Τρίτη, 9 Αυγούστου 2016

Granule cell excitability regulates gamma and beta oscillations in a model of the olfactory bulb dendrodendritic microcircuit

Odors evoke gamma (40–100 Hz) and beta (20–30 Hz) oscillations in the local field potential (LFP) of the mammalian olfactory bulb (OB). Gamma (and possibly beta) oscillations arise from interactions in the dendrodendritic microcircuit between excitatory mitral cells (MCs) and inhibitory granule cells (GCs). When cortical descending inputs to the OB are blocked, beta oscillations are extinguished whereas gamma oscillations become larger. Much of this centrifugal input targets inhibitory interneurons in the GC layer and regulates the excitability of GCs, which suggests a causal link between the emergence of beta oscillations and GC excitability. We investigate the effect that GC excitability has on network oscillations in a computational model of the MC-GC dendrodendritic network with Ca2+-dependent graded inhibition. Results from our model suggest that when GC excitability is low, the graded inhibitory current mediated by NMDA channels and voltage-dependent Ca2+ channels (VDCCs) is also low, allowing MC populations to fire in the gamma frequency range. When GC excitability is increased, the activation of NMDA receptors and other VDCCs is also increased, allowing the slow decay time constants of these channels to sustain beta-frequency oscillations. Our model argues that Ca2+ flow through VDCCs alone could sustain beta oscillations and that the switch between gamma and beta oscillations can be triggered by an increase in the excitability state of a subpopulation of GCs.



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Motor learning and cross-limb transfer rely upon distinct neural adaptation processes

Performance benefits conferred in the untrained limb after unilateral motor practice are termed cross-limb transfer. Although the effect is robust, the neural mechanisms remain incompletely understood. In this study we used noninvasive brain stimulation to reveal that the neural adaptations that mediate motor learning in the trained limb are distinct from those that underlie cross-limb transfer to the opposite limb. Thirty-six participants practiced a ballistic motor task with their right index finger (150 trials), followed by intermittent theta-burst stimulation (iTBS) applied to the trained (contralateral) primary motor cortex (cM1 group), the untrained (ipsilateral) M1 (iM1 group), or the vertex (sham group). After stimulation, another 150 training trials were undertaken. Motor performance and corticospinal excitability were assessed before motor training, pre- and post-iTBS, and after the second training bout. For all groups, training significantly increased performance and excitability of the trained hand, and performance, but not excitability, of the untrained hand, indicating transfer at the level of task performance. The typical facilitatory effect of iTBS on MEPs was reversed for cM1, suggesting homeostatic metaplasticity, and prior performance gains in the trained hand were degraded, suggesting that iTBS interfered with learning. In stark contrast, iM1 iTBS facilitated both performance and excitability for the untrained hand. Importantly, the effects of cM1 and iM1 iTBS on behavior were exclusive to the hand contralateral to stimulation, suggesting that adaptations within the untrained M1 contribute to cross-limb transfer. However, the neural processes that mediate learning in the trained hemisphere vs. transfer in the untrained hemisphere appear distinct.



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Efficient CRISPR-Mediated Post-transcriptional Gene Silencing in a Hyperthermophilic Archaeon Using Multiplexed crRNA Expression

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) -mediated RNA degradation is catalyzed by a type III system in the hyperthermophilic archaeon Sulfolobus solfataricus. Earlier work demonstrated that the system can be engineered to target specifically mRNA of an endogenous host reporter gene, namely the β-galactosidase in S. solfataricus. Here we investigated the effect of single and multiple spacers targeting the mRNA of a second reporter gene, α-amylase, at the same and at different locations respectively, by using a minimal CRISPR (miniCR) locus supplied on a viral shuttle vector. The use of increasing numbers of spacers reduced mRNA levels at progressively higher levels, with three crRNAs (CRISPR RNAs) leading to approximately 70 to 80% reduction and five spacers resulting in an α-amylase gene knockdown of > 90% measured on both mRNA and protein activity levels. Our results indicate that this technology can be used to increase or modulate gene knockdown for efficient post-transcriptional gene silencing in hyperthermophilic archaea and potentially also in other organisms.



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Synaptic integration of transplanted interneuron progenitor cells into native cortical networks

Interneuron-based cell transplantation is a powerful method to modify network function in a variety of neurological disorders, including epilepsy. Whether new interneurons integrate into native neural networks in a subtype-specific manner is not well understood, and the therapeutic mechanisms underlying interneuron-based cell therapy, including the role of synaptic inhibition, are debated. In this study, we tested subtype-specific integration of transplanted interneurons using acute cortical brain slices and visualized patch-clamp recordings to measure excitatory synaptic inputs, intrinsic properties, and inhibitory synaptic outputs. Fluorescently labeled progenitor cells from the embryonic medial ganglionic eminence (MGE) were used for transplantation. At 5 wk after transplantation, MGE-derived parvalbumin-positive (PV+) interneurons received excitatory synaptic inputs, exhibited mature interneuron firing properties, and made functional synaptic inhibitory connections to native pyramidal cells that were comparable to those of native PV+ interneurons. These findings demonstrate that MGE-derived PV+ interneurons functionally integrate into subtype-appropriate physiological niches within host networks following transplantation.



