, the pro-apoptotic Bcl-2 proteins contain prototypic effector proteins such as Bax and Bak, and the BH3 (Bcl-2 homology)-only proteins comprising Bak, Bid, Bim, Puma and Noxa. A complex interplay between the association of pro-apoptotic and anti-apoptotic proteins with each other determines the sensitivity of cancer cells to drug-induced apoptosis. The canonical functional of Bcl-2 in terms of apoptosis inhibition is its ability to prevent mitochondrial permeabilization via inhibiting the translocation and oligomerization of pro-apoptotic proteins such as Bax; however, more recent evidence points to a novel mechanism of the anti-apoptotic activity of Bcl-2. Overexpression of Bcl-2 increases mitochondrial oxygen consumption and in doing so generates a slight pro-oxidant intracellular milieu, which promotes genomic instability and blocks death signalling. However, in the wake of overt oxidative stress, Bcl-2 regulates cellular redox status thereby preventing excessive build-up of ROS (reactive oxygen species), which is detrimental to cells and tissues. Taken together, the canonical and non-canonical activities of Bcl-2 imply a critical involvement of this protein in the processes of tumour initiation and progression. In the present paper we review these functionally distinct outcomes of Bcl-2 expression with implications for the chemotherapeutic management of cancers.

Efficacy of Isothermic Conditioning over Military-Based Heat Acclimatization and Interval Training in Tropical Native Males.

PURPOSE: We compared the effectiveness of three field-based training programs, namely military-based heat acclimatization (MHA), isothermic conditioning (IC) and interval training (IT), in inducing physiological adaptations in tropical natives. METHODS: Fifty-one untrained tropical native males (mean ± standard deviation: age, 25 ± 2 yr; body mass index, 23.6 ± 3.2 kg·m -2 ; body fat, 19% ± 5%; 2.4-km run time, 13.2 ± 0.9 min) donned the Full Battle Order attire (22 kg) and performed a treadmill route march heat stress test in an environmental chamber (dry bulb temperature, 29.9°C ± 0.5°C; relative humidity, 70% ± 3%). Heat stress tests were conducted before (PRE) and after (POST) a 2-wk training intervention consisting of either a MHA ( n = 17, 10 sessions of military-based heat acclimatization), IC ( n = 17, 10 sessions with target gastrointestinal temperature ( Tgi ) ≥ 38.5°C) or IT ( n = 17, six sessions of high-intensity interval training) program. Tgi , HR, mean weighted skin temperature ( Tsk ), physiological strain index (PSI) and thigh-predicted sweat sodium concentration ([Na + ]) were measured and analyzed by one-factor and two-factor mixed design ANOVA with a 0.05 level of significance. RESULTS: Field-based IC induced a greater thermal stimulus than MHA ( P = 0.029) and IT ( P < 0.001) during training. Reductions in mean exercise Tgi (-0.2°C [-0.3°C, 0.0°C]; P = 0.009) , PSI (-0.4 [-0.7, -0.1]; P = 0.015) and thigh-predicted sweat [Na + ] (-9 [-13, -5 mmol·L -1 ]; P < 0.001) were observed in IC but not MHA and IT (all P > 0.05). Resting HR (MHA, -4 bpm [-7, 0 bpm]; P = 0.025; IC, -7 bpm [-10, -4 bpm]; P < 0.001; IT, -4 bpm [-8, -1 bpm]; P = 0.008) and mean exercise HR (MHA, -4 [-8, 0 bpm]; P = 0.034; IC, -11 bpm [-15, -8 bpm]; P < 0.001, IT = -5 bpm [-9, -1 bpm]; P = 0.012) were lowered in all groups after training. Isothermic conditioning elicited a greater attenuation in mean exercise HR and thigh-predicted sweat [Na + ] relative to MHA (both P < 0.05). No between-group differences were observed when comparing MHA and IT (all P > 0.05). CONCLUSIONS: Isothermic conditioning induced a more complete heat-adapted phenotype relative to MHA and IT. Interval training may serve as a time efficient alternative to MHA.

