Δευτέρα, 4 Ιουλίου 2016

Effects of age and non-oropharyngeal proprioceptive and exteroceptive sensation on the magnitude of anticipatory mouth opening during eating

Summary

To best prevent and treat eating/swallowing problems, it is essential to understand how components of oral physiology contribute to the preservation and/or degradation of eating/swallowing in healthy ageing. Anticipatory, pre-swallow motor movements may be critical to safe and efficient eating/swallowing, particularly for older adults. However, the nature of these responses is relatively unknown. This study compared the magnitude of anticipatory mouth opening during eating in healthy older (aged 70–85) and younger (aged 18–30) adults under four eating conditions: typical self-feeding, typical assisted feeding (being fed by a research assistant resulting in proprioceptive loss), sensory loss self-feeding (wearing blindfold/headphones resulting in exteroceptive loss) and sensory loss assisted feeding (proprioceptive and exteroceptive loss). Older adults opened their mouths wider than younger adults in anticipation of food intake under both typical and most non-oropharyngeal sensory loss conditions. Further, the loss of proprioceptive and exteroceptive cues resulted in decreased anticipatory mouth opening for all participants. Greater mouth opening in older adults may be a protective compensation, contributing to the preservation of function associated with healthy ageing. Our finding that the loss of non-oropharyngeal sensory cues resulted in decreased anticipatory mouth opening highlights how important proprioception, vision, and hearing are in pre-swallow behaviour. Age- and disease-related changes in vision, hearing, and the ability to self-feed may reduce the effectiveness of these pre-swallow strategies.



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A comparative study of terrestrial gamma dose rate in air measured by thermoluminescent dosimeter, portable survey meter and HPGe gamma spectrometer

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Publication date: November 2016
Source:Journal of Environmental Radioactivity, Volume 164
Author(s): Yan-Jun Huang, Gui-Yin Guo, Yi He, Li-Tao Yang, Zhen Shan, Chao-Feng Chen, Zhi-Hong Shang-Guan
In this paper, three different widely-used measurement techniques for environmental gamma dose rate were studied and compared, i.e., the thermoluminescent dosimeter, the portable survey meter and the spectrometric analysis. Thirteen investigation sites were selected, and the TLDs were arranged to accumulate the radiation signals during an interval of about one quarter, the instant dose rates by using a portable survey meter were collected around the site, and top surface soils were sampled in the surroundings for radionuclides analyzing in laboratory. The results from these methods were compared, which revealed high correlations. The differences and possible uncertainties for the three methods were analyzed, inspired a further study should be conducted to have more successful estimation of dose rate in surface air.



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Development of a rapid on-site inspection radioxenon processing system and its applications during IFE14 and related activities

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Publication date: October 2016
Source:Journal of Environmental Radioactivity, Volumes 162–163
Author(s): Chongyang Zhou, Guoqing Zhou, Shujuan Feng, Dingwei Huang, Xinhua Zhao, Elisabeth Wieslander, Kirill Khrustalev, Xiaolong Yu, Ziwei Cheng, Rui Wu, Ronghu Zou
To take part in the Integrated Field Exercise in 2014 (IFE14) in Jordan, a rapid on-site inspection radioxenon processing system (XESPM-III) has been developed to monitor radioxenon isotopes (131m,133,133m,135Xe), mainly in subsoil gas. XESPM-III is composed of sampling, purification, and measurement units. The function of the sampling unit is to pre-enrich xenon after the removal of impurities, while the purification unit purifies and separates impurities and prepares a small-volume relatively high concentration of xenon gas as a measuring sample; the purpose of the measurement unit is to analyze stable xenon and measure the radioxenon activity. The parameters used for operation of XESPM-III are as follows: sampling volume, 4 m3 or 2 m3 + 2 m3; daily throughput, 12 × (2 m3) or 6 × (4 m3); volume of gas measuring sample, approximately 7 cm3; recovery, >70%; radon removal coefficient, 10−6; cross contamination, <1%; 133Xe minimum detectable activity concentration, 11 × (2 m3) and 5 × (4 m3) mBq/m3 or 1.4 × (2 m3) and 0.7 × (4 m3) mBq/m3 if measured by HPGe γ spectrometry or a β-γ coincidence counting system using an acquisition time of 40,000 s, respectively. XESPM-III was able to detect 133Xe in subsoil gas during IFE14.