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Glucose or Altered Ceramide Biosynthesis Mediate Oxygen Deprivation Sensitivity Through Novel Pathways Revealed by Transcriptome Analysis in Caenorhabditis elegans

Individuals with type 2 diabetes display metabolic abnormalities, such as hyperglycemia, increased free fatty acids, insulin resistance, and altered ceramide levels, that contribute to vascular dysfunctions and compromised oxygen delivery. Caenorhabditis elegans fed a glucose-supplemented diet or with altered ceramide metabolism, due to a hyl-2 mutation, are sensitive to oxygen deprivation (anoxia). Our experiments showed that the combination of these factors further decreased the anoxia survival. RNA-sequencing analysis was performed to assess how a glucose-supplemented diet and/or a hyl-2 mutation altered the transcriptome. Comparison analysis of transcripts associated with anoxia sensitive animals (hyl-2(tm2331) mutation or a glucose diet) revealed 199 common transcripts encoded by genes with known or predicted functions involving innate immunity, cuticle function (collagens) or xenobiotic and endobiotic phase I and II detoxification system. Use of RNA interference (RNAi) to target gene products of the xenobiotic and endobiotic phase I and II detoxification system (UDP-glycosyltransferase and Cytochrome p450 genes; ugt-15, ugt-18, ugt-19, ugt-41, ugt-63, cyp-13A12, cyp-25A1 and cyp-33C8) increased anoxia survival in wild-type animals fed a standard diet. Anoxia sensitivity of the hyl-2(tm2031) animals was suppressed by RNAi of cyp-25A1 or cyp-33C8 genes. A glucose diet fed to the P0 hermaphrodite decreased the anoxia survival of its F1 embryos, however, the RNAi of ugt-63 and cyp-33C8 suppressed anoxia sensitivity. These studies provide evidence that the detoxification system impacts oxygen deprivation responses and that C. elegans can be used to model the conserved detoxification system.



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Assessment of the expression and role of the {alpha}1-nAChR subunit in efferent cholinergic function during the development of the mammalian cochlea

Hair cell (HC) activity in the mammalian cochlea is modulated by cholinergic efferent inputs from the brainstem. These inhibitory inputs are mediated by calcium-permeable nicotinic acetylcholine receptors (nAChRs) containing α9- and α10-subunits and by subsequent activation of calcium-dependent potassium channels. Intriguingly, mRNAs of α1- and -nAChRs, subunits of the "muscle-type" nAChR have also been found in developing HCs (Cai T, Jen HI, Kang H, Klisch TJ, Zoghbi HY, Groves AK. J Neurosci 35: 5870–5883, 2015; Scheffer D, Sage C, Plazas PV, Huang M, Wedemeyer C, Zhang DS, Chen ZY, Elgoyhen AB, Corey DP, Pingault V. J Neurochem 103: 2651–2664, 2007; Sinkkonen ST, Chai R, Jan TA, Hartman BH, Laske RD, Gahlen F, Sinkkonen W, Cheng AG, Oshima K, Heller S. Sci Rep 1: 26, 2011) prompting proposals that another type of nAChR is present and may be critical during early synaptic development. Mouse genetics, histochemistry, pharmacology, and whole cell recording approaches were combined to test the role of α1-nAChR subunit in HC efferent synapse formation and cholinergic function. The onset of α1-mRNA expression in mouse HCs was found to coincide with the onset of the ACh response and efferent synaptic function. However, in mouse inner hair cells (IHCs) no response to the muscle-type nAChR agonists (±)-anatoxin A, (±)-epibatidine, (–)-nicotine, or 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) was detected, arguing against the presence of an independent functional α1-containing muscle-type nAChR in IHCs. In α1-deficient mice, no obvious change of IHC efferent innervation was detected at embryonic day 18, contrary to the hyperinnervation observed at the neuromuscular junction. Additionally, ACh response and efferent synaptic activity were detectable in α1-deficient IHCs, suggesting that α1 is not necessary for assembly and membrane targeting of nAChRs or for efferent synapse formation in IHCs.



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Brain-derived neurotrophic factor differentially modulates excitability of two classes of hippocampal output neurons

Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampus-dependent learning and memory. Canonically, this has been ascribed to an enhancing effect on neuronal excitability and synaptic plasticity in the CA1 region. However, it is the pyramidal neurons in the subiculum that form the primary efferent pathways conveying hippocampal information to other areas of the brain, and yet the effect of BDNF on these neurons has remained unexplored. We present new data that BDNF regulates neuronal excitability and cellular plasticity in a much more complex manner than previously suggested. Subicular pyramidal neurons can be divided into two major classes, which have different electrophysiological and morphological properties, different requirements for the induction of plasticity, and different extrahippocampal projections. We found that BDNF increases excitability in one class of subicular pyramidal neurons yet decreases excitability in the other class. Furthermore, while endogenous BDNF was necessary for the induction of synaptic plasticity in both cell types, BDNF enhanced intrinsic plasticity in one class of pyramidal neurons yet suppressed intrinsic plasticity in the other. Taken together, these data suggest a novel role for BDNF signaling, as it appears to dynamically and bidirectionally regulate the output of hippocampal information to different regions of the brain.



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Knockout of the BK {beta}4-subunit promotes a functional coupling of BK channels and ryanodine receptors that mediate a fAHP-induced increase in excitability

BK channels are large-conductance calcium- and voltage-activated potassium channels with diverse properties. Knockout of the accessory BK β4-subunit in hippocampus dentate gyrus granule neurons causes BK channels to change properties from slow-gated type II channels to fast-gated type I channels that sharpen the action potential, increase the fast afterhyperpolarization (fAHP) amplitude, and increase spike frequency. Here we studied the calcium channels that contribute to fast-gated BK channel activation and increased excitability of β4 knockout neurons. By using pharmacological blockers during current-clamp recording, we find that BK channel activation during the fAHP is dependent on ryanodine receptor activation. In contrast, L-type calcium channel blocker (nifedipine) affects the BK channel-dependent repolarization phase of the action potential but has no effect on the fAHP. Reducing BK channel activation during the repolarization phase with nifedipine, or during the fAHP with ryanodine, indicated that it is the BK-mediated increase of the fAHP that confers proexcitatory effects. The proexcitatory role of the fAHP was corroborated using dynamic current clamp. Increase or decrease of the fAHP amplitude during spiking revealed an inverse relationship between fAHP amplitude and interspike interval. Finally, we show that the seizure-prone ryanodine receptor gain-of-function (R2474S) knockin mice have an unaltered repolarization phase but larger fAHP and increased AP frequency compared with their control littermates. In summary, these results indicate that an important role of the β4-subunit is to reduce ryanodine receptor-BK channel functional coupling during the fAHP component of the action potential, thereby decreasing excitability of dentate gyrus neurons.



