Unchanged content of oxidative enzymes in fast-twitch muscle fibers and V˙O2 kinetics after intensified training in trained cyclists.

PublishedJournal ArticleThe present study examined if high intensity training (HIT) could increase the expression of oxidative enzymes in fast-twitch muscle fibers causing a faster oxygen uptake (V˙O2) response during intense (INT), but not moderate (MOD), exercise and reduce the V˙O2 slow component and muscle metabolic perturbation during INT. Pulmonary V˙O2 kinetics was determined in eight trained male cyclists (V˙O2-max: 59 ± 4 (means ± SD) mL min(-1) kg(-1)) during MOD (205 ± 12 W ~65% V˙O2-max) and INT (286 ± 17 W ~85% V˙O2-max) exercise before and after a 7-week HIT period (30-sec sprints and 4-min intervals) with a 50% reduction in volume. Both before and after HIT the content in fast-twitch fibers of CS (P < 0.05) and COX-4 (P < 0.01) was lower, whereas PFK was higher (P < 0.001) than in slow-twitch fibers. Content of CS, COX-4, and PFK in homogenate and fast-twitch fibers was unchanged with HIT. Maximal activity (μmol g DW(-1) min(-1)) of CS (56 ± 8 post-HIT vs. 59 ± 10 pre-HIT), HAD (27 ± 6 vs. 29 ± 3) and PFK (340 ± 69 vs. 318 ± 105) and the capillary to fiber ratio (2.30 ± 0.16 vs. 2.38 ± 0.20) was unaltered following HIT. V˙O2 kinetics was unchanged with HIT and the speed of the primary response did not differ between MOD and INT. Muscle creatine phosphate was lower (42 ± 15 vs. 66 ± 17 mmol kg DW(-1)) and muscle lactate was higher (40 ± 18 vs. 14 ± 5 mmol kg DW(-1)) at 6 min of INT (P < 0.05) after compared to before HIT. A period of intensified training with a volume reduction did not increase the content of oxidative enzymes in fast-twitch fibers, and did not change V˙O2 kinetics.The study was supported by Team Danmark (Danish Elite Sport Organization)

The Maltase Involved in Starch Metabolism in Barley Endosperm Is Encoded by a Single Gene

During germination and early seedling growth of barley (Hordeum vulgare), maltase is responsible for the conversion of maltose produced by starch degradation in the endosperm to glucose for seedling growth. Despite the potential relevance of this enzyme for malting and the production of alcoholic beverages, neither the nature nor the role of maltase is fully understood. Although only one gene encoding maltase has been identified with certainty, there is evidence for the existence of other genes and for multiple forms of the enzyme. It has been proposed that maltase may be involved directly in starch granule degradation as well as in maltose hydrolysis. The aim of our work was to discover the nature of maltase in barley endosperm. We used ion exchange chromatography to fractionate maltase activity from endosperm of young seedlings, and we partially purified activity for protein identification. We compared maltase activity in wild-type barley and transgenic lines with reduced expression of the previously-characterised maltase gene Agl97, and we used genomic and transcriptomic information to search for further maltase genes. We show that all of the maltase activity in the barley endosperm can be accounted for by a single gene, Agl97. Multiple forms of the enzyme most likely arise from proteolysis and other post-translational modifications

Skeletal muscle and performance adaptations to high-intensity training in elite male soccer players: speed endurance runs versus small-sided game training.

