Reprogramming of hepatic fat accumulation and 'browning' of adipose tissue by the short-chain fatty acid acetate

Background/Objectives: Short-chain fatty acids, produced by microbiome fermentation of carbohydrates, have been linked to a reduction in appetite, body weight and adiposity. However, determining the contribution of central and peripheral mechanisms to these effects has not been possible. Subjects/Methods:C57BL/6 mice fed with either normal or high-fat diet were treated with nanoparticle-delivered acetate, and the effects on metabolism were investigated. Results:In the liver, acetate decreased lipid accumulation and improved hepatic function, as well as increasing mitochondrial efficiency. In white adipose tissue, it inhibited lipolysis and induced 'browning', increasing thermogenic capacity that led to a reduction in body adiposity. Conclusions:This study provides novel insights into the peripheral mechanism of action of acetate, independent of central action, including ‘browning’ and enhancement of hepatic mitochondrial function

Water and sodium intake habits and status of ultra-endurance runners during a multi-stage ultra-marathon conducted in a hot ambient environment: an observational field based study

<p>Abstract</p> <p>Background</p> <p>Anecdotal evidence suggests ultra-runners may not be consuming sufficient water through foods and fluids to maintenance euhydration, and present sub-optimal sodium intakes, throughout multi-stage ultra-marathon (MSUM) competitions in the heat. Subsequently, the aims were primarily to assess water and sodium intake habits of recreational ultra-runners during a five stage 225 km semi self-sufficient MSUM conducted in a hot ambient environment (T_max range: 32°C to 40°C); simultaneously to monitor serum sodium concentration, and hydration status using multiple hydration assessment techniques.</p> <p>Methods</p> <p>Total daily, pre-stage, during running, and post-stage water and sodium ingestion of ultra-endurance runners (UER, <it>n</it> = 74) and control (CON, <it>n</it> = 12) through foods and fluids were recorded on Stages 1 to 4 by trained dietetic researchers using dietary recall interview technique, and analysed through dietary analysis software. Body mass (BM), hydration status, and serum sodium concentration were determined pre- and post-Stages 1 to 5.</p> <p>Results</p> <p>Water (overall mean (SD): total daily 7.7 (1.5) L/day, during running 732 (183) ml/h) and sodium (total daily 3.9 (1.3) g/day, during running 270 (151) mg/L) ingestion did not differ between stages in UER (<it>p</it> < 0.001 <it>vs</it>. CON). Exercise-induced BM loss was 2.4 (1.2)% (<it>p</it> < 0.001). Pre- to post-stage BM gains were observed in 26% of UER along competition. Pre- and post-stage plasma osmolality remained within normal clinical reference range (280 to 303 mOsmol/kg) in the majority of UER (<it>p</it> > 0.05 <it>vs</it>. CON pre-stage). Asymptomatic hyponatraemia (<135 mmol/L) was evident pre- and post-stage in <it>n</it> = 8 UER, corresponding to 42% of sampled participants. Pre- and post-stage urine colour, urine osmolality and urine/plasma osmolality ratio increased (<it>p</it> < 0.001) as competition progressed in UER, with no change in CON. Plasma volume and extra-cellular water increased (<it>p</it> < 0.001) 22.8% and 9.2%, respectively, from pre-Stage 1 to 5 in UER, with no change in CON.</p> <p>Conclusion</p> <p>Water intake habits of ultra-runners during MSUM conducted in hot ambient conditions appear to be sufficient to maintain baseline euhydration levels. However, fluid over-consumption behaviours were evident along competition, irrespective of running speed and gender. Normonatraemia was observed in the majority of ultra-runners throughout MSUM, despite sodium ingestion under benchmark recommendations.</p

A generic travelling wave solution in dissipative laser cavity

A large family of cosh-Gaussian travelling wave solution of a complex Ginzburg–Landau equation (CGLE), that describes dissipative semiconductor laser cavity is derived. Using perturbation method, the stability region is identified. Bifurcation analysis is done by smoothly varying the cavity loss coefficient to provide insight of the system dynamics. He’s variational method is adopted to obtain the standard sech-type and the notso-explored but promising cosh-Gaussian type, travelling wave solutions. For a given set of system parameters, only one sech solution is obtained, whereas several distinct solution points are derived for cosh-Gaussian case. These solutions yield a wide variety of travelling wave profiles, namely Gaussian, near-sech, flat-top and a cosh-Gaussianwith variable central dip. A split-step Fourier method and pseudospectral method have been used for direct numerical solution of the CGLE and travelling wave profiles identical to the analytical profiles have been obtained. We also identified the parametric zone that promises an extremely large family of cosh-Gaussian travelling wave solutions with tunable shape. This suggests that the cosh-Gaussian profile is quite generic and would be helpful for further theoretical as well as experimental investigation on pattern formation, pulse dynamics andlocalization in semiconductor laser cavity

Common and Unique Contributions of Decorin-Binding Proteins A and B to the Overall Virulence of Borrelia burgdorferi

As an extracellular bacterium, the Lyme disease spirochete Borrelia burgdorferi resides primarily in the extracellular matrix and connective tissues and between host cells during mammalian infection, where decorin and glycosaminoglycans are abundantly found, so its interactions with these host ligands potentially affect various aspects of infection. Decorin-binding proteins (Dbps) A and B, encoded by a 2-gene operon, are outer surface lipoproteins with similar molecular weights and share approximately 40% identity, and both bind decorin and glycosaminoglycans. To investigate how DbpA and DbpB contribute differently to the overall virulence of B. burgdorferi, a dbpAB mutant was modified to overproduce the adhesins. Overproduction of either DbpA or DbpB resulted in restoration of the infectivity of the mutant to the control level, measured by 50% infectious dose (ID50), indicating that the two virulence factors are interchangeable in this regard. Overproduction of DbpA also allowed the mutant to disseminate to some but not all distal tissues slightly slower than the control, but the mutant with DbpB overproduction showed severely impaired dissemination to all tissues that were analyzed. The mutant with DbpA overproduction colonized all tissues, albeit generating bacterial loads significantly lower than the control in heart and joint, while the mutant overproducing DbpB remained severely defective in heart colonization and registered bacterial loads substantially lower than the control in joint. Taken together, the study indicated that DbpA and DbpB play a similar role in contribution to infectivity as measured by ID50 value but contribute differently to dissemination and tissue colonization

On the simple random-walk models of ion-channel gate dynamics reflecting long-term memory

Several approaches to ion-channel gating modelling have been proposed. Although many models describe the dwell-time distributions correctly, they are incapable of predicting and explaining the long-term correlations between the lengths of adjacent openings and closings of a channel. In this paper we propose two simple random-walk models of the gating dynamics of voltage and Ca2+-activated potassium channels which qualitatively reproduce the dwell-time distributions, and describe the experimentally observed long-term memory quite well. Biological interpretation of both models is presented. In particular, the origin of the correlations is associated with fluctuations of channel mass density. The long-term memory effect, as measured by Hurst R/S analysis of experimental single-channel patch-clamp recordings, is close to the behaviour predicted by our models. The flexibility of the models enables their use as templates for other types of ion channel

Optimal Estimation of Ion-Channel Kinetics from Macroscopic Currents

Markov modeling provides an effective approach for modeling ion channel kinetics. There are several search algorithms for global fitting of macroscopic or single-channel currents across different experimental conditions. Here we present a particle swarm optimization(PSO)-based approach which, when used in combination with golden section search (GSS), can fit macroscopic voltage responses with a high degree of accuracy (errors within 1%) and reasonable amount of calculation time (less than 10 hours for 20 free parameters) on a desktop computer. We also describe a method for initial value estimation of the model parameters, which appears to favor identification of global optimum and can further reduce the computational cost. The PSO-GSS algorithm is applicable for kinetic models of arbitrary topology and size and compatible with common stimulation protocols, which provides a convenient approach for establishing kinetic models at the macroscopic level