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AN IMPACT OF EDUCATIONAL INTERVENTION OF ADVERSE DRUG REACTIONS REPORTING TO AMC-PvPI AMONG NURSES IN TERTIARY CARE TEACHING HOSPITAL

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Venkata RamaRao Nallani*, Dr.Rama Rao Nadendla, Dr. Zahedabano.
educational intervention was evaluated by using Chi square test & Fischer exact test in graph pad prism version (6.0). RESULTS: A total 180 nurses were involved in Pre KAP and Post KAP survey questionnaire. The overall response rates between pre intervention and post intervention was statistically significant for nurses (P value

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SYNTHESIS AND CHARACTERIZATION OF 1-PHENYL-3-[4-(2-SUBSTITUTEDIMINO-4-SUBSTITUTEDIMINO-1,3,5-DITHIAZINO)AMINOPHENYL]-PROP-2-ENE-1-ONES

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Dipak T. Tayade*, Sanghapal S. Padhen.
Recently in this laboratory series of 1-phenyl-3-[4-(2-substitued imino-4-substituted imino-1,3,5-dithiazino)-aminophenyl]-prop-2-ene-1-ones (VIIIaa-ae)had been synthesized by the interaction of 1-phenyl-3-[4-(5-allyl-2,4-dithiobiureto) phenyl]-Prop-2-ene-1-ones (Va) with various isocyanodichlorides (VIIa-e) in acetone medium. The reaction mixture was reflux 4 hours and filtered in hot condition. After distillation of excess of solvents crystals were isolated out, this on basification with ammonium hydroxide gave product The structure of all synthesized compounds were justified on the basis of chemical characteristics, elemental analysis and spectral studies.


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IN-VITRO ANTI-HELMENTHIC ACTIVITY OF AQUEOUS LEAF EXTRACT OF CALOTROPIS GIGANTEAN

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
N.Saikrishna*, G. VijayaKumar, V. L. Sravani, S. VR. SatyaDeepthi, S. S. Margarate, P. chandana. V. Ratnakumari.
The present research work is carried out to evaluate the invitro antihelminthetic activity of aqueous leaf extract of calotropis gigantean. The various concentrations of aqeous leaf extract of calotropis giganteant was prepared in 20mg,40mg and 60mg/ml and tested in invitro study on Indian earthworm (Pheretima posthuma), Albendazole was taken reference standard drug in different concentrations 20mg, 40mg and 60mg/ml whereas distilled water as control. The time taken for paralysis and death of worms were recorded. Dose dependent antihelmintic activity was observed for aqueous leaf extract. The antihelmintic activity of calotropis gigantean found was better than the standard drug.


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FORMULATION, DEVLOPMENT and CHARECTERIZATION OF ORAL FAST DISSOLVING FILM OF LEVOCETRIZINE DIHYDROCHLORIDE

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Sandeep V. Gapat*, Prof. Ram S. Pentewar, Dr. Anoop Singh, R. D. Ingole, Vijayananda Khadkutkar.
Aim of the present study was to develop the Fast Dissolving Oral Films of Levocetirizine Hydrochloride, a non sedative antihistamine drug. Chemically, Levocetirizine is the active enantiomer of Cetirizine. Fast dissolving oral films deliver drug directly in the vascular system and bypasses the hepatic first pass metabolism so dose of the drug may also reduce significantly. Fast dissolving films were prepared using solvent casting method, hydrophilic polymers (HPMC15cps, HPMC15cps) were selected as film forming agents and propylene glycol was used as plasticizer to give flexibility to the films. In FT-IR study no interaction was observed between drug and the excipients. Blank films were prepared and evaluated. Concentration of polymer was optimized during preliminary studies. Three blank films were selected for the incorporation of drug. After characterization the drug loaded films and studying their disintegration time & In-Vitro drug release studies, among the formulations F1-F18, F2, F8, F10 & F18 was selected the best formulation as its disintegration and dissolution time was less and it release drug to a greater extent compared to other formulations with minimum time. As dose of the drug gets reduced from 5 mg to just 2 mg, therefore adverse effects of the drug may also get reduced. Therefore fast dissolving oral films can play an important role in oral drug delivery.


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HPLC SEPARATION OF PIDOTIMOD ENANTIOMERS USING BETA-CYCLODEXTRIN BASED CHIRAL STATIONARY PHASE

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Madhuri Baghel, Sadhana J. Rajput*.
A simple, sensitive, specific, precise, and rapid isocratic chiral RP-HPLC method was developed and validated for estimation of R and S enantiomers of Pidotimod, a potent dipeptide immunomodulator. The separation was achieved with LICHROCART CHIRADEX (150×4.6mm, 5μm) column at wavelength of 215 nm. The mobile phase was ammonium acetate buffer and methanol in the ration of 85:15 at flow rate of 0.8 ml/ min. The developed method was validated as per ICH guideline which was linear over the range of 50-250 μg/ml with LOD and LOQ of 1.2072 and 3.6583 respectively. The %RSD for repeatability and Intermediate precision was found to be less than 2. The elution of enantiomeric peaks of Pidotimod was further confirmed by LC-MS/MS analysis. The developed method could be utilized for estimation of pidotimod enantiomers.