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Ecological effects of exposure to enhanced levels of ionizing radiation

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Publication date: October 2016
Source:Journal of Environmental Radioactivity, Volumes 162–163
Author(s): Stanislav A. Geras'kin
Irradiation of plants and animals can result in disruption of ecological relationships between the components of ecosystems. Such effects may act as triggers of perturbation and lead to consequences that may differ essentially from expected ones based on effects observed at the organismal level. Considerable differences in ecology and niches occupied by different species lead to substantial differences in doses of ionizing radiation absorbed by species, even when they all are present in the same environment at the same time. This is especially evident for contamination with α-emitting radionuclides. Radioactive contamination can be considered an ecological factor that is able to modify the resistance in natural populations. However, there are radioecological situations when elevated radioresistance does not evolve or persist. The complexity and non-linearity of the structure and functioning of ecosystems can lead to unexpected consequences of stress effects, which would appear harmless if they were assessed within the narrower context of organism-based traditional radioecology. Therefore, the use of ecological knowledge is essential for understanding responses of populations and ecosystems to radiation exposure. Integration of basic ecological principles in the design and implementation of radioecological research is essential for predicting radiation effects under rapidly changing environmental conditions.



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Inverse modeling of the 137Cs source term of the Fukushima Dai-ichi Nuclear Power Plant accident constrained by a deposition map monitored by aircraft

Publication date: November 2016
Source:Journal of Environmental Radioactivity, Volume 164
Author(s): Keiya Yumimoto, Yu Morino, Toshimasa Ohara, Yasuji Oura, Mitsuru Ebihara, Haruo Tsuruta, Teruyuki Nakajima
The amount of 137Cs released by the Fukushima Dai-ichi Nuclear Power Plant accident of 11 March 2011 was inversely estimated by integrating an atmospheric dispersion model, an a priori source term, and map of deposition recorded by aircraft. An a posteriori source term refined finer (hourly) variations comparing with the a priori term, and estimated 137Cs released 11 March to 2 April to be 8.12 PBq. Although time series of the a posteriori source term was generally similar to those of the a priori source term, notable modifications were found in the periods when the a posteriori source term was well-constrained by the observations. Spatial pattern of 137Cs deposition with the a posteriori source term showed better agreement with the 137Cs deposition monitored by aircraft. The a posteriori source term increased 137Cs deposition in the Naka-dori region (the central part of Fukushima Prefecture) by 32.9%, and considerably improved the underestimated a priori 137Cs deposition. Observed values of deposition measured at 16 stations and surface atmospheric concentrations collected on a filter tape of suspended particulate matter were used for validation of the a posteriori results. A great improvement was found in surface atmospheric concentration on 15 March; the a posteriori source term reduced root mean square error, normalized mean error, and normalized mean bias by 13.4, 22.3, and 92.0% for the hourly values, respectively. However, limited improvements were observed in some periods and areas due to the difficulty in simulating accurate wind fields and the lack of the observational constraints.

Graphical abstract

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Identifiability of sorption parameters in stirred flow-through reactor experiments and their identification with a Bayesian approach

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Publication date: October 2016
Source:Journal of Environmental Radioactivity, Volumes 162–163
Author(s): V. Nicoulaud-Gouin, L. Garcia-Sanchez, M. Giacalone, J.C. Attard, A. Martin-Garin, F.Y. Bois
This paper addresses the methodological conditions –particularly experimental design and statistical inference– ensuring the identifiability of sorption parameters from breakthrough curves measured during stirred flow-through reactor experiments also known as continuous flow stirred-tank reactor (CSTR) experiments. The equilibrium-kinetic (EK) sorption model was selected as nonequilibrium parameterization embedding the Kd approach. Parameter identifiability was studied formally on the equations governing outlet concentrations. It was also studied numerically on 6 simulated CSTR experiments on a soil with known equilibrium-kinetic sorption parameters. EK sorption parameters can not be identified from a single breakthrough curve of a CSTR experiment, because Kd,1 and k were diagnosed collinear. For pairs of CSTR experiments, Bayesian inference allowed to select the correct models of sorption and error among sorption alternatives. Bayesian inference was conducted with SAMCAT software (Sensitivity Analysis and Markov Chain simulations Applied to Transfer models) which launched the simulations through the embedded simulation engine GNU-MCSim, and automated their configuration and post-processing. Experimental designs consisting in varying flow rates between experiments reaching equilibrium at contamination stage were found optimal, because they simultaneously gave accurate sorption parameters and predictions. Bayesian results were comparable to maximum likehood method but they avoided convergence problems, the marginal likelihood allowed to compare all models, and credible interval gave directly the uncertainty of sorption parameters θ. Although these findings are limited to the specific conditions studied here, in particular the considered sorption model, the chosen parameter values and error structure, they help in the conception and analysis of future CSTR experiments with radionuclides whose kinetic behaviour is suspected.



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Long-term measurements of residential radon, thoron, and thoron progeny concentrations around the Chhatrapur placer deposit, a high background radiation area in Odisha, India

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Publication date: October 2016
Source:Journal of Environmental Radioactivity, Volumes 162–163
Author(s): Yasutaