Intervening on the Side Effects of Hormone-Dependent Cancer Treatment: The Role of Strength Training

While prostate and breast cancers are both highly prevalent and treatable using hormone suppression therapy, a constellation of side effects ensue, which mimic typical aging effects but at an accelerated pace. Because strength training is considered to be an intervention of choice for addressing the musculoskeletal and metabolic consequences of normal aging in older adults, it may be an effective intervention to attenuate or reverse the side effects of hormone-dependent cancer treatment. This paper provides an overview of the independent effects of strength training on common musculoskeletal and metabolic side effects of hormone-dependent therapy used for prostate and breast cancers. Strength training appears to be an effective complementary therapy for some of the adverse effects of prostate and breast treatment. Future research needs to address potential mechanisms to explain recent findings and to explore the role of strength training in addressing specific risk factors resulting from cancer treatment

Enhanced skeletal muscle ribosome biogenesis, yet attenuated mTORC1 and ribosome biogenesis-related signalling, following short-term concurrent versus single-mode resistance training

Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of ribosome biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT alone. Twenty-three males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor (45S pre-rRNA), and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT. However, during the final training session, RT further increased both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S pre-rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT induces further increases mTORC1 and ribosome biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in ribosome biogenesis markers were more favourable following a period of short-term concurrent training versus RT performed alon

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer

BackgroundReduced testosterone levels can influence immune system function, particularly T cells. Exercise during cancer reduces treatment-related side effects and provide a stimulus to mobilize and redistribute immune cells. However, it is unclear how conventional and unconventional T cells (UTC) respond to acute exercise in prostate cancer survivors compared to healthy controls.MethodsAge-matched prostate cancer survivors on androgen deprivation therapy (ADT) and those without ADT (PCa) along with non-cancer controls (CON) completed ∼45 min of intermittent cycling with 3 min at 60% of peak power interspersed by 1.5 min of rest. Fresh, unstimulated immune cell populations and intracellular perforin were assessed before (baseline), immediately following (0 h), 2 h, and 24 h post-exercise.ResultsAt 0 h, conventional T cell counts increased by 45%–64% with no differences between groups. T cell frequency decreased by −3.5% for CD3+ and −4.5% for CD4+ cells relative to base at 0 h with CD8+ cells experiencing a delayed decrease of −4.5% at 2 h with no group differences. Compared to CON, the frequency of CD8+CD57+ cells was −18.1% lower in ADT. Despite a potential decrease in maturity, ADT increased CD8+perforin+ GMFI. CD3+Vα7.2+CD161+ counts, but not frequencies, increased by 69% post-exercise while CD3+CD56+ cell counts increased by 127% and were preferentially mobilized (+1.7%) immediately following the acute cycling bout. There were no UTC group differences. Cell counts and frequencies returned to baseline by 24 h.ConclusionFollowing acute exercise, prostate cancer survivors demonstrate normal T cell and UTC responses that were comparable to CON. Independent of exercise, ADT is associated with lower CD8+ cell maturity (CD57) and perforin frequency that suggests a less mature phenotype. However, higher perforin GMFI may attenuate these changes, with the functional implications of this yet to be determined

