Gender-specific usage of intramyocellular lipids and glycogen during exercise

PURPOSE: Gender-specific differences in substrate utilization during exercise have been reported, typically such that women rely more on fat than men. This study investigated whether gender differences exist in the utilization of intramyocellular lipids (IMCL) and glycogen. METHODS: IMCL and glycogen, as well as total fat and carbohydrate (CHO) oxidation were measured in nine males and nine females before, during, and after an endurance exercise. The trained subjects exercised on a bicycle ergometer at 50% maximal workload for 3 h. IMCL and glycogen were determined in the thigh by magnetic resonance spectroscopy. Oxygen uptake (VO(2)) and carbon dioxide production were determined by open circuit spirometry to calculate total fat and CHO oxidation. Relative power output, percent of maximum heart rate, VO(2peak), and respiratory exchange ratio were the same. RESULTS: Average fat oxidation was the same, whereas CHO oxidation was significantly higher in males compared with females. The relative contribution of these fuels to total energy used were similar in males and females. Males and females depleted IMCL and glycogen significantly (P < 0.001) during the 3-h exercise. IMCL levels at rest (P < 0.05) and its depletion during exercise (P < 0.001) were significantly higher in males compared with females, whereas glycogen was stored and used in the same range by both genders. CONCLUSION: During this 3-h exercise, energy supplies from fat and CHO were similar in both genders, and males as well as females reduced their IMCL stores significantly. The larger contribution of IMCL during exercise in males compared with females could either be a result of gender-specific substrate selection, or different long-term training habit.

Benzo1,2-b:4,5-b 'difuran-based sensitizers for dye-sensitized solar cells

Two BDF-based organic sensitizers, as first examples for their use in dye-sensitized solar cells, are prepared and characterized. They yield promising power conversion efficiencies of up to 5.5 and high open circuit voltages up to 0.82 V. This work demonstrates that the BDF chromophore acts as an effective donor in organic sensitizers.

Potential influence of the anesthetic technique used during open radical prostatectomy on prostate cancer-related outcome: a retrospective study

Recently published studies suggest that the anesthetic technique used during oncologic surgery affects cancer recurrence. To evaluate the effect of anesthetic technique on disease progression and long-term survival, we compared patients receiving general anesthesia plus intraoperative and postoperative thoracic epidural analgesia with patients receiving general anesthesia alone undergoing open retropubic radical prostatectomy with extended pelvic lymph node dissection.

Self-sufficient control of urate homeostasis in mice by a synthetic circuit

Synthetic biology has shown that the metabolic behavior of mammalian cells can be altered by genetic devices such as epigenetic and hysteretic switches, timers and oscillators, biocomputers, hormone systems and heterologous metabolic shunts. To explore the potential of such devices for therapeutic strategies, we designed a synthetic mammalian circuit to maintain uric acid homeostasis in the bloodstream, disturbance of which is associated with tumor lysis syndrome and gout. This synthetic device consists of a modified Deinococcus radiodurans-derived protein that senses uric acids levels and triggers dose-dependent derepression of a secretion-engineered Aspergillus flavus urate oxidase that eliminates uric acid. In urate oxidase-deficient mice, which develop acute hyperuricemia, the synthetic circuit decreased blood urate concentration to stable sub-pathologic levels in a dose-dependent manner and reduced uric acid crystal deposits in the kidney. Synthetic gene-network devices providing self-sufficient control of pathologic metabolites represent molecular prostheses, which may foster advances in future gene- and cell-based therapies.

Intrahepatic gas at postmortem computed tomography: forensic experience as a potential guide for in vivo trauma imaging

BACKGROUND: Until August 2004 there were 106 forensic cases examined with postmortem multislice computed tomography (MSCT) and magnetic resonance (MR) imaging before traditional autopsy within the Virtopsy project. Intrahepatic gas (IHG) was a frequent finding in postmortem MSCT examinations. The aim of this study was to investigate its cause and significance. METHODS: There were 84 virtopsy cases retrospectively investigated concerning the occurrence, location, and volume of IHG in postmortem MSCT imaging (1.25 mm collimation, 1.25 mm thickness). We assessed and noted the occurrence of intestinal distention, putrefaction, and systemic gas embolisms and the cause of death, possible open trauma, possible artificial respiration, and the postmortem interval. We investigated the relations between the findings using the contingency table (chi2 test) and the comparison of the postmortem intervals in both groups was performed using the t test in 79 nonputrefied corpses. RESULTS: IHG was found in 47 cases (59.5%). In five of the cases, the IHG was caused or influenced by putrefaction. Gas distribution within the liver of the remaining 42 cases was as follows: hepatic arteries in 21 cases, hepatic veins in 35 cases, and portal vein branches in 13 cases; among which combinations also occurred in 20 cases. The presence of IHG was strongly related to open trauma with systemic gas. Pulmonary barotrauma as occurring under artificial respiration or in drowning also caused IHG. Putrefaction did not seem to influence the occurrence of IHG until macroscopic signs of putrefaction were noticeable. CONCLUSIONS: IHG is a frequent finding in traumatic causes of death and requires a systemic gas embolism. Exceptions are putrefied or burned corpses. Common clinical causes such as necrotic bowel diseases appear rarely as a cause of IHG in our forensic case material.