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FORMULATION AND EVALUATION OF GASTRORETENSIVE FLOATING TABLETS OF VENLAFAXINE HCl

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
N. Lakshmi Prasanthi*, Ayya. Rajendra Prasad, K. Durga, M. Durga Nageswara Rao.
The purpose of the study was to develop the gastro retentive floating tablets of venlafaxine HCl is an antidepressant which are designed to increase the gastric residence time, thus prolonging the drug release in the present study The tablets were prepared by direct compression technique using different polymers like HPMC K4M, Carbopol 940 and sodium bicarbonate as gas generating agent. The prepared tablets were evaluated for different parameters like hardness, friability, uniformity of weight, in vitro buoyancy studies, and in vitro dissolution studies. The FTIR studies revealed that there was no interaction between the drug and excipients. The tablets containing weight variation of 0.17mg±0.15mg to 0.62mg±0.36mg, hardness of 4.2kg/cm2±0.34kg/cm2 to 5.2kg/cm2±0.63kg/cm2, percentage friability was found to be less than one, thickness of 3mm±0.27mm to 4.6mm±0.025mm, venlafaxine HCl released 92.25±2.9 to 93.35±2.1% of the drug at the end of 10th hour by in vitro release study. The formulation F9 was selected as an optimized formula because it gave best results in terms of the required in vitro buoyancy study, good floating integrity, and drug release in sustained release manner and best fitted to zero order release kinetics with r2 value of 0.94.


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FORMULATION AND EVALUATION OF LIPOSOMAL GEL CONTAINING ANTIFUNGAL ACTIVITY – KETOCONAZOLE

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Deevan Paul*, Vothani Sarath Babu.
Liposomal carriers, well known for their potential in topical drug delivery have been chosen to help fungal infections in the skin layers. A development of system which controls the release and enhances the bioavailability of Ketoconazole, an fungal activity is in demand. In the present work statistical study for the formulation of Liposomes for topical delivery of Ketoconazole Liposomal gel using the factorial design approach was undertaken. Ketoconazole, Soya lecithin, Cholesterol were dissolved in mixture of chloroform and methanol (9:1) were taken in different levels and liposomes were prepared using thin film hydration technique. Gel containing Liposomes for optimised batch were prepared in Carbopol® 940. The FT-IR spectroscopy study was carried out to check out the compatibility between the drug Ketoconazole and the excipients used for the preparation. These include average particle size and size distribution, shape, encapsulation efficiency, Percentage drug content, In-vitro drug release study. The compatibility study of the prepared Ketoconazole Liposomes showed no interaction between drug and excipients. The size of liposomal formulations ranged from 3.278- 19.688μm. The entrapment efficiency of drug increased when molar ratio of lipid to cholesterol was changed from 1:1% Drug content of liposomal formulations obtained shows 94.6 - 99.2% drug content. Liposomal dispersion and gel were found to increase the skin permeation and deposition compared to control and marketed gel. Hence it can be concluded that Ketoconazole can also be loaded in liposomal carriers which found to be effective, stable and can be preceded for further future studies.


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ESTIMATION OF ANTI-DIABETIC TENELIGLIPTIN HYDROBROMIDE HYDRATE BY RP-HPLC AND DERIVATIVE SPECTROSCOPIC METHOD

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Sohan S. Chitlange*, Diptee G. Rawat, Sneha Chandani.
Simple, accurate, precise and economical HPLC and UV method has been developed and validated for the estimation of teneligliptin hydrobromide hydrate (THH) in bulk and tablet dosage form. Isocratic elution at the flow rate of 1.0 ml/min was employed on a Kromasil 100-5-C8 column at ambient temperature. The mobile phase consisted of Methanol: 0.025M phosphate buffer pH adjusted to 3 with o-phosphoric acid (60:40 v/v). The detection wavelength was at 254nm. Linearity was observed in the concentration range of 10-100 μg/ml. The retention time for Teneligliptin was 4.14 min. In stability testing, teneligliptin was found susceptible to alkali hydrolysis and oxidatative degradation. Because the method could effectively separate the drug from its degradation products, it can be used as a stability indicating method. First order derivative UV spectrophotometric method was also developed using methanol as solvent at analytical λ 261.0 nm. Beers law was obeyed in the concentration range of 5-50 μg/ml and r2 =0.9996. The proposed methods were validated according to the ICH guidelines. Both the developed methods are accurate and precise and can be used for routine quality control analysis of Teneligliptin in bulk and pharmaceutical formulation. In case of HPLC as well resolved peak is obtained for Teneligliptin after degradation, method is also suitable for stability studies.


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EFFECT OF PECTIN-TAGGED SILVER NANOCOMPOSITE ON A-72 CANCER CELL LINE

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Emmanuel U. Nwakwasi, Baisakhi Moharana, M. Parthiban, S. P. Preetha.
The pectin-tagged silver nanocomposite was explored for its antitumor properties against A-72 (Canine fibroblast tumor) cancer cell line. Pectin is a natural polysaccharide found in high amounts in most cell wall of plants. It is non-toxic in nature and functions as both intercellular and intracellular cementing material in addition to its chemo-preventive and anti-tumor activities against some aggressive, recurrent cancers. Thus, to improve the efficacy of pectin and to reduce the dose, it was conjugated into a silver nanocomposite. The synthesized silver nanocomposite, pectin powder and pectin-tagged silver nanocomposite were analyzed by high resolution scanning electron microscopy (HR-SEM), Fourier Transform Infra-Red Spectroscopy (FTIR), X-Ray Diffraction (XRD), UV-Vis Spectroscopy, zeta potential and entrapment efficiency so as to determine the size, morphology, stability and various functional groups of the composite. Their possible anticancer activity against A-72 cancer cells were further evaluated by MTT cytotoxicity Assay. The Zeta Potential analysis of the synthesized AgNPs and pectin-tagged silver nanocomposite were found to be +59.2 mV and 25.9 mV respectively which indicate a good and fair stability. Conclusively, with an average diameter of 42nm revealed by HR-SEM, the pectin-tagged silver nanocomposite exhibited a very significant cytotoxic effect on A-72 cancer cell line when compared with the standard anticancer drug (Fluorouracil/5-FU) by attaining a maximum inhibition percentage of 85.88% which is comparable to 88.88% of fluorouracil/5-FU. This clearly indicates the antitumor efficacy of the synthesized nanocomposite when conjugated with pectin and thus, proved to be a potential anticancer drug.