The Effect of Yearly-Dose Vitamin D Supplementation on Muscle Function in Mice

Supplementation with vitamin D helps to alleviate weakness and fatigue seen with deficiency. However, large bolus doses appear to worsen the risk of falls. Whether this occurs as a direct result of muscle weakness is currently unknown. Thus, the aims of this study were to examine the muscle function following administration of high doses of vitamin D. Given the safety issues associated with bolus doses, experiments were conducted on C57BL6 mice. Mice at eight weeks of age with otherwise normal levels of vitamin D were supplemented for four weeks with a high dose (HIGH; n = 12) of vitamin D (20000 IU/kg food) designed to provide a year’s worth of vitamin D. These mice were compared to another group who received that same yearly dose in a single bolus i.p. injection (YEAR; n = 12). Mice provided with standard mouse chow, which contained 1000 IU/kg food, and injected with the vitamin D vehicle were used as controls (CON; n = 16). Force and fatigue properties of hind limb fast- and slow-twitch muscles were measured. CON animals ingested vitamin D consistent with typical human supplementation. HIGH animals consumed significantly more food than the CON animals, such that they ingested more than a year’s worth of vitamin D in four weeks. Despite this, there were few differences in the muscle function compared with CON. YEAR animals demonstrated lower absolute and relative forces in both muscles compared to the HIGH animals, as well as lower force during fatigue and early recovery. Large bolus doses of vitamin D appear to have detrimental effects on the skeletal muscle function, likely being a contributor to increased risk of falls observed with similar doses in humans. Mice ingesting the same amount over four weeks did not demonstrate the same deleterious effects, suggesting this may be a safe way to provide high vitamin D if required

Validity and reliability of lower-limb pulse-wave velocity assessments using an oscillometric technique

There is a growing interest in the deleterious effects of sedentary behaviour on lower-limb arterial health. To permit further investigation, including in larger epidemiological studies, there is a need to identify lower-limb arterial health assessment tools that are valid and reliable, yet simple to administer. Purpose: This study sought to determine the validity and between-day reliability of femoral-ankle pulse-wave velocity (faPWV) measures obtained using an oscillometric-based device (SphygmocCor XCEL) in supine and seated positions. Doppler ultrasound (US) was used as the criterion. Methods: A total of 47 healthy adults were recruited for validity (n=32) and reliability (n=15) analyses. Validity was determined by measuring faPWV in seated and supine positions using the XCEL and US devices, in a randomised order. Between-day reliability was determined by measuring seated and supine faPWV using the XCEL on 3 different mornings, separated by a maximum of 7 days. Results: The validity criteria (absolute standard error of estimate [aSEE] <1.0 m/s) was met in the supine (aSEE = 0.8 m/s, 95% CI: 0.4-1.0), but not the seated (aSEE = 1.2 m/s, 95 % CI: 1.1, 1.2) position. Intras-class correlation coefficient estimates revealed the XCEL demonstrated good reliability in the supine position (ICC=0.83, 95% CI: 0.65, 0.93), but poor reliability in the seated position (ICC = 0.29, 95% CI: 0.23, 0.63). Conclusions: The oscillometric XCEL device can be used to determine lower-limb PWV with acceptable validity and reliability in the conventionally recommended supine position, but not the seated position

Heat Acclimation with or without Normobaric Hypoxia Exposure Leads to Similar Improvements in Endurance Performance in the Heat

Background: Combining the key adaptation of plasma volume (PV) expansion with synergistic physiological effects of other acclimation interventions to maximise endurance performance in the heat has potential. The current study investigated the effects of heat acclimation alone (H), combined with normobaric hypoxia exposure (H+NH), on endurance athletic performance. Methods: Well-trained participants completed a heat-stress trial (30 °C, 80% relative humidity (RH), 20.8% fraction of inspired oxygen (FiO2)) of a 75 min steady-state cycling (fixed workload) and a subsequent 15 min cycling time trial for distance before and after intervention. Participants completed 12 consecutive indoor training days with either heat acclimation (H; 60 min·day−1, 30 °C, 80% RH; 20.8% FiO2) or heat acclimation and overnight hypoxic environment (H+NH; ~12 h, 60% RH; 16% FiO2 simulating altitude of ~2500 m). Control (CON) group trained outdoors with average maximum daily temperature of 16.5 °C and 60% RH. Results: Both H and H+NH significantly improved time trial cycling distance by ~5.5% compared to CON, with no difference between environmental exposures. PV increased (+3.8%) and decreased (−4.1%) following H and H+NH, respectively, whereas haemoglobin concentration decreased (−2%) and increased (+3%) in H and H+NH, respectively. Conclusion: Our results show that despite contrasting physiological adaptations to different environmental acclimation protocols, heat acclimation with or without hypoxic exposure demonstrated similar improvements in short-duration exercise performance in a hot environment