PURPOSE: To examine the skeletal muscle and performance responses across two different exercise training modalities which are highly applied in soccer training. METHODS: Using an RCT design, 39 well-trained male soccer players were randomized into either a speed endurance training (SET; n = 21) or a small-sided game group (SSG; n = 18). Over 4 weeks, thrice weekly, SET performed 6-10 × 30-s all-out runs with 3-min recovery, while SSG completed 2 × 7-9-min small-sided games with 2-min recovery. Muscle biopsies were obtained from m. vastus lateralis pre and post intervention and were subsequently analysed for metabolic enzyme activity and muscle protein expression. Moreover, the Yo-Yo Intermittent Recovery level 2 test (Yo-Yo IR2) was performed. RESULTS: Muscle CS maximal activity increased (P < 0.05) by 18% in SET only, demonstrating larger (P < 0.05) improvement than SSG, while HAD activity increased (P < 0.05) by 24% in both groups. Na(+)-K(+) ATPase α1 subunit protein expression increased (P < 0.05) in SET and SSG (19 and 37%, respectively), while MCT4 protein expression rose (P < 0.05) by 30 and 61% in SET and SSG, respectively. SOD2 protein expression increased (P < 0.05) by 28 and 37% in SET and SSG, respectively, while GLUT-4 protein expression increased (P < 0.05) by 40% in SSG only. Finally, SET displayed 39% greater improvement (P < 0.05) in Yo-Yo IR2 performance than SSG. CONCLUSION: Speed endurance training improved muscle oxidative capacity and exercise performance more pronouncedly than small-sided game training, but comparable responses were in muscle ion transporters and antioxidative capacity in well-trained male soccer players

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Neutrinos

229 pages229 pages229 pagesThe Proceedings of the 2011 workshop on Fundamental Physics at the Intensity Frontier. Science opportunities at the intensity frontier are identified and described in the areas of heavy quarks, charged leptons, neutrinos, proton decay, new light weakly-coupled particles, and nucleons, nuclei, and atoms

Does long-term care use within primary health care reduce hospital use among older people in Norway? A national five-year population-based observational study

<p>Abstract</p> <p>Background</p> <p>Population ageing may threaten the sustainability of future health care systems. Strengthening primary health care, including long-term care, is one of several measures being taken to handle future health care needs and budgets. There is limited and inconsistent evidence on the effect of long-term care on hospital use. We explored the relationship between the total use of long-term care within public primary health care in Norway and the use of hospital beds when adjusting for various effect modifiers and confounders.</p> <p>Methods</p> <p>This national population-based observational study consists of all Norwegians (59% women) older than 66 years (N = 605676) (13.2% of total population) in 2002-2006. The unit of analysis was defined by municipality, age and sex. The association between total number of recipients of long-term care per 1000 inhabitants (LTC-rate) and hospital days per 1000 inhabitants (HD-rate) was analysed in a linear regression model. Modifying and confounding effects of socioeconomic, demographic and geographic variables were included in the final model. We defined a difference in hospitalization rates of more than 1000 days per 1000 inhabitants as clinically important.</p> <p>Results</p> <p>Thirty-one percent of women and eighteen percent of men were long-term care users. Men had higher HD-rates than women. The crude association between LTC-rate and HD-rate was weakly negative. We identified two effect modifiers (age and sex) and two strong confounders (travel time to hospital and mortality). Age and sex stratification and adjustments for confounders revealed a positive statistically significant but not clinically important relationship between LTC-rates and hospitalization for women aged 67-79 years and all men. For women 80 years and over there was a weak but negative relationship which was neither statistically significant nor clinically important.</p> <p>Conclusions</p> <p>We found a weak positive adjusted association between LTC-rates and HD-rates. Opposite to common belief, we found that increased volume of LTC by itself did not reduce pressure on hospitals. There still is a need to study integrated care models for the elderly in the Norwegian setting and to explore further why municipalities far away from hospital achieve lower use of hospital beds.</p

Are waiting times for hospital admissions affected by patients' choices and mobility?

