Progressive Resistance Training and Cancer Testis (PROTRACT) - Efficacy of resistance training on muscle function, morphology and inflammatory profile in testicular cancer patients undergoing chemotherapy: design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Standard treatment for patients with disseminated germ cell tumors is combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This treatment is highly effective, but the majority of patients experience severe adverse effects during treatment and are at risk of developing considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, and pulmonary toxicity. One neglected side effect is the significant muscular fatigue mentioned by many patients with testicular cancer both during and after treatment. Very limited information exists concerning the patho-physiological effects of antineoplastic agents on skeletal muscle. The primary aim of this study is to investigate the effects of BEP-treatment on the skeletal musculature in testicular cancer patients, and to examine whether the expected treatment-induced muscular deterioration can be attenuated or even reversed by high intensity progressive resistance training (HIPRT).</p> <p>Design/Methods</p> <p>The PROTRACT study is a randomized controlled trial in 30 testicular cancer patients undergoing three cycles of BEP chemotherapy. Participants will be randomized to either a 9-week HIPRT program (STR) initiated at the onset of treatment, or to standard care (UNT). 15 healthy matched control subjects (CON) will complete the same HIPRT program. All participants will take part in 3 assessment rounds (baseline, 9 wks, 21 wks) including muscle biopsies, maximum muscle strength tests, whole body DXA scan and blood samples. <it>Primary outcome</it>: mean fiber area and fiber type composition measured by histochemical analyses, satellite cells and levels of protein and mRNA expression of intracellular mediators of protein turnover. Secondary outcomes: maximum muscle strength and muscle power measured by maximum voluntary contraction and leg-extensor-power tests, body composition assessed by DXA scan, and systemic inflammation analyzed by circulating inflammatory markers, lipid and glucose metabolism in blood samples. Health related Quality of Life (QoL) will be assessed by validated questionnaires (EORTC QLQ-C30, SF-36).</p> <p>Discussion</p> <p>This study investigates the muscular effects of antineoplastic agents in testicular cancer patients, and furthermore evaluates whether HIPRT has a positive influence on side effects related to chemotherapy. A more extensive knowledge of the interaction between cytotoxic-induced physiological impairment and exercise-induced improvement is imperative for the future development of optimal rehabilitation programs for cancer patients.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN32132990">ISRCTN32132990</a>.</p

Scalable Group Level Probabilistic Sparse Factor Analysis

Many data-driven approaches exist to extract neural representations of functional magnetic resonance imaging (fMRI) data, but most of them lack a proper probabilistic formulation. We propose a group level scalable probabilistic sparse factor analysis (psFA) allowing spatially sparse maps, component pruning using automatic relevance determination (ARD) and subject specific heteroscedastic spatial noise modeling. For task-based and resting state fMRI, we show that the sparsity constraint gives rise to components similar to those obtained by group independent component analysis. The noise modeling shows that noise is reduced in areas typically associated with activation by the experimental design. The psFA model identifies sparse components and the probabilistic setting provides a natural way to handle parameter uncertainties. The variational Bayesian framework easily extends to more complex noise models than the presently considered.Comment: 10 pages plus 5 pages appendix, Submitted to ICASSP 1

Itch sensitization?:A systematic review of studies using quantitative sensory testing in patients with chronic itch

As well established for patients with chronic pain, patients suffering from chronic itch also exhibit signs of peripheral and central sensitization. This has been linked to parallel neuroplastic sensitization processes. However, for chronic itch, sensitization has not yet been systematically assessed, studied, and hence validated. This review (Prospero CRD42016043002) summarizes and meta-analytically evaluates whether sensory aberrations including sensitization for itch occur in chronic itch. Databases PubMed, Embase, and Cochrane Library were searched for studies investigating somatosensory sensitivity assessment by quantitative sensory testing stimuli, including experimental cutaneous chemical pruritic provocations, in patients with chronic itch from skin/neurological conditions and compared with healthy controls. Outcomes were extracted for lesional and nonlesional skin, and risk of biases were assessed. Meta-analyses were performed when sufficient quantitative data were available. Of 4667 identified articles, 46 were included and 25 were eligible for meta-analyses. Patients (66% atopic dermatitis [AD]) were found more sensitive than the controls to histamine-evoked itch in lesional skin (standardized mean difference [SMD]: 0.66 confidence interval [CI]: 0.16-1.15), but not nonlesionally (SMD: −0.26 [CI: −0.58 to 0.06]). Cowhage did not evoke more itch in nonlesional skin of patients as compared to the controls (SMD: 0.38 [CI: −0.04 to 0.81]). For numerous other chemical provocations as well as for mechanical, thermal, and electrical stimulation paradigms, results were ambiguous or based on few studies. Patients with chronic itch are only robustly sensitized to various chemical pruritic stimuli when applied lesionally. More studies on somatosensory aberrations in chronic itch conditions other than AD are needed to establish whether sensitization is robustly present across chronic itch conditions.Health and self-regulatio

The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality

ABSTRACTThis multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were increased significantly (median 5.5; range 2.4–21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5–4.0 ng/mL, p 0.001). Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors (n = 117; p < 0.001). No correlation was found between suPAR levels and C-reactive protein. In univariate logistic regression analysis, hypotension, renal failure, cerebral symptoms and high serum concentrations of protein YKL-40 and suPAR were associated significantly with mortality (p < 0.05). In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1–158). The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis. This plasma protein may be used to identify patients who are severely ill with pneumococcal bacteraemia

Diffusion, Fragmentation and Coagulation Processes: Analytical and Numerical Results

We formulate dynamical rate equations for physical processes driven by a combination of diffusive growth, size fragmentation and fragment coagulation. Initially, we consider processes where coagulation is absent. In this case we solve the rate equation exactly leading to size distributions of Bessel type which fall off as $\exp(-x^{3/2})$ for large $x$-values. Moreover, we provide explicit formulas for the expansion coefficients in terms of Airy functions. Introducing the coagulation term, the full non-linear model is mapped exactly onto a Riccati equation that enables us to derive various asymptotic solutions for the distribution function. In particular, we find a standard exponential decay, $\exp(-x)$, for large $x$, and observe a crossover from the Bessel function for intermediate values of $x$. These findings are checked by numerical simulations and we find perfect agreement between the theoretical predictions and numerical results.Comment: (28 pages, 6 figures, v2+v3 minor corrections