51,473 research outputs found

    The Effective Dose and Pattern of Soybean Extract Administration to Regulate Body Weight of Laboratory Rats

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    Background: Protein in soybean, ÎČ conglycinin is responsible for anti-obesity effects by suppressing appetite via stimulation of Cholecystokinin. Cholecystokinin is a hormone released in the digestive tract in response to the intake of protein and suppress appetite for short-term. Detam 1 variety is a high-quality soybean according to the Minister of Agriculture of Indonesia. Soybean protein extract Detam 1 by Deak method contains high levels of ÎČ conglycinin. The purpose of this study was to determine the effective dose of protein extract Detam 1 soybean Deak Method (PEDSDM) in reducing food intake, regulate body weight, and plasma CCK level for 14 and 28 days at various dosage and pattern of treatment on male Wistar rats. Methods: There were eleven groups of treatment (n = 3), administrated with extracts at 5 mg/1x/day, 10 mg/1x/day, 20 mg/1x/day, 2.5 mg/2x/day, 5 mg/2x/day, 10 mg/2x/day and 1.7mg/3x/day, 3.4mg/3x/day, 6.7 mg/3x/day, negative control group (distilled water) and positive control group (Sibutramine). Food intake (g), weight loss (g) and measurement of plasma Cholecystokinin levels by ELISA (ng /ml) Results: The results showed that the highest percentage decrease in food intake is: group 3.4mg /3x/ day (p <0.05), inhibition weight gain for 14 days: group 10 mg /1x/ day, for 28 days: group 1.7 mg/3x/day (p <0.05), increased plasma Cholecystokinin levels: group 20 mg /1x/day (p <0.05). Conclusions: The effective dose and pattern administrating the rats for 14 days is extract of 10 mg once a day in the morning, for 28 days is 1.7 mg three times a day. (Health Science Journal of Indonesia 2016;7:17-26

    Mathematical Model Investigating the Effects of Neurostimulation Therapies on Neural Functioning: Comparing the Effects of Neuromodulation Techniques on Ion Channel Gating and Ionic Flux Using Finite Element Analysis

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    Neurostimulation therapies demonstrate success as a medical intervention for individuals with neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. Despite promising results from these treatments, the influence of an electric current on ion concentrations and subsequent transmembrane voltage is unclear. This project focuses on developing a unique cellular-level mathematical model of neurostimulation to better understand its e↔ects on neuronal electrodynamics. The mathematical model presented here integrates the Poisson-Nernst-Planck system of PDEs and Hodgkin-Huxley based ODEs to model the e↔ects of this neurotherapy on transmembrane voltage, ion channel gating, and ionic mobility. This system is decoupled using the Gauss-Seidel method and then the equations are solved using the finite element method on a biologically-inspired discretized domain. Results demonstrate the influence of transcranial electrical stimulation on membrane voltage, ion channel gating, and transmembrane flux. Simulations also compare the e↔ects of two di↔erent types of neurostimulation (transcranial electrical stimulation and deep brain stimulation) showcasing cellular-level di↔erences resulting from these distinct forms of electrical therapy. Hopefully this work will ultimately help elucidate the principles by which neurostimulation alleviates disease symptoms

    Classification in postural style

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    This article contributes to the search for a notion of postural style, focusing on the issue of classifying subjects in terms of how they maintain posture. Longer term, the hope is to make it possible to determine on a case by case basis which sensorial information is prevalent in postural control, and to improve/adapt protocols for functional rehabilitation among those who show deficits in maintaining posture, typically seniors. Here, we specifically tackle the statistical problem of classifying subjects sampled from a two-class population. Each subject (enrolled in a cohort of 54 participants) undergoes four experimental protocols which are designed to evaluate potential deficits in maintaining posture. These protocols result in four complex trajectories, from which we can extract four small-dimensional summary measures. Because undergoing several protocols can be unpleasant, and sometimes painful, we try to limit the number of protocols needed for the classification. Therefore, we first rank the protocols by decreasing order of relevance, then we derive four plug-in classifiers which involve the best (i.e., more informative), the two best, the three best and all four protocols. This two-step procedure relies on the cutting-edge methodologies of targeted maximum likelihood learning (a methodology for robust and efficient inference) and super-learning (a machine learning procedure for aggregating various estimation procedures into a single better estimation procedure). A simulation study is carried out. The performances of the procedure applied to the real data set (and evaluated by the leave-one-out rule) go as high as an 87% rate of correct classification (47 out of 54 subjects correctly classified), using only the best protocol.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS542 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials

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    STUDY QUESTION What is an objective approach that employs measurable and reproducible physiologic changes as the basis for the classification of ovarian hyperstimulation syndrome (OHSS) in order to facilitate more accurate reporting of incidence rates within and across clinical trials? SUMMARY ANSWER The OHSS flow diagram is an objective approach that will facilitate consistent capture, classification and reporting of OHSS within and across clinical trials. WHAT IS KNOWN ALREADY OHSS is a potentially life-threatening iatrogenic complication of the early luteal phase and/or early pregnancy after ovulation induction (OI) or ovarian stimulation (OS). The clinical picture of OHSS (the constellation of symptoms associated with each stage of the disease) is highly variable, hampering its appropriate classification in clinical trials. Although some degree of ovarian hyperstimulation is normal after stimulation, the point at which symptoms transition from those anticipated to those of a disease state is nebulous. STUDY DESIGN, SIZE, DURATION An OHSS working group, comprised of subject matter experts and clinical researchers who have significantly contributed to the field of fertility, was convened in April and November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS The OHSS working group was tasked with reaching a consensus on the definition and the classification of OHSS for reporting in clinical trials. The group engaged in targeted discussion regarding the scientific background of OHSS, the criteria proposed for the definition and the rationale for universal adoption. An agreement was reached after discussion with all members. MAIN RESULTS AND THE ROLE OF CHANCE One of the following conditions must be met prior to making the diagnosis of OHSS in the context of a clinical trial: (i) the subject has undergone OS (either controlled OS or OI) AND has received a trigger shot for final oocyte maturation (e.g. hCG, GnRH agonist [GnRHa] or kisspeptin) followed by either fresh transfer or segmentation (cryopreservation of embryos) or (ii) the subject has undergone OS or OI AND has a positive pregnancy test. All study patients who develop symptoms of OHSS should undergo a thorough examination. An OHSS flow diagram was designed to be implemented for all subjects with pelvic or abdominal complaints, such as lower abdominal discomfort or distention, nausea, vomiting and diarrhea, and/or for subjects suspected of having OHSS. The diagnosis of OHSS should be based on the flow diagram. LIMITATIONS, REASONS FOR CAUTION This classification system is primarily intended to address the needs of the clinical investigator undertaking clinical trials in the field of OS and may not be applicable for the use in clinical practice or with OHSS occurring under natural circumstances. WIDER IMPLICATIONS OF THE FINDINGS The proposed OHSS classification system will enable an accurate estimate of the incidence and severity of OHSS within and across clinical trials performed in women with infertility. STUDY FUNDING/COMPETING INTERESTS Financial support for the advisory group meetings was provided by Merck & Co., Inc., Kenilworth, NJ, USA. P.H. reports unrestricted research grants from MSD, Merck and Ferring, and honoraria for lectures from MSD, Merck and IBSA. S.M.N. reports that he has received fees and grant support from the following companies (in alphabetic order): Beckman Coulter, Besins, EMD Serono, Ferring Pharmaceuticals, Finox, MSD and Roche Diagnostics over the previous 5 years. P.D., C.C.C., J.L.F., H.M.F., and P.L. report no relationships that present a potential conflict of interest. B.C.T. reports: grants and honorarium from Merck Serono; unrestricted research grants, travel grants and honorarium, and participation in a company-sponsored speaker's bureau from Merck Sharp & Dohme; grants, travel grants, honoraria and advisory board membership from IBSA; travel grants from Ferring; and advisory board membership from Ovascience. L.B.S. reports current employment with Merck & Co, Inc., Kenilworth, NJ, USA, and owns stock in the company. K.G. and B.J.S. report prior employment with Merck & Co., Inc., Kenilworth, NJ, USA, and own stock in the company. All reported that competing interests are outside the submitted work. No other relationships or activities exist that could appear to have influenced the submitted work

    Specific lid-base contacts in the 26s proteasome control the conformational switching required for substrate degradation.

