Concurrent training

Many sports require a range of physical qualities including strength, power and aerobic capacity for optimal performance. Subsequently, training is likely to contain periods where concurrent development of fitness components is required and will typically be classified into two training categories, endurance and strength training. In order to optimize training, the interaction of these fitness components should be considered as endurance training may interfere with resistance training sessions via conflicting molecular signaling which may blunt optimal muscular development. At present, there is a range of conflicting recommendations in the literature due to the challenges of comparing different training studies and the variables which impact upon the magnitude of adaptation; including volume, intensity, sequencing, rest and concurrent training goals. Most importantly, the overall training stress should be considered to limit cumulative fatigue and minimize the potential negative effect on strength adaptations via dampened hypertrophic responses. Inter-session rest should be maximized wherever possible to reduce the interaction between competing molecular signaling pathways. Where required, strength training should be completed after aerobic endurance training to ensure overnight recovery facilitates strength based adaptations. Overall, optimal planning during concurrent training is a complex interaction between a range of variables where strength and conditioning professionals should be conscious of a range of factors and select a training regime that minimized the interference effect but also fits with their own training logistics

The effects of complex training on neuromuscular development of the lower limbs in youth netball players

Objective: The high prevalence of injury in netball can be associated with intrinsic or extrinsic factors. Female athletes have an increased risk of injury as they enter into maturity due to increased joint laxity and a reduction in neuromuscular control, resulting in altered landing biomechanics and greater knee joint injury risk. This study sought to investigate whether complex training (CT) could improve neuromuscular strength and landing kinematics, thereby reducing injury risk to the knee. Methods: A within subject, repeated measures design was utilised. Ten youth netball academy players (age, 15.3 ± 0.9, years; height, 169.0 ± 7.0, cm; body mass, 62.2 ± 6.9, kg) participated and attended one familiarisation and two testing sessions (pre- and post-intervention). Participants’ were assessed on: countermovement jump (CMJ), landing error score system (LESS), and single leg countermovement jump (SLCMJ) of both limbs. All participants engaged in a 6 week, one day per week, strength training and plyometric intervention for the lower limbs utilising CT. Results: Significant improvements were evidenced for CMJ height (p = 0.001, d = 1.2 “moderate” effect), CMJ peak power output (PPO) (p = 0.001, d = 0.7 “small” effect), LESS (p = 0.002, d = 1.7 “large” effect), and SLCMJ left height (p = 0.01, d = 1.2 “moderate” effect) following the intervention. Conclusion: Performing one CT session a week over 6 weeks enhanced kinematics and performance of jumping activities both bilaterally and unilaterally, it also brought about reductions in asymmetries in young female athletes

Survivin-T34A: molecular mechanism and therapeutic potential

Jonathan R Aspe, Nathan R WallCenter for Health Disparities Research and Molecular Medicine, Division of Biochemistry and Microbiology, Department of Basic Sciences, Loma Linda University, Loma Linda, CA, USAAbstract: The inhibitor of apoptosis protein survivin's threonine 34 to alanine (T34A) mutation abolishes a phosphorylation site for p34(cdc2)–cyclin B1, resulting in initiation of the mitochondrial apoptotic pathway in cancer cells; however, it has little known direct effects on normal cells. The possibility that targeting survivin in this way may provide a novel approach for selective cancer gene therapy has yet to be fully evaluated. Although a flurry of work was undertaken in the late 1990s and early 2000s, only minor advances on this mutant have recently taken place. We recently described that cells generated to express a stable form of the mutant protein released this survivin-T34A to the conditioned medium. When this conditioned medium was collected and deposited on naive tumor cells, conditioned medium T34A was as effective as some chemotherapeutics in the induction of tumor cell apoptosis, and when combined with other forms of genotoxic stressors potentiated their killing effects. We hope with this review to revitalize the T34A field, as there is still much that needs to be investigated. In addition to determining the therapeutic dose and the duration of drug therapy required at the disease site, a better understanding of other key factors is also important. These include knowledge of target cell populations, cell-surface receptors, changes that occur in the target tissue at the molecular and cellular level with progression of the disease, and the mechanism and site of therapeutic action.Keywords: survivin, T34A, apoptosis, proliferation, therap

Concurrent Training

For optimal sports performance, many athletes will require a range of physical qualities including strength, power, and aerobic capacity. Subsequently, training is likely to contain periods where concurrent development of fitness components is required and can typically be classified into two simple training paradigms, endurance and strength training. In order to optimise training, the interaction of these fitness components should be considered as endurance training may interfere with strength training sessions via conflicting molecular signaling which may blunt optimal muscular development. At present, there are a range of conflicting recommendations in the literature, due to the challenges of comparing different training studies and the variables which impact upon the magnitude of adaptation; including volume, intensity (load), rest, sequencing, and concurrent training goals. Most importantly, the overall training stress should be considered to reduce cumulative fatigue and minimise the potential negative effect on strength adaptations via dampened hypertrophic responses. Inter-session rest should be maximized wherever possible to reduce the interaction between competing molecular signaling pathways and provide opportunity to refuel as excesive bouts of training when fuel depleted may restrict subsequent training intensities and blunt any potential adapatations. When training sessions must be completed in close proximity, sequencing should consider the desired training adaptations. If strength adaptations are priority, training sessions should be sequenced, strength-endurance to maximise the strength stimulus. Overall, optimal planning during concurrent training is a complex interaction between a range of variables where strength and conditioning professionals should be conscious of a series of factors and select a training regime that minimises the interference effect within the constraints of their own training logistics