Potential of information technology in dental education

The use of information technology (IT) in dentistry is far ranging. In order to produce a working document for the dental educator, this paper focuses on those methods where IT can assist in the education and competence development of dental students and dentists (e.g. e-learning, distance learning, simulations and computer-based assessment). Web pages and other information-gathering devices have become an essential part of our daily life, as they provide extensive information on all aspects of our society. This is mirrored in dental education where there are many different tools available, as listed in this report. IT offers added value to traditional teaching methods and examples are provided. In spite of the continuing debate on the learning effectiveness of e-learning applications, students request such approaches as an adjunct to the traditional delivery of learning materials. Faculty require support to enable them to effectively use the technology to the benefit of their students. This support should be provided by the institution and it is suggested that, where possible, institutions should appoint an e-learning champion with good interpersonal skills to support and encourage faculty change. From a global prospective, all students and faculty should have access to e-learning tools. This report encourages open access to e-learning material, platforms and programs. The quality of such learning materials must have well defined learning objectives and involve peer review to ensure content validity, accuracy, currency, the use of evidence-based data and the use of best practices. To ensure that the developers' intellectual rights are protected, the original content needs to be secure from unauthorized changes. Strategies and recommendations on how to improve the quality of e-learning are outlined. In the area of assessment, traditional examination schemes can be enriched by IT, whilst the Internet can provide many innovative approaches. Future trends in IT will evolve around improved uptake and access facilitated by the technology (hardware and software). The use of Web 2.0 shows considerable promise and this may have implications on a global level. For example, the one-laptop-per-child project is the best example of what Web 2.0 can do: minimal use of hardware to maximize use of the Internet structure. In essence, simple technology can overcome many of the barriers to learning. IT will always remain exciting, as it is always changing and the users, whether dental students, educators or patients are like chameleons adapting to the ever-changing landscape.

From Complex to Stochastic Potential: Heavy Quarkonia in the Quark-Gluon Plasma

The in-medium physics of heavy quarkonium is an ideal proving ground for our ability to connect knowledge about the fundamental laws of physics to phenomenological predictions. One possible route to take is to attempt a description of heavy quark bound states at finite temperature through a Schrödinger equation with an instantaneous potential. Here we review recent progress in devising a comprehensive approach to define such a potential from first principles QCD and extract its, in general complex, values from non-perturbative lattice QCD simulations. Based on the theory of open quantum systems we will show how to interpret the role of the imaginary part in terms of spatial decoherence by introducing the concept of a stochastic potential. Shortcomings as well as possible paths for improvement are discussed.

Improvement of cardiac function with device-based diaphragmatic stimulation in chronic heart failure patients: the randomized, open-label, crossover Epiphrenic II Pilot Trial.

AIMS Device-based pacing-induced diaphragmatic stimulation (PIDS) may have therapeutic potential for chronic heart failure (HF) patients. We studied the effects of PIDS on cardiac function and functional outcomes. METHODS AND RESULTS In 24 chronic HF patients with CRT, an additional electrode was attached to the left diaphragm. Randomized into two groups, patients received the following PIDS modes for 3 weeks in a different sequence: (i) PIDS off (control group); (ii) PIDS 0 ms mode (PIDS simultaneously with ventricular CRT pulse); or (iii) PIDS optimized mode (PIDS with optimized delay to ventricular CRT pulse). For PIDS optimization, acoustic cardiography was used. Effects of each PIDS mode on dyspnoea, power during exercise testing, and LVEF were assessed. Dyspnoea improved with the PIDS 0 ms mode (P = 0.057) and the PIDS optimized mode (P = 0.034) as compared with the control group. Maximal power increased from median 100.5 W in the control group to 104.0 W in the PIDS 0 ms mode (P = 0.092) and 109.5 W in the PIDS optimized mode (P = 0.022). Median LVEF was 33.5% in the control group, 33.0% in the PIDS 0 ms mode, and 37.0% in the PIDS optimized mode (P = 0.763 and P = 0.009 as compared with the control group, respectively). PIDS was asymptomatic in all patients. CONCLUSION PIDS improves dyspnoea, working capacity, and LVEF in chronic HF patients over a 3 week period in addition to CRT. This pilot study demonstrates proof of principle of an innovative technology which should be confirmed in a larger sample. TRIAL REGISTRATION NCT00769678.

