Fitness and health benefits of team handball training for young untrained women-A cross-disciplinary RCT on physiological adaptations and motivational aspects.

PURPOSE: The present study evaluated the effects of regular participation in small-sided team handball training on body composition, osteogenic response, physical performance, and cardiovascular risk factors, as well as well-being and motivation, in young untrained women. METHODS: Twenty-eight untrained 20- to 30-year-old women were randomized to a handball training group (HG; n = 14, height 170 ± 5 cm, weight 73 ± 11 kg, VO2peak 37.7 ± 4.1 mL/min/kg) that trained 1.7 ± 0.3 times per week over 12 weeks (70 min 4 v 4 handball sessions) or an inactive control group (CG; n = 14, 169 ± 5 cm, 71 ± 12 kg, 38.1 ± 3.7 mL/min/kg). Physiological and psychological and motivational training adaptations were assessed pre- and post-intervention by dual-energy X-ray Absorptiometry (DXA) scans, blood sampling, physical tests, and questionnaires. RESULTS: The average heart rate (HR) over all training sessions was equal to 85% ± 6% HRmax. Between-group intervention effects were observed in favor of HG for muscle mass (2.1%, p = 0.024), proximal femur bone mineral density (0.8%, p = 0.041), Yo-Yo IE1 intermittent endurance test level 1 (IE1) performance (35%, p < 0.001), and incremental treadmill test performance (11.5%, p = 0.003), but not total fat mass (p = 0.176), mean arterial blood pressure (p = 0.328), resting HR (p = 0.219), or blood lipids (p = 0.298-0.854). In CG, no changes were observed in any of the measured physiological variables after the training period. Compared to CG, HG had an increase in intrinsic motivation (p < 0.001) and in the well-being subscale "energy" (p = 0.010). CONCLUSION: Participation in regular recreational team handball training organized as small-sided games has marked beneficial effects on physical performance, musculoskeletal fitness, well-being, and motivation in untrained young women.

Cardiac magnetic resonance using late gadolinium enhancement and atrial T1 mapping predicts poor outcome in patients with atrial fibrillation after catheter ablation therapy.

To determine the pre-procedural value of different fibrotic biomarkers and comprehensive cardiac magnetic resonance (CMR) for the prediction of poor response to ablation therapy in patients with atrial fibrillation (AF). Left atrial (LA) late gadolinium enhancement (LGE) and native LA T1 relaxation times were assessed using CMR. Plasma levels of relaxin, myeloperoxidase and serum levels of matrix metalloproteinase (MMP)-mediated cardiac specific titin fragmentation and MMP-mediated type IV collagen degradation were obtained. Poor outcome was defined by the recurrence of AF during 1-year follow-up. 61 patients were included in final analysis. Twenty (32.8%) patients had recurrence of AF. Patients with a recurrence of AF had a higher percentage of LA LGE (26.7 ± 12.5% vs. 17.0 ± 7.7%; P < 0.001), higher LA T1 relaxation times (856.7 ± 112.2 ms vs. 746.8 ± 91.0 ms; P < 0.001) and higher plasma levels of relaxin (0.69 ± 1.34 pg/ml vs. 0.37 ± 0.88 pg/ml; P = 0.035). In the multivariate Cox regression analysis, poor ablation outcome was best predicted by advanced LGE stage (hazard ratio (HR):5.487; P = 0.001) and T1 relaxation times (HR:1.007; P = 0.001). Pre-procedural CMR is a valuable tool for prediction of poor response to catheter ablation therapy in patients with AF. It offers various imaging techniques for outcome prediction and might be valuable for a better patient selection prior to ablation therapy.

Serum type XVI collagen is associated with colorectal cancer and ulcerative colitis indicating a pathological role in gastrointestinal disorders.

Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have biomarker potential in GI disorders such as colorectal cancer (CRC) and ulcerative colitis (UC). The aim of this study was to determine whether col-16 can serve as a biomarker for altered ECM remodeling in patients with CRC and UC. A monoclonal antibody was raised against the C-terminal end of col-16 (PRO-C16), and a competitive enzyme-linked immunosorbent assay (ELISA) was developed and technically validated. Levels of PRO-C16 were measured in serum from patients with CRC (before (n = 50) and 3 months after (n = 23) tumor resections), UC (n = 39) and healthy controls (n = 50). The PRO-C16 ELISA was specific toward the C-terminal of col-16. PRO-C16 was significantly elevated both in serum from patients with CRC (P = 0.0026) and UC (P < 0.0001) compared to controls. No difference was detected in levels of PRO-C16 between patients with CRC at baseline and 3 months after tumor resections (P > 0.999). Levels of PRO-C16 identified patients with a GI disorder with a positive predictive value of 0.9 and an odds ratio of 12 (95%CI = 4.5-29.5, P < 0.0001). The newly developed assay detected significantly elevated levels of PRO-C16 in serum from patients with GI disorders compared to controls suggesting its potential as a biomarker in this setting. Future studies are needed to validate these findings.

Higher Collagen VI Formation Is Associated With All-Cause Mortality in Patients With Type 2 Diabetes and Microalbuminuria.

OBJECTIVE: Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI formation, is prognostic for adverse outcomes in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS: In a prospective, observational study, we measured PRO-C6 in the serum (S-PRO-C6) and urine (U-PRO-C6) of 198 patients with type 2 diabetes and microalbuminuria without symptoms of coronary artery disease. Patients were followed for a median of 6.5 years, and end points were a composite of cardiovascular events (n = 38), all-cause mortality (n = 26), and reduction of estimated glomerular filtration rate (eGFR) of >30% (disease progression [n = 42]). Cox models were unadjusted and adjusted for the conventional risk factors of sex, age, BMI, systolic blood pressure, LDL cholesterol, smoking, HbA1c, plasma creatinine, and urinary albumin excretion rate. RESULTS: Doubling of S-PRO-C6 increased hazards for cardiovascular events (hazard ratio 3.06 [95% CI 1.31-7.14]), all-cause mortality (6.91 [2.96-16.11]), and disease progression (4.81 [1.92-12.01]). Addition of S-PRO-C6 to a model containing conventional risk factors improved relative integrated discrimination by 22.5% for cardiovascular events (P = 0.02), 76.8% for all-cause mortality (P = 0.002), and 53.3% for disease progression (P = 0.004). U-PRO-C6 was not significantly associated with any of the outcomes. CONCLUSIONS: S-PRO-C6 generated during COL VI formation predicts cardiovascular events, all-cause mortality, and disease progression in patients with type 2 diabetes and microalbuminuria.

Particle release and control of worker exposure during laboratory-scale synthesis, handling and simulated spills of manufactured nanomaterials in fume hoods.

Fume hoods are one of the most common types of equipment applied to reduce the potential of particle exposure in laboratory environments. A number of previous studies have shown particle release during work with nanomaterials under fume hoods. Here, we assessed laboratory workers' inhalation exposure during synthesis and handling of CuO, TiO2 and ZnO in a fume hood. In addition, we tested the capacity of a fume hood to prevent particle release to laboratory air during simulated spillage of different powders (silica fume, zirconia TZ-3Y and TiO2). Airborne particle concentrations were measured in near field, far field, and in the breathing zone of the worker. Handling CuO nanoparticles increased the concentration of small particles (< 58 nm) inside the fume hood (up to 1 × 105 cm-3). Synthesis, handling and packaging of ZnO and TiO2 nanoparticles did not result in detectable particle release to the laboratory air. Simulated powder spills showed a systematic increase in the particle concentrations inside the fume hood with increasing amount of material and drop height. Despite powder spills were sometimes observed to eject into the laboratory room, the spill events were rarely associated with notable release of particles from the fume hood. Overall, this study shows that a fume hood generally offers sufficient exposure control during synthesis and handling of nanomaterials. An appropriate fume hood with adequate sash height and face velocity prevents 98.3% of particles release into the surrounding environment. Care should still be made to consider spills and high cleanliness to prevent exposure via resuspension and inadvertent exposure by secondary routes.

Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy.

Aim Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patients with diffuse myocardial fibrosis from asymptomatic controls. Methods and results Seventy-one women with angina pectoris without significant coronary artery disease assessed by invasive coronary angiogram were included. Competitive enzyme-linked immunosorbent assays (ELISAs) measuring circulating protein fragments in serum assessed the formation and degradation of collagen type III (Pro-C3, C3M and C3C), IV (P4NP7S and C4M), V (Pro-C5 and C5M) and VI (Pro-C6 and C6M), and degradation of collagen type I (C1M). Serum samples from 32 age-matched asymptomatic women were included as controls. Symptomatic women presented significantly elevated levels of Pro-C6, C3C, C3M, C4M and C8-C ( p < 0.0001-0.0058) and significantly decreased levels of Pro-C3, C5M and C6M ( p < 0.0001-0.041), reflecting accelerated collagen turnover and an imbalanced collagen formation and degradation compared to controls. Cardiac magnetic resonance T1 mapping was performed to determine extracellular volume fraction and thus diffuse myocardial fibrosis. A significant association was identified between C5M and extracellular volume fraction by cardiac magnetic resonance ( p = 0.01). Conclusion Women with angina pectoris, but without significant obstructive coronary artery disease, showed an imbalanced collagen turnover compared to asymptomatic controls. The examined biomarkers are tools to monitor active collagen remodelling in patients with angina pectoris, in risk of developing myocardial fibrosis.

Precision-Cut Kidney Slices as a Tool to Understand the Dynamics of Extracellular Matrix Remodeling in Renal Fibrosis.

The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) surgery of the right ureter. The left kidney (contralateral) was used as internal control. Six rats were sham operated and used as the control group. Rats were terminated two weeks after the surgery; the kidneys were excised and precision-cut kidney slices (PCKSs) were cultured for five days in serum-free medium. Markers of collagen type I formation (P1NP), collagen type I and III degradation (C1M and C3M), and α-smooth muscle actin (αSMA) were measured in the PCKS supernatants by enzyme-linked immunosorbent assay. P1NP, C1M, C3M, and α-SMA were increased up to 2- to 13-fold in supernatants of tissue slices from the UUO-ligated kidneys compared with the contralateral kidneys (P < 0.001) and with the kidneys of sham-operated animals (P < 0.0001). The markers could also reflect the level of fibrosis in different animals. The UUO PCKS ex vivo model provides a valuable translational tool for investigating the extracellular matrix remodeling associated with renal interstitial fibrosis.

Serum and urine markers of collagen degradation reflect renal fibrosis in experimental kidney diseases.

BACKGROUND: The extent of renal fibrosis in chronic kidney disease (CKD) is the best predictor for progression of most renal diseases. To date, no established biomarkers of renal fibrosis exist. METHODS: We measured circulating and urinary-specific matrix metalloproteinase (MMP)-generated collagen type I and III degradation fragments (C1M and C3M) and an N-terminal propeptide of collagen III (Pro-C3), as markers of collagen type III production, in three rat models of CKD and fibrosis: renal mass reduction (5/6 nephrectomy), progressive glomerulonephritis (chronic anti-Thy1.1 nephritis) and adenine crystal-induced nephropathy. Healthy rats served as controls. RESULTS: In all three models, the animals developed significant CKD and renal fibrosis. Compared with healthy rats, serum C1M and C3M significantly increased in rats with 5/6 nephrectomy and adenine nephropathy (2- to 3-fold), but not with chronic anti-Thy1.1 nephritis. Urinary C1M and C3M levels increased 9- to 100-fold in all three models compared with controls. Urinary degradation markers correlated closely with renal deposition of collagen type I and type III. Pro-C3 was significantly increased only in the urine of 5/6 nephrectomy rats. CONCLUSIONS: In particular, urinary markers of MMP-driven collagen degradation, rather than collagen production markers, may represent a novel, specific and non-invasive diagnostic approach to assess kidney fibrosis.