The learners' perspective on internal medicine ward rounds: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Ward rounds form an integral part of Internal Medicine teaching. This study aimed to determine the trainees' opinions regarding various aspects of their ward rounds, including how well they cover their learning needs, how they would like the rounds to be conducted, and differences of opinion between medical students and postgraduates.</p> <p>Methods</p> <p>A cross-sectional study was conducted on a total of 134 trainees in Internal Medicine, comprising medical students, interns, residents and fellows, who were asked to fill in a structured, self-designed questionnaire. Most of the responses required a rating on a scale of 1-5 (1 being highly unsatisfactory and 5 being highly satisfactory).</p> <p>Results</p> <p>Teaching of clinical skills and bedside teaching received the lowest overall mean score (Mean ± SD 2.48 ± 1.02 and 2.49 ± 1.12 respectively). They were rated much lower by postgraduates as compared to students (p < 0.001). All respondents felt that management of patients was the aspect best covered by the current ward rounds (Mean ± SD 3.71 ± 0.72). For their desired ward rounds, management of patients received the highest score (Mean ± SD 4.64 ± 0.55), followed by bedside examinations (Mean ± SD 4.60 ± 0.61) and clinical skills teaching (Mean ± SD 4.50 ± 0.68). The postgraduates desired a lot more focus on communication skills, counselling and medical ethics as compared to students, whose primary focus was teaching of bedside examination and management. A majority of the respondents (87%) preferred bedside rounds over conference room rounds. Even though the duration of rounds was found to be adequate, a majority of the trainees (68%) felt there was a lack of individual attention during ward rounds.</p> <p>Conclusions</p> <p>This study highlights important areas where ward rounds need improvement in order to maximize their benefit to the learners. There is a need to modify the current state of ward rounds in order to address the needs and expectations of trainees.</p

Quinoline Group Modified Carbon Nanotubes for the Detection of Zinc Ions

Carbon nanotubes (CNTs) were covalently modified by fluorescence ligand (glycine-N-8-quinolylamide) and formed a hybrid material which could be used as a selective probe for metal ions detection. The anchoring to the surface of the CNTs was carried out by the reaction between the precursor and the carboxyl groups available on the surface of the support. Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA) unambiguously proved the existence of covalent bonds between CNTs and functional ligands. Fluorescence characterization shows that the obtained organic–inorganic hybrid composite is highly selective and sensitive (0.2 μM) to Zn(II) detection

Total Pelvic Exenteration for Primary and Recurrent Malignancies

Contains fulltext : 81087.pdf (publisher's version ) (Open Access)INTRODUCTION: Complete resection is the most important prognostic factor in surgery for pelvic tumors. In locally advanced and recurrent pelvic malignancies, radical margins are sometimes difficult to obtain because of close relation to or growth in adjacent organs/structures. Total pelvic exenteration (TPE) is an exenterative operation for these advanced tumors and involves en bloc resection of the rectum, bladder, and internal genital organs (prostate/seminal vesicles or uterus, ovaries and/or vagina). METHODS: Between 1994 and 2008, a TPE was performed in 69 patients with pelvic cancer; 48 with rectal cancer (32 primary and 16 recurrent), 14 with cervical cancer (1 primary and 13 recurrent), 5 with sarcoma (3 primary and 2 recurrent), 1 with primary vaginal, and 1 with recurrent endometrial carcinoma. Ten patients were treated with neoadjuvant chemotherapy and 66 patients with preoperative radiotherapy to induce down-staging. Eighteen patients received IORT because of an incomplete or marginal complete resection. RESULTS: The median follow-up was 43 (range, 1-196) months. Median duration of surgery was 448 (range, 300-670) minutes, median blood loss was 6,300 (range, 750-21,000) ml, and hospitalization was 17 (range, 4-65) days. Overall major and minor complication rates were 34% and 57%, respectively. The in-hospital mortality rate was 1%. A complete resection was possible in 75% of all patients, a microscopically incomplete resection (R1) in 16%, and a macroscopically incomplete resection (R2) in 9%. Five-year local control for primary locally advanced rectal cancer, recurrent rectal cancer, and cervical cancer was 89%, 38%, and 64%, respectively. Overall survival after 5 years for primary locally advanced rectal cancer, recurrent rectal cancer, and cervical cancer was 66%, 8%, and 45%. CONCLUSIONS: Total pelvic exenteration is accompanied with considerable morbidity, but good local control and acceptable overall survival justifies the use of this extensive surgical technique in most patients, especially patients with primary locally advanced rectal cancer and recurrent cervical cancer