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EVALUATION OF SILVER BIO-NANOPARTICLES SYNTHESIZED WITH THE MEDIATION OF ZIZYPHUS JUJUBA FRUIT EXTRACT ON BACTERICIDAL COMPATIBILITY AND SEED VIABILITY

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
N. Vasanth*, G. Melchias, P. Kumaravel.
Nanoparticles that are synthesized via green methods have become a substantial source of molecules for alternative diagnosis and treatment strategies in medical industry. The conventional methods of synthesis of nanoparticles (NPs) are often negated by the inconsistency in the process and also being a source of aggressive toxic levels in the environment. Our investigation demonstrates the potentials of silver nanoparticles synthesized with the mediation of Zizyphus jujuba to be ecofriendly and advantageous over their counterparts of similar methods. Their evaluation for bactericidal compatibility makes new ways of production of stable NPs. The NPs were characterized using UV-visible spectrophotometer, X-ray diffractometer (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). The Green mediated synthesis of silver nanoparticles which shows maximum zones of inhibition against human pathogens and it also enhance the seed germination growth of Vigna unguiculata, Macrotyloma uniflorum and Lablab purpureus.


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A COMPARATIVE EVALUATION OF GYMNEMIC ACIDS AND EXTRACT OF SYLVESTRE FOR ITS ANTI-HYPERGLYCEMIC ACTIVITY

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Vasukeshetty, Kalakotla Shanker, Jayaveera, Venkatesham Allenki*.
The present study is designed to evaluate the antihyperglycemic activity of Gymnemic acids and extract of sylvestre on alloxan induced diabetic male Wistar rats. Gymnemic acids of sylvestre significantly decrease the blood glucose levels (p

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STUDY OF DRUG-DRUG INTERACTION IN MEDICINE DEPARTMENT OF A TERTIARY CARE TEACHING HOSPITAL

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Safdar M*, Nataraj G.R, Nivil Joseph, Neethu George.
Many drugs are going to be prescribed in patients who admitted to medicine department. These drugs are capable of causing a number of adverse drug-drug interactions (DDI) some of which may be fatal. Polypharmacy is one of the leading cause of DDI in patients. Thus DDI associated with these drugs may lead to non-compliance and at times discontinuation of therapy. To evaluate drug-drug interactions in patients admitted in medicine department. It is a prospective-observational study. This study included hospital out-patients treated in Medicine department. Data was collected from the medical records of In-patients which includes patients demographic details, medication history, social history, treatment chart, status and drug-drug interaction is assessed by using micromedex and other tertiary resources and documented in a suitably designed data collection form. A total of 200 patients were enrolled in the study in that 36% are belonging to age group 31-50. More patients were males.41.5% moderate interactions and 11.5% mild interactions were found. Number of drugs prescribed and age is playing an important role in drug-drug interaction.


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IN VITRO ANTI - CLASTOGENIC ACTIVITIES OF DIFFERENT FRACTIONS OF ROOT OF LAWSONIA INERMIS ON CALF THYMUS DNA MOLECULE BY GEL ELECTROPHORESIS

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
MinaBasirian*, V. Ch. Jeevani, S. N. Manjula, K. Mruthunjaya.
Back ground: Most of the mutations are due to clastogens, hence finding the potent anti-oxidants which inhibit the mutation is very important. In vitro anti-clastogenic activity of different fractions (extraction) of roots of Lawsonia inermis (LI), on calf thymus DNA, against cigarette smoke, CYCLO (cyclophosphamide) and hydroxyl radical as clastogens, were studied. These clastogens lead to breakdown of the DNA molecule and mutation, hence present study focused on effect different fractions of LI which are having anti-oxidants property to prevent DNA strand break. Methods: Anti-clastogenic activity of different fractions of LI namely ethyle acetate (LIEAC), alcoholic (LIALC), petroleum ether (LIPET), buthanol (LIBUT) and aqueous (LIAQ) were evaluated on calf thymus DNA by agarose gel electrophoresis against CYCLO (cyclophosphamide), cigarette smoke and hydroxyl radical (Fenton reaction) as clastogens. DNA strand after exposure to different clastogens were breaking, based on different clastogens , formation of different sized breakage of DNA were observed on UV illumination with help of dye. Here the clastogens were breaking the DNA stand and prevention of the breaking down was observed for different fractions of LI. Results: Protection (inhibit the breaking of DNA strand) of Calf thymus DNA against Fenton reaction, CYCLO, cigarette, smoke induced damage was observed in all the fractions of LI due to their anti-oxidant activity, but LIEAC , LIALC and LIBUT showed more protective activity ,and reduced the DNA strand break Conclusion: LI fractions showed protective and anti-clastogenic activity against clastogens which induced mutation. The protective activity of different fraction was due to anti-oxidant property which is directly related to total phenolic and flavonoid content but still further investigation required to claim the protective activity of these fractions.


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RANDOMIZED CONTROLLED TRIAL OF TRANEXAMIC ACID AMONG PARTURIENTS AT INCREASED RISK FOR POSTPARTUM HEMORRHAGE UNDERGOING CESAREAN DELIVERY IN A TERTIARY CARE TEACHING HOSPITAL AT RIMS KADAPA

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Dr. T. Lakshmi Suseela*, Dr. S. Jaya Jyothi, Dr. P. Rabbani, Dr. Chb. Jhonsi.
Objective: To assess the effects of tranexamic acid among patients undergoing cesarean delivery who were at high risk of postpartum hemorrhage for Obstetrics and Gynaecology department in RIMS Kadapa. Methods: Between August 1, 2014, and April 30, 2015, a randomized controlled trial was performed at a tertiary care teaching hospital at kadapa. Women undergoing an elective or emergency cesarean delivery who were at high risk for postpartum hemorrhage were enrolled. They were randomly assigned using sealed, opaque envelopes to receive 10 mg/kg tranexamic acid or normal saline 10 min before skin incision. Anesthesiologists were not masked to group assignment, but patients and obstetricians were. The primary outcome was need for additional uterotonic drugs within 24 h after delivery. Analyses were by intention to treat. Results: Thirty patients were assigned to each group. Additional uterotonic drugs were required in 7 (23%) patients assigned to tranexamic acid and 25 (83%) patients in the control group (P