Enhancement of Gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant

Background: Current therapeutic options for advanced pancreatic cancer have been largely disappointing with modest results at best, and though adjuvant therapy remains controversial, most remain in agreement that Gemcitabine should stand as part of any combination study. The inhibitor of apoptosis (IAP) protein Survivin is a key factor in maintaining apoptosis resistance, and its dominant-negative mutant (Survivin-T34A) has been shown to block Survivin, inducing caspase activation and apoptosis. Methods: In this study, exosomes, collected from a melanoma cell line built to harbor a tetracycline-regulated Survivin-T34A, were plated on the pancreatic adenocarcinoma (MIA PaCa-2) cell line. Evaluation of the presence of Survivin-T34A in these exosomes followed by their ability to induce Gemcitabine-potentiative cell killing was the objective of this work. Results: Here we show that exosomes collected in the absence of tetracycline (tet-off) from the engineered melanoma cell do contain Survivin-T34A and when used alone or in combination with Gemcitabine, induced a significant increase in apoptotic cell death when compared to Gemcitabine alone on a variety of pancreatic cancer cell lines. Conclusion: This exosomes/Survivin-T34A study shows that a new delivery method for anticancer proteins within the cancer microenvironment may prove useful in targeting cancers of the pancreas

Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer

Background Survivin is expressed in prostate cancer (PCa), and its downregulation sensitizes PCa cells to chemotherapeutic agents in vitro and in vivo. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose or monitor PCa treatment. Methods Exosomes were purified from the plasma and serum from 39 PCa patients, 20 BPH patients, 8 prostate cancer recurrent and 16 healthy controls using ultracentrifugation and their quantities and qualities were quantified and visualized from both the plasma and the purified exosomes using ELISA and Western blotting, respectively. Results Survivin was significantly increased in the tumor-derived samples, compared to those from BPH and controls with virtually no difference in the quantity of Survivin detected in exosomes collected from newly diagnosed patients exhibiting low (six) or high (nine) Gleason scores. Exosome Survivin levels were also higher in patients that had relapsed on chemotherapy compared to controls. Conclusions These studies demonstrate that Survivin exists in plasma exosomes from both normal, BPH and PCa subjects. The relative amounts of exosomal Survivin in PCa plasma was significantly higher than in those with pre-inflammatory BPH and control plasma. This differential expression of exosomal Survivin was seen with both newly diagnosed and advanced PCa subjects with high or low-grade cancers. Analysis of plasma exosomal Survivin levels may offer a convenient tool for diagnosing or monitoring PCa and may, as it is elevated in low as well as high Gleason scored samples, be used for early detection

Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer

<div><h3>Background</h3><p>Survivin is expressed in prostate cancer (PCa), and its downregulation sensitizes PCa cells to chemotherapeutic agents <em>in vitro</em> and <em>in vivo</em>. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose or monitor PCa treatment.</p> <h3>Methods</h3><p>Exosomes were purified from the plasma and serum from 39 PCa patients, 20 BPH patients, 8 prostate cancer recurrent and 16 healthy controls using ultracentrifugation and their quantities and qualities were quantified and visualized from both the plasma and the purified exosomes using ELISA and Western blotting, respectively.</p> <h3>Results</h3><p>Survivin was significantly increased in the tumor-derived samples, compared to those from BPH and controls with virtually no difference in the quantity of Survivin detected in exosomes collected from newly diagnosed patients exhibiting low (six) or high (nine) Gleason scores. Exosome Survivin levels were also higher in patients that had relapsed on chemotherapy compared to controls.</p> <h3>Conclusions</h3><p>These studies demonstrate that Survivin exists in plasma exosomes from both normal, BPH and PCa subjects. The relative amounts of exosomal Survivin in PCa plasma was significantly higher than in those with pre-inflammatory BPH and control plasma. This differential expression of exosomal Survivin was seen with both newly diagnosed and advanced PCa subjects with high or low-grade cancers. Analysis of plasma exosomal Survivin levels may offer a convenient tool for diagnosing or monitoring PCa and may, as it is elevated in low as well as high Gleason scored samples, be used for early detection.</p> </div

Survivin ELISA and PSA levels of Sera from BPH patients are shown.

<p>Survivin ELISA and PSA levels of Sera from BPH patients are shown.</p