Assessment of dehydration using body mass changes of elite marathoners in the tropics.

OBJECTIVES: The ACSM recommends drinking to avoid loss of body mass >2% during exercise to avert compromised performance. Our study aimed to assess the level of dehydration in elite runners following a city marathon in a tropical environment. DESIGN: Prospective cohort design. METHODS: Twelve elite runners (6 males, 6 females; age 24-41 y) had body mass measured to the nearest 0.01kg in their race attire immediately before and after the 2017 Standard Chartered Singapore Marathon 2017. Body mass change was corrected for respiratory water loss, gas exchange, and sweat retained in clothing, and expressed as % of pre-race mass (i.e. % dehydration). RESULTS: Data are expressed as means±SD (range). Dry bulb temperature and humidity were 27.9±0.1°C (27.4-28.3°C) and 79±2% (73-82%). Finish time was 155±10min (143-172min). Male runners finishing positions ranged from 2-12 out of 7627 finishers, whilst female runners placed 1-8 out of 1754 finishers. Body mass change (loss) and % dehydration for all runners were 2.5±0.5kg (1.8-3.5kg) and 4.6±0.9% (3.6-6.8%). Male runners experienced body mass loss of 2.8±0.5kg and 4.9±1.2% while females experienced body mass loss of 2.1±0.2kg and 4.3±0.6%. CONCLUSIONS: Despite experiencing dehydration (4.6% body mass loss) two-fold higher than current fluid replacement guidelines recommend (≤2%), elite male and female runners performed successfully and without medical complication in a hot weather marathon.

Heart Rate Measures From Wrist-Worn Activity Trackers in a Laboratory and Free-Living Setting: Validation Study.

BACKGROUND: Wrist-worn activity trackers are popular, and an increasing number of these devices are equipped with heart rate (HR) measurement capabilities. However, the validity of HR data obtained from such trackers has not been thoroughly assessed outside the laboratory setting. OBJECTIVE: This study aimed to investigate the validity of HR measures of a high-cost consumer-based tracker (Polar A370) and a low-cost tracker (Tempo HR) in the laboratory and free-living settings. METHODS: Participants underwent a laboratory-based cycling protocol while wearing the two trackers and the chest-strapped Polar H10, which acted as criterion. Participants also wore the devices throughout the waking hours of the following day during which they were required to conduct at least one 10-min bout of moderate-to-vigorous physical activity (MVPA) to ensure variability in the HR signal. We extracted 10-second values from all devices and time-matched HR data from the trackers with those from the Polar H10. We calculated intraclass correlation coefficients (ICCs), mean absolute errors, and mean absolute percentage errors (MAPEs) between the criterion and the trackers. We constructed decile plots that compared HR data from Tempo HR and Polar A370 with criterion measures across intensity deciles. We investigated how many HR data points within the MVPA zone (≥64% of maximum HR) were detected by the trackers. RESULTS: Of the 57 people screened, 55 joined the study (mean age 30.5 [SD 9.8] years). Tempo HR showed moderate agreement and large errors (laboratory: ICC 0.51 and MAPE 13.00%; free-living: ICC 0.71 and MAPE 10.20%). Polar A370 showed moderate-to-strong agreement and small errors (laboratory: ICC 0.73 and MAPE 6.40%; free-living: ICC 0.83 and MAPE 7.10%). Decile plots indicated increasing differences between Tempo HR and the criterion as HRs increased. Such trend was less pronounced when considering the Polar A370 HR data. Tempo HR identified 62.13% (1872/3013) and 54.27% (5717/10,535) of all MVPA time points in the laboratory phase and free-living phase, respectively. Polar A370 detected 81.09% (2273/2803) and 83.55% (9323/11,158) of all MVPA time points in the laboratory phase and free-living phase, respectively. CONCLUSIONS: HR data from the examined wrist-worn trackers were reasonably accurate in both the settings, with the Polar A370 showing stronger agreement with the Polar H10 and smaller errors. Inaccuracies increased with increasing HRs; this was pronounced for Tempo HR.