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DERCUM’S DISEASE: AN OVERVIEW OF CLASSIFICATION, CLINICALPRESENTATION, DIAGNOSTIC CRITERIA AND MANAGEMENT

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Ammu A, Babitha Annie Eapen, Jasmin Elizabeth Thomas, Merin Joseph, Apollo James, T Sivakumar.
Dercums disease is a rare disorder described by generalized obesity with painful adipose tissue. The clinical symptoms presented were multiple painful fatty masses, fatiguablity, swelling of fingers, morning stiffness, cognitive dysfunction, headache, anxiety, rapid heartbeat, shortness of breath, bloating, constipation, easy bruisability, joint aches, muscle aches, mood swing, delirium and dementia. Dercums disease affects women more frequently than men. Elevated erythrocyte sedimentation rate, alpha-1 antitrypsin, orosomucoid, haptoglobin, compliment factors C3.C4, Clq and Cls have been found in Dercums disease. Differential diagnosis includes Fibromyalgia, Madelungs, Familial multiple lipomatosis, Proteus syndrome, Weber-christian disease, Neurofibromatosis type1, Frohlich syndrome, Lipodystrophia andMetabolic disorders. The diagnosis is made clearly when the differential diagnoses have been excluded. The main goal of treatment in Dercums disease includes the pain reduction with surgical interventions (liposuction, excision), pharmacological therapies (analgesics, membrane stabilizing agents, corticosteroids, calcium channel modulators, methotrexate and infliximab, Interferon α-2b) and other alternative such as Rapid cycling hypobaric pressure and Frequency Modulated Electromagnetic Neural Stimulation. We propose a review on definition, classification, pathophysiology, diagnostic methods and treatment.


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A RARE CASE REPORT ON DRUGs’ ADVERSE REACTION ON SODIUM VALPROATE: UNUSUAL COMPLAINTS OF VERTIGO, DIZZINESS AND INCREASED SALIVATION

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Elizabeth Phoeba Paul*, Jasmin Elizabeth Thomas, Josna James, Geethu C, T Sivakumar.
Sodium Valproate usage in the field of medicine has been started earlier in the 1960s. Toxicity has been rising steadily nowadays and its signs and symptoms of include CNS abnormalities, respiratory depression, nausea or vomiting and abnormalities in laboratory investigations include elevated serum Sodium Valproate levels, hypernatremia, elevated anion gap metabolic acidosis, hyperosmolality, hypocalcemia, and hyperammonemia. At this juncture, we report a case with seizures who was given Sodium Valproate and was switched on to Phenytoin due to toxicity as the patient complained of unusual adverse drug reactions.


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AN OVERVIEW ON TRANSDERMAL DRUG DELIVERY

2016-08-09T05-51-53Z
Source: Indo American Journal of Pharmaceutical Research
Abhinay Chhetri*, Dr.Biplab Kumar Dey.
Transdermal drug delivery system is also known as a transdermal patch or skin patch which deliver a specific dose of medication to the systemic circulation. It is a medicated adhesive patch. Morphological, biophysical and physicochemical properties of the skin are to be considered when therapeutic agents are delivered through the human skin for systemic effects. Transdermal drug delivery system can improve the therapeutic efficacy and safety of the drugs because drug delivered through the skin at a predetermined and controlled rate. Skin is the important site of drug application for both the local and systemic effects. Characterization of transdermal patch is use to check its quality, size, time of onset & duration, adhesive property, thickness, weight of patch, moisture of content, uniformity & cutaneous toxicological studies. This review article provides an overview of TDDS, its advantages over conventional dosage forms, drug delivery routes across human skin, permeation enhancers, and various components of transdermal patches, types of transdermal patches, methods of preparation and its methods of evaluation.


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Eosinophilic esophageal myositis diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: a case report

Abstract

Eosinophilic esophagitis (EoE) is diagnosed by microscopic findings of eosinophilic infiltration into the squamous epithelium. In contrast, another disease concept termed "eosinophilic esophageal myositis (EoEM)" has been proposed, whereby there is eosinophilic infiltration into the muscularis propria instead. A 60-year-old man was referred to our hospital for chest pain, dysphagia, and several episodes of esophageal food impaction. Although EoE was suspected based on clinical features, biopsy specimens showed no mucosal eosinophilic infiltration. Endoscopic ultrasound (EUS) showed thickening of the muscularis propria layer and subsequent EUS-guided fine-needle aspiration biopsy (EUS-FNA) revealed eosinophilic infiltration into the muscularis propria. Although the patient's symptoms gradually improved after steroid administration, complete remission was not achieved after 1 year of treatment. This case may reflect a disorder distinct from typical EoE based on eosinophilic infiltration of the muscularis propria but not the squamous epithelium, and we, therefore, diagnosed it as EoEM using the EUS-FNA findings as reference.



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Dual red imaging (novel advanced endoscopy) can increase visibility and can predict the depth in diagnosing esophageal varices

Abstract

Background

Dual red imaging (DRI) is a new technology that can increase the visibility of deeper veins compared with narrow band imaging (NBI). As esophageal varices (EVs) are a vascular disease occurring in the submucosal layer, their visibility might be increased by DRI. We prospectively clarified whether the visibility of EVs with red color sign (RCS) can be increased by DRI, and clarified the relation between the visibility scores and the obtained endoscopic ultrasound (EUS) images.

Methods

Forty patients were enrolled. The visibility of the EVs on DRI and NBI endoscopic images was evaluated by five observers in a blinded manner and was compared with a white light image (bad, 0; equal, 1; good, 2). The diameter of the lumen and the depth of the EVs and RCS from the epithelium were measured by EUS. The relation between the visibility scores and the EUS findings was investigated.