Novel radiotherapy techniques for involved-field and involved-node treatment of mediastinal Hodgkin lymphoma: when should they be considered and which questions remain open?

PURPOSE Hodgkin lymphoma (HL) is a highly curable disease. Reducing late complications and second malignancies has become increasingly important. Radiotherapy target paradigms are currently changing and radiotherapy techniques are evolving rapidly. DESIGN This overview reports to what extent target volume reduction in involved-node (IN) and advanced radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT) and proton therapy-compared with involved-field (IF) and 3D radiotherapy (3D-RT)- can reduce high doses to organs at risk (OAR) and examines the issues that still remain open. RESULTS Although no comparison of all available techniques on identical patient datasets exists, clear patterns emerge. Advanced dose-calculation algorithms (e.g., convolution-superposition/Monte Carlo) should be used in mediastinal HL. INRT consistently reduces treated volumes when compared with IFRT with the exact amount depending on the INRT definition. The number of patients that might significantly benefit from highly conformal techniques such as IMRT over 3D-RT regarding high-dose exposure to organs at risk (OAR) is smaller with INRT. The impact of larger volumes treated with low doses in advanced techniques is unclear. The type of IMRT used (static/rotational) is of minor importance. All advanced photon techniques result in similar potential benefits and disadvantages, therefore only the degree-of-modulation should be chosen based on individual treatment goals. Treatment in deep inspiration breath hold is being evaluated. Protons theoretically provide both excellent high-dose conformality and reduced integral dose. CONCLUSION Further reduction of treated volumes most effectively reduces OAR dose, most likely without disadvantages if the excellent control rates achieved currently are maintained. For both IFRT and INRT, the benefits of advanced radiotherapy techniques depend on the individual patient/target geometry. Their use should therefore be decided case by case with comparative treatment planning.

Open issues in transcatheter aortic valve implantation. Part 2: procedural issues and outcomes after transcatheter aortic valve implantation.

This article provides an overview on procedure-related issues and uncertainties in outcomes after transcatheter aortic valve implantation (TAVI). The different access sites and how to select them in an individual patient are discussed. Also, the occurrence and potential predictors of aortic regurgitation (AR) after TAVI are addressed. The different methods to quantify AR are reviewed, and it appears that accurate and reproducible quantification is suboptimal. Complications such as prosthesis-patient mismatch and conduction abnormalities (and need for permanent pacemaker) are discussed, as well as cerebrovascular events, which emphasize the development of optimal anti-coagulative strategies. Finally, recent registries have shown the adoption of TAVI in the real world, but longer follow-up studies are needed to evaluate the outcome (but also prosthesis durability). Additionally, future studies are briefly discussed, which will address the use of TAVI in pure AR and lower-risk patients.

Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial

BACKGROUND Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder. METHODS This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756. FINDINGS From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7·0 years (IQR 5·2-8·7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0·78, 95% CI 0·56-1·08; p=0·13). Immediate treatment significantly prolonged progression-free survival compared with deferred treatment (HR 0·54, 95% CI 0·4-0·73, p<0·0001), with 5-year progression-free survival of 47·6% (95% CI 38·8-55·9) in the immediate treatment group and 31·8% (24·2-39·6) in the deferred treatment group. Grade 3-4 myelosuppression was reported in 33 (26%) of 128 patients who received treatment in the immediate chemotherapy group versus 24 (35%) of 68 patients who received treatment in the deferred chemotherapy group, neutropenia occurred in 49 (38%) versus 36 (53%) patients, respectively, and thrombocytopenia in 36 (28%) versus 26 (38%). Two patients died due to toxicity, one in each group. INTERPRETATION Our data did not show a significant improvement in overall survival with immediate versus deferred chemotherapy after radical cystectomy and bilateral lymphadenectomy for patients with muscle-invasive urothelial carcinoma. However, the trial is limited in power, and it is possible that some subgroups of patients might still benefit from immediate chemotherapy. An updated individual patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients. FUNDING Lilly, Canadian Cancer Society Research.

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study

UNLABELLED Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. INTRODUCTION The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. METHODS Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N = 65) or quarterly intravenous IBN (N = 122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. RESULTS Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9 ± 7.4 years, body mass index 23.8 ± 3.8 kg/m(2), BMD L1-L4 0.741 ± 0.100 g/cm(2), and TBS 1.208 ± 0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 % ± 6.3 vs. +2.9 % ± 3.3 and +4.3 % ± 6.6 vs. +0.3 % ± 4.1, respectively; P < 0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r (2) = 0.04) with no correlation between the changes in BMD and TBS over 24 months. CONCLUSIONS In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.