Background Waiting times for elective care have been considered a serious problem in many health care systems. A topic of particular concern has been how administrative boundaries act as barriers to efficient patient flows. In Norway, a policy combining patient's choice of hospital and removal of restriction on referrals was introduced in 2001, thereby creating a nationwide competitive referral system for elective hospital treatment. The article aims to analyse if patient choice and an increased opportunity for geographical mobility has reduced waiting times for individual elective patients. Methods A survey conducted among Norwegian somatic patients in 2004 gave information about whether the choice of hospital was made by the individual patient or by others. Survey data was then merged with administrative data on which hospital that actually performed the treatment. The administrative data also gave individual waiting time for hospital admission. Demographics, socio-economic position, and medical need were controlled for to determine the effect of choice and mobility upon waiting time. Several statistical models, including one with instrument variables for choice and mobility, were run. Results Patients who had neither chosen hospital individually nor bypassed the local hospital for other reasons faced the longest waiting times. Next were patients who individually had chosen the local hospital, followed by patients who had not made an individual choice, but had bypassed the local hospital for other reasons. Patients who had made a choice to bypass the local hospitals waited on average 11 weeks less than the first group. Conclusion The analysis indicates that a policy combining increased opportunity for hospital choice with the removal of rules restricting referrals can reduce waiting times for individual elective patients. Results were robust over different model specifications

GLUT4 and UBC9 Protein Expression Is Reduced in Muscle from Type 2 Diabetic Patients with Severe Insulin Resistance

Subgroups of patients with type 2 diabetes mellitus demand large insulin doses to maintain euglycemia. These patients are characterized by severe skeletal muscle insulin resistance and the underlying pathology remains unclear. The purpose of this study was to examine protein expression of the principal glucose transporter, GLUT4, and associated proteins in skeletal muscle from type 2 diabetic patients characterized by severe insulin resistance.Seven type 2 diabetic patients with severe insulin resistance (mean insulin dose 195 IU/day) were compared with seven age matched type 2 diabetic patients who did not require insulin treatment, and with an age matched healthy control group. Protein expression of GLUT4 and associated proteins was assessed in muscle and fat biopsies using standard western blotting techniques.GLUT4 protein expression was significantly reduced by ∼30 pct in skeletal muscle tissue from severely insulin resistant type 2 diabetic subjects, compared with both healthy controls and type 2 diabetic subjects that did not require insulin treatment. In fat tissue, GLUT4 protein expression was reduced in both diabetic groups. In skeletal muscle, the reduced GLUT4 expression in severe insulin resistance was associated with decreased ubiquitin-conjugating enzyme 9 (UBC9) expression while expression of GLUT1, TBC1D1 and AS160 was not significantly different among type 2 diabetic patients and matched controls.Type 2 diabetic patients with severe insulin resistance have reduced expression of GLUT4 in skeletal muscle compared to patients treated with oral antidiabetic drugs alone. GLUT4 protein levels may therefore play a role in the pathology behind type 2 diabetes mellitus among subgroups of patients, and this may explain the heterogeneous response to insulin treatment. This new finding contributes to the understanding of the underlying mechanisms for the development of extreme insulin resistance

Environmental and Lifestyle Factors Associated with Perceived Facial Age in Chinese Women

Perceived facial age has been proposed as a biomarker of ageing with ‘looking young for one’s age' linked to physical and cognitive functioning and to increased survival for Caucasians. We have investigated the environmental and lifestyle factors associated with perceived facial ageing in Chinese women. Facial photographs were collected from 250 Chinese women, aged 25–70 years in Shanghai, China. Perceived facial age was determined and related to chronological age for each participant. Lifestyle and health information was collected by questionnaire. Bivariate analyses (controlling for chronological age) identified and quantified lifestyle variables associated with perceived facial age. Independent predictors of perceived age were identified by multivariate modelling. Factors which significantly associated with looking younger for one's chronological age included greater years of education (p<0.001), fewer household members (p = 0.027), menopausal status (p = 0.020), frequency of visiting one's doctor (p = 0.013), working indoors (p<0.001), spending less time in the sun (p = 0.015), moderate levels of physical activity (p = 0.004), higher frequency of teeth cleaning (p<0.001) and more frequent use of facial care products: cleanser (p<0.001); moisturiser (p = 0.016) or night cream (p = 0.016). Overall, 36.5% of the variation in the difference between perceived and chronological age could be explained by a combination of chronological age and 6 independent lifestyle variables. We have thus identified and quantified a number of factors associated with younger appearance in Chinese women. Presentation of these factors in the context of facial appearance could provide significant motivation for the adoption of a range of healthy behaviours at the level of both individuals and populations