Results

The DRI scores were 1.66 ± 0.34 for the EV substance and 1.79 ± 0.28 for the RCS, whereas the NBI scores were 0.68 ± 0.38 and 0.41 ± 0.28, respectively. A significant negative correlation was found between the depth and the visibility score (r = −0.505, p = 0.001 for EVs; r = −0.458, p = 0.003 for RCS).

Conclusions

DRI increased the visibility of the EVs and RCS. The visibility of the EVs or RCS in the shallower position was more enhanced by DRI. Visual recognition of the changing degrees of visibility by DRI enables the prediction of the depth of EVs.



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Biomechanics and Physiology of Uphill and Downhill Running

Abstract

Most running studies have considered level running (LR), yet the regulation of locomotor behaviour during uphill (UR) and downhill (DR) running is fundamental to increase our understanding of human locomotion. The purpose of this article was to review the existing literature regarding biomechanical, neuromuscular and physiological adaptations during graded running. Relative to LR, UR is characterized by a higher step frequency, increased internal mechanical work, shorter swing/aerial phase duration, and greater duty factor, while DR is characterized by increased aerial time, reduced step frequency and decreased duty factor. Grade also modifies foot strike patterns, with a progressive adoption of a mid- to fore-foot strike pattern during UR, and rear-foot strike patterns during DR. In UR, lower limb muscles perform a higher net mechanical work compared to LR and DR to increase the body's potential energy. In DR, energy dissipation is generally prevalent compared to energy generation. The increased demands for work as running incline increases are met by an increase in power output at all joints, particularly the hip. This implies that UR requires greater muscular activity compared to LR and DR. Energy cost of running (C r) linearly increases with positive slope but C r of DR decreases until a minimum slope is reached at −20 %, after which C r increases again. The effects of slope on biomechanics, muscle contraction patterns and physiological responses have important implications for injury prevention and success of athletes engaged in graded running competitions.



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A prospective randomized comparison of testicular functions, sexual functions and quality of life following laparoscopic totally extra-peritoneal (TEP) and trans-abdominal pre-peritoneal (TAPP) inguinal hernia repairs

Surgical Endoscopy

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Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: A prospective study

Journal of Hepatology

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Long-term glucocorticoid concentrations as a risk factor for childhood obesity and adverse body-fat distribution

International Journal of Obesity

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Systematic review and meta-analysis on the prevalence of vitamin D deficiency in patients with chronic pancreatitis

Pancreatology

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Usefulness of the short–echo time cube sequence at 3-T magnetic resonance cholangiopancreatography: Prospective comparison with the conventional 3-dimensional fast spin-echo sequence

Journal of Computer Assisted Tomography

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Ten-day empirical sequential or concomitant therapy is more effective than triple therapy for Helicobacter pylori eradication: A multicenter, prospective study

Digestive and Liver Diseases

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Risk factors for drainage-requiring ascites after refractory peritonitis in peritoneal dialysis patients

International Urology and Nephrology

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Epilepsy as a risk factor for hepatic encephalopathy in patients with cirrhosis: A cohort study

BMC Gastroenterology

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PGE2 signaling promotes the expansion of ALDH1-positive tumor cells in pancreatic ductal adenocarcinoma

Pancreatology

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Hepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15

Journal of Clinical Virology

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Outcomes of concomitant ventral hernia repair performed during bariatric surgery

Surgical Endoscopy

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Women’s Use of Health Care in the First 2 Years Postpartum: Occurrence and Correlates

Abstract

Objectives We sought to determine rates and correlates of accessing health care in the 2 years following delivery among women at an urban academic medical center. Methods We used electronic medical records, discharge, and billing data to determine the occurrence of primary care, other non-primary outpatient care, emergency department visits, and inpatient admissions among women delivering at a single medical center who had a known primary care affiliation to that medical center over a 5 year period. We explored sociodemographic, clinical, and health care-related factors as correlates of care, using bivariate and multivariable modeling. Results Of 6216 women studied, most (91 %) had had at least one health care visit in the window between 2 months and 2 years postpartum (the "late postpartum period"). The majority (81 %) had had a primary care visit. Factors associated with use of health care in this period included a chronic medical condition diagnosed prior to pregnancy (adjusted odds ratio (AOR) 1.42, 95 % CI [1.19, 1.71]), prenatal care received in an urban community health center (AOR 1.35 [1.06, 1.73]), having received obstetric (AOR 1.90 [1.51, 2.37]), primary (AOR 2.30 [1.68, 3.23]), or other non-primary outpatient care (AOR 2.35 [1.72, 3.39]) in the first 2 months postpartum, and living closer to the hospital [AOR for residence >17.8 miles from the medical center (AOR 0.74 [0.61, 0.90])]. Having had an obstetrical complication did not increase the likelihood of receipt of care during this window. Conclusions for Practice Among women already enrolled in a primary care practice at our medical center, health care utilization in the late postpartum period is high, but not universal. Understanding the characteristics of women who return for health care during this window, and where they are seen, can improve transitions of care across the life course and can provide opportunities for important and consistent interconception and well-woman messaging.



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Usefulness of mean corpuscular volume as a surrogate marker for monitoring thiopurine treatment in inflammatory bowel disease

European Journal of Gastroenterology & Hepatology

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Efficacy of transoral incisionless fundoplication (TIF) for the treatment of GERD: A systematic review with meta-analysis

Surgical Endoscopy

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Esophageal stent fixation with endoscopic suturing device improves clinical outcomes and reduces complications in patients with locally advanced esophageal cancer prior to neoadjuvant therapy: A large multicenter experience

Surgical Endoscopy

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Is salvage liver resection necessary for initially unresectable hepatocellular carcinoma patients downstaged by transarterial chemoembolization? ten years of experience

The Oncologist

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Preventing anastomotic complications: Early results of laparoscopic gastric devascularization two weeks prior to minimally invasive esophagectomy

Surgical Endoscopy

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A cross-sectional study on the perceptions and practices of teenagers with inflammatory bowel disease about repeated stool sampling

Journal of Adolescent Health

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Lower Extremity Stiffness Changes following Concussion in Collegiate Football Players.