A pentasymmetric open channel blocker for Cys-loop receptor channels.

γ-Aminobutyric acid type A receptors (GABAA receptors) are chloride ion channels composed of five subunits, mediating fast synaptic and tonic inhibition in the mammalian brain. These receptors show near five-fold symmetry that is most pronounced in the second trans-membrane domain M2 lining the Cl- ion channel. To take advantage of this inherent symmetry, we screened a variety of aromatic anions with matched symmetry and found an inhibitor, pentacyanocyclopentdienyl anion (PCCP-) that exhibited all characteristics of an open channel blocker. Inhibition was strongly dependent on the membrane potential. Through mutagenesis and covalent modification, we identified the region α1V256-α1T261 in the rat recombinant GABAA receptor to be important for PCCP- action. Introduction of positive charges into M2 increased the affinity for PCCP- while PCCP- prevented the access of a positively charged molecule into M2. Interestingly, other anion selective cys-loop receptors were also inhibited by PCCP-, among them the Drosophila RDL GABAA receptor carrying an insecticide resistance mutation, suggesting that PCCP- could serve as an insecticide.

Comparative characterisation of two nitroreductases from Giardia lamblia as potential activators of nitro compounds

Giardia lamblia is a protozoan parasite that causes giardiasis, a diarrhoeal disease affecting humans and various animal species. Nitro drugs such as the nitroimidazole metronidazole and the nitrothiazolide nitazoxanide are used for treatment of giardiasis. Nitroreductases such as GlNR1 and GlNR2 may play a role in activation or inactivation of these drugs. The aim of this work is to characterise these two enzymes using functional assays. For respective analyses recombinant analogues from GlNR1 and GlNR2 were produced in Escherichia coli. E. coli expressing GlNR1 and GlNR2 alone or together were grown in the presence of nitro compounds. Furthermore, pull-down assays were performed using HA-tagged GlNR1 and GlNR2 as baits. As expected, E. coli expressing GlNR1 were more susceptible to metronidazole under aerobic and semi-aerobic and to nitazoxanide under semi-aerobic growth conditions whereas E. coli expressing GlNR2 were susceptible to neither drug. Interestingly, expression of both nitroreductases gave the same results as expression of GlNR2 alone. In functional assays, both nitroreductases had their strongest activities on the quinone menadione (vitamin K3) and FAD, but reduction of nitro compounds including the nitro drugs metronidazole and nitazoxanidewas clearly detected. Full reduction of 7-nitrocoumarin to 7-aminocoumarin was preferentially achieved with GlNR2. Pull-down assays revealed that GlNR1 and GlNR2 interacted in vivo forming a multienzyme complex. These findings suggest that both nitroreductases are multifunctional. Their main biological role may reside in the reduction of vitamin K analogues and FAD. Activation by GlNR1 or inactivation by GlNR2 of nitro drugs may be the consequence of a secondary enzymatic activity either yielding (GlNR1) or eliminating (GlNR2) toxic intermediates after reduction of these compounds. © 2015 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. This is an open access article under the CC BY-NC-ND license

The potential of female immigrants' integration into sport by intercultural clubs in Switzerland

Sport participation means a privileged access to participate in the sport system and the opportunities of actual integration into sport (Seiberth et al., 2013). The access to sport activities is often restricted for female immigrants. The function of sport participation concerning exercise offers of social associations is not a common theme in research on migration or on sports-related integration. Research on boundaries (Lamont & Molnár, 2002) suggest that gender-related and ethnic boundaries are stable behavioural and cognitive patterns leading to unequal social opportunities. The present study examined the potential of a Swiss intercultural club regarding female immigrants’ integration into sport by focussing on gender-related and ethnic boundaries. Ten interviews with female immigrants and conductress of an intercultural club plus a group discussion were held. Using qualitative content analysis and documentary method, findings reveal multifaceted, interwoven boundaries, e.g. maternal devotion, exclusive exercise offers for women, language learning devotion, religious need of headscarf. Otherwise resources to overcome boundaries are provided: Deploying competent employees; offering childcare, exercise offers suited to mothers‘ time schedule and language lessons; equitable, on integration focussed club-life. Thus, intercultural clubs might help to overcome boundaries and facilitate access to exercise for female immigrants and integrate them more successfully into sport than many sport clubs. A boundary focus and present data may open new perspectives for sport organisation and integration research. Further investigations of social associations offering exercise are advised.