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    The 26S proteasome is essential for proteostasis and the regulation of vital processes through ATP-dependent degradation of ubiquitinated substrates. To accomplish the multi-step degradation process, the proteasomes regulatory particle, consisting of lid and base subcomplexes, undergoes major conformational changes whose origin is unknown. Investigating the Saccharomyces cerevisiae proteasome, we found that peripheral interactions between the lid subunit Rpn5 and the base AAA+ ATPase ring are important for stabilizing the substrate-engagement-competent state and coordinating the conformational switch to processing states upon substrate engagement. Disrupting these interactions perturbs the conformational equilibrium and interferes with degradation initiation, while later processing steps remain unaffected. Similar defects in early degradation steps are observed when eliminating hydrolysis in the ATPase subunit Rpt6, whose nucleotide state seems to control proteasome conformational transitions. These results provide important insight into interaction networks that coordinate conformational changes with various stages of degradation, and how modulators of conformational equilibria may influence substrate turnover

    Real-time optical manipulation of cardiac conduction in intact hearts

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    Optogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all‐optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide‐field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free‐run mode with submillisecond temporal resolution or in a closed‐loop fashion: a tailored hardware and software platform allowed real‐time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real‐time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real‐time resynchronization therapy and cardiac defibrillation. Furthermore, the closed‐loop approach was applied to simulate a re‐entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof‐of‐concept that a real‐time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart

    The Effectiveness of Vestibular Rehabilitation on Balance Related Impairments among Multiple Sclerosis Patients: A Systematic Review

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    Background: Balance related dysfunction remains a debilitating clinical manifestation among people with Multiple Sclerosis (pwMS) causing significant morbidity and reduced quality of life. Imbalance is found to stem primarily from neurophysiological causes. Current management strategies have shown to have small but clinically insignificant results with little consideration towards vestibular sources of postural instability. Vestibular rehabilitation (VR) provides a promising treatment strategy to mediate balance dysfunction among people with pwMS.Design: Systematic Review, guided by PRISMA guidelines and presenting a best evidence synthesis.Data sources: 10 electronic databases were searched from inception until September 2019.Eligibility criteria for study selection: Article of original research, population of patients with multiple sclerosis aged over 18, interventions detailing VR protocols, measurement of outcomes pre-VR/post-VR.Results: Seven articles satisfied the eligibility criteria. 6/7 studies were rated as high quality and regarded as level one evidence. 5 studies consisted of standardised VR protocols while 2 studies consisted of customised VR. All studies identified improvements of mixed significance in balance, fatigue and dizziness outcomes post VR. Heterogeneity among VR prescription patterns limited optimal prescription guidelines.Conclusions: The available evidence shows promise that VR is a safe and ef- fective strategy to provide short term benefits in balance related dysfunction in pwMS. Recommendations of mixed strength are made based on the quality of current literature. Current evidence for optimal prescription and long-term effects of VR is limited. Further high-level studies evaluating the effects of VR in patients with multiple sclerosis with vestibular and/or balance dysfunction are required

    Dual positive and negative regulation of GPCR signaling by GTP hydrolysis

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    G protein-coupled receptors (GPCRs) regulate a variety of intracellular pathways through their ability to promote the binding of GTP to heterotrimeric G proteins. Regulator of G protein signaling (RGS) proteins increase the intrinsic GTPase activity of G-subunits and are widely regarded as negative regulators of G protein signaling. Using yeast we demonstrate that GTP hydrolysis is not only required for desensitization, but is essential for achieving a high maximal (saturated level) response. Thus RGS-mediated GTP hydrolysis acts as both a negative (low stimulation) and positive (high stimulation) regulator of signaling. To account for this we generated a new kinetic model of the G protein cycle where GGTP enters an inactive GTP-bound state following effector activation. Furthermore, in vivo and in silico experimentation demonstrates that maximum signaling output first increases and then decreases with RGS concentration. This unimodal, non-monotone dependence on RGS concentration is novel. Analysis of the kinetic model has revealed a dynamic network motif that shows precisely how inclusion of the inactive GTP-bound state for the G produces this unimodal relationship
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