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Purpose: Recent research indicates that a concussion increases risk of musculoskeletal injury. Neuromuscular changes following concussion might contribute to the increased risk of injury. Many studies have examined gait post-concussion, but few studies have examined more demanding tasks. This study compared changes in stiffness across the lower extremity, a measure of neuromuscular function, during a jump-landing task in athletes with a concussion (CONC) to uninjured athletes (UNINJ). Methods: Division I football players (13 CONC, 26 UNINJ) were tested pre- and post-season. A motion-capture system recorded subjects jumping on one limb from a 25.4 cm step onto a force plate. Hip, knee, and ankle joint stiffness were calculated from initial contact to peak joint flexion using the regression line slopes of the joint moment versus joint angle plots. Leg stiffness was (peak vertical ground reaction force (PVGRF)/lower extremity vertical displacement) from initial contact to PVGRF. All stiffness values were normalized to bodyweight. Values from both limbs were averaged. General linear models compared group (CONC, UNINJ) differences in the changes of pre- and post-season stiffness values. Results: Average time from concussion to post-season testing was 49.9 days. The CONC group showed an increase in hip stiffness (p=0.03), a decrease in knee (p=0.03) and leg stiffness (p=0.03), but no change in ankle stiffness (p=0.65) from pre- to post-season. Conclusion: Lower extremity stiffness is altered following concussion, which could contribute to an increased risk of lower extremity injury. These data provide further evidence of altered neuromuscular function after concussion. (C) 2016 American College of Sports Medicine

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High-Speed Cycling Intervention Improves Rate-Dependent Mobility in Older Adults.

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PURPOSE: The aim was to determine the feasibility of a six-week speed-based exercise program that could be used to initiate new exercise behaviors and improve rapid movement in older adults approaching frailty. METHODS: The intervention group included 14 older adults (3 males, 11 females, mean (SD) age: 70 (7.6) years, height: 1.6 (.11) m, mass: 76.8 (12.0) kg, BMI: 27.7(4.7)). The control group included 12 older adults (6 males, 6 females, mean (SD) age: 69.2 (6.9) years, height: 1.7 (.09) m, mass: 78.2 (10.9) kg, BMI: 25.3 (2.7)). Subjects included active older adults, including regular exercisers, but none were engaged in sports or exercises with an emphasis on speed (e.g. cycling spin classes or tennis). Stationary recumbent cycling was selected to minimize fall risk and low pedaling resistance reduced musculoskeletal and cardiovascular load. Two weekly 30-minute exercise sessions consisted of interval training in which subjects pedaled at preferred cadence and performed ten 20-s fast cadence intervals separated by 40-s of active recovery at preferred cadence. RESULTS: Significant Group by Time interactions (p<.05 supported a improvement in the timed up and go test rapid isometric knee extension contractions exercise group but not controls. central neural adaptations are suggested because this lower extremity program also elicited significant improvements untrained upper extremities of rfd-sf peg p conclusion: these results demonstrate that relatively low dose speed-based can improve neuromuscular function tests mobility older adults. such serves as sensible precursor to subsequent more vigorous training or an adjunct where velocity emphasis is lacking. american college sports medicine>

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The Impact of Age on the VO2max Response to High-Intensity Interval Training.

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Purpose: High-intensity interval training (HIIT) is documented to yield effective improvements in the cardiovascular system and be an excellent strategy for healthy aging. However, it is not determined how age may impact the training response of key components of aerobic endurance. Methods: We recruited 72 males (84.9+/-12.9 kg; 180.4+/-5.8cm) and 22 females (76.0+/-17.2 kg; 171.2+/-6.7cm) from 20-70+ years with a training status typical for their age group, and divided them into six decade-cohorts. The participants followed supervised training with a targeted intensity of 90-95% of maximal heart rate (HRmax) 3 x week for 8 weeks. Results: After HIIT, all age groups increased (p

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Potential Corticomotor Plasticity in those with and without Chronic Ankle Instability.

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Introduction: Quantifying corticomotor alterations is important to understand the neurophysiological mechanisms that likely contribute to the neuromuscular control deficits observed in patients with Chronic Ankle Instability (CAI). Corticomotor output mapping provides further insight into the changes within the motor cortex and identifies potential changes in the area of the motor cortex associated with selected muscles. Therefore, this investigation compared the corticomotor map output for the fibularis longus(FL) muscle in patients with and without CAI. Methods: Eighteen CAI patients and 16 Healthy-controls(HC) volunteered. Transcranial Magnetic Stimulation was used to map the motor cortex's representation of the FL. The normalized average of three motor evoked potentials(MEP) at 100% of Active Motor Threshold(AMT) intensity was recorded for each scalp site on a 6x6 cm grid. Corticomotor output map was compared between groups through 1) size of the corticomotor map area, 2) volume of the corticomotor map and 3) the location of cortical representation (LCR). Independent T-tests were used to assess group differences in each mapping outcome variable. Cohen's d effect sizes along with 95% confidence intervals (CI) were calculated using the pooled standard deviations. Results: CAI patients exhibited less map volume (p=0.018, CAI: 8.2+/-3.2 cm2 mV vs. HC: 11.3 +/- 3.9 cm2 mV) and map area (p=0.046, CAI: 12.8+/-6.0 cm2 vs. HC: 17.4+/-6.9 cm2) compared to HC. Conclusions: The smaller map area and volume suggest a more concentrated area of neurons communicating with the FL muscle in patients with CAI. Consequently, motor cortical cells on the border of the FL excitation area are less committed to the proper function of the FL muscle and may be recruited by other surrounding areas. This may explain altered movement strategies that lead to ankle re-injury. (C) 2016 American College of Sports Medicine

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Effects of Energy Shots on Blood Pressure in Caffeine-Naive Versus Caffeine-Consuming Healthy Volunteers

Journal of Caffeine Research , Vol. 0, No. 0.


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