Effects of acute prolonged sitting on cerebral perfusion and executive function in young adults: a randomized cross-over trial

Exposure to acute prolonged sitting reportedly leads to decreased cerebral blood flow. However, it is unclear whether this exposure translates to decreased cerebral perfusion and executive function, or whether simple strategies to break-up sitting can maintain cerebral perfusion and executive function. This study sought to answer two questions: in young, healthy adults (i) does prolonged (3 h) sitting lead to decreased cerebral perfusion and executive function? and (ii) does breaking-up prolonged sitting, using intermittent calf raise exercises, prevent changes in cerebral perfusion and executive function? Twenty young, healthy participants (21.7 [2.5] y, 70% F, 25.5 [6.1] kg/m2) were randomized to: 3 h sitting with 10 calf raises every 10 min (CALF), and 3 h sitting without calf intermittent calf raises (CON). Prefrontal cortex perfusion was assessed using near-infrared spectroscopy to monitor total hemoglobin (tHB) concentration and tissue saturation index (TSI, oxygenated hemoglobin). Executive function was assessed using the Stroop Word and Color Tasks. Following 3 h sitting, tHb was significantly lower in CALF vs. CON (-2.1 μM, 95% CI: -3.1, -1.1). TSI was not significantly different between conditions (P = .667). Word (1.6 ms, 95% CI: 0.7, 2.5) and Color (1.3 ms, 95% CI: -0.2, 2.8) completion times were longer (worse) for CALF compared to CON. In conclusion, calf raises decreased both cerebral perfusion and executive function. Simple strategies, such as fidgeting or calf raises, which have been reported to preserve vascular function in the legs, appear not to be sufficient enough to benefit cerebral perfusion or executive function

The Promise of Prediction Markets

Prediction markets are markets for contracts that yield payments based on the outcome of an uncertain future event, such as a presidential election. Using these markets as forecasting tools could substantially improve decision making in the private and public sectors. We argue that U.S. regulators should lower barriers to the creation and design of prediction markets by creating a safe harbor for certain types of small stakes markets. We believe our proposed change has the potential to stimulate innovation in the design and use of prediction markets throughout the economy, and in the process to provide information that will benefit the private sector and government alike.Technology and Industry

MicroRNA markers for forensic body fluid identification obtained from microarray screening and quantitative RT-PCR confirmation

MicroRNAs (miRNAs) are non-protein coding molecules with important regulatory functions; many have tissue-specific expression patterns. Their very small size in principle makes them less prone to degradation processes, unlike messenger RNAs (mRNAs), which were previously proposed as molecular tools for forensic body fluid identification. To identify suitable miRNA markers for forensic body fluid identification, we first screened total RNA samples derived from saliva, semen, vaginal secretion, and venous and menstrual blood for the expression of 718 human miRNAs using a microarray platform. All body fluids could be easily distinguished from each other on the basis of complete array-based miRNA expression profiles. Results from quantitative reverse transcription PCR (RT-PCR; TaqMan) assays for microarray candidate markers confirmed strong over-expression in the targeting body fluid of several miRNAs for venous blood and several others for semen. However, no candidate markers from array experiments for other body fluids such as saliva, vaginal secretion, or menstrual blood could be confirmed by RT-PCR. Time-wise degradation of venous blood and semen stains for at least 1 year under lab conditions did not significantly affect the detection sensitivity of the identified miRNA markers. The detection limit of the TaqMan assays tested for selected venous blood and semen miRNA markers required only subpicogram amounts of total RNA per single RT-PCR test, which is considerably less than usually needed for reliable mRNA RT-PCR detection. We therefore propose the application of several stable miRNA markers for the forensic identification of blood stains and several others for semen stain identification, using commercially available TaqMan assays. Additional work remains necessary in search for suitable miRNA markers for other forensically relevant body fluids