Mitochondrial ROS and involvement of Bcl-2 as a mitochondrial ROS regulator.

Mitochondria are the major intracellular source of reactive oxygen species (ROS). While excessive mitochondrial ROS (mitoROS) production induces cell injury and death, there is accumulating evidence that non-toxic low levels of mitoROS could serve as important signaling molecules. Therefore, maintenance of mitoROS at physiological levels is crucial for cell homeostasis as well as for survival and proliferation. This review describes the various mechanisms that keep mitoROS in check, with particular focus on the role of the onco-protein Bcl-2 in redox regulation. In addition to its canonical anti-apoptotic activity, Bcl-2 has been implicated in mitoROS regulation by its effect on mitochondrial complex IV activity, facilitating the mitochondrial incorporation of GSH and interaction with the small GTPase-Rac1 at the mitochondria. We also discuss some of the plausible mechanism(s) which allows Bcl-2 to sense and respond to the fluctuations in mitoROS.

Bcl-2: a prime regulator of mitochondrial redox metabolism in cancer cells.

SIGNIFICANCE: Mitochondria play a critical role as death amplifiers during drug-induced apoptosis in cancer cells by providing pro-apoptotic factors that are released from the mitochondrial inter-membranous space upon the induction of mitochondrial outer membrane permeabilization. This intrinsic death signaling pathway is the preferred mechanism employed by most anticancer compounds, and as such, resistance to drug-induced apoptosis is invariably associated with inhibition of mitochondrial death signaling network. The latter is a function of a balance between the pro- and the anti-apoptotic members of the Bcl-2 family. Bcl-2 is the prototype anti-apoptotic protein that localizes to the mitochondria and blocks the recruitment and activation of pro-apoptotic proteins, such as Bax, to the mitochondria. RECENT ADVANCES AND CRITICAL ISSUES: Recent evidence has highlighted a novel mechanism of anti-apoptotic activity of Bcl-2 in addition to its canonical activity in regulating mitochondrial outer membrane permeabilization. This novel activity is a function of cellular redox regulation, in particular, mitochondrial metabolism in cancer cells. FUTURE DIRECTIONS: Here we review the current state of our understanding of the death inhibitory activity of Bcl-2 and provide insight into the novel functional biology of this remarkable protein, which could have implications for designing innovative strategies to overcome the problem of drug resistance in the clinical settings.

Bcl-2 modulates resveratrol-induced ROS production by regulating mitochondrial respiration in tumor cells.

Resveratrol is a naturally occurring flavanoid with potent apoptosis-inducing activity against human tumor cells. We investigated the effect of resveratrol on human leukemia cell lines, in particular its ability to induce intracellular reactive oxygen species production and the effect of Bcl-2 overexpression on this model. Exposure of CEM cells to increasing concentrations of resveratrol (0-50 microM) resulted in an increase in mitochondrial superoxide production, decrease in transmembrane potential, and a concomitant decrease in cell viability. Whereas overexpression of Bcl-2 increased mitochondrial oxygen consumption and complex IV activity, CEM/Bcl-2 cells responded to the increased mitochondrial oxidative stress induced by resveratrol by significantly reducing mitochondrial respiration, complex IV activity, and O(2)(-) production, and promoted cell survival. The inhibitory effect of Bcl-2 on resveratrol-induced mitochondrial O(2)(-) production is further corroborated by the neutralization of this regulatory effect upon siRNA-mediated gene silencing of Bcl-2. These data provide evidence implicating mitochondrial metabolism in the anticancer activity of resveratrol, and underscore a novel regulatory role of Bcl-2 against exogenous oxidative stress through its ability to fine tune mitochondrial respiration, and by doing so maintaining mitochondrial O(2)(-) at a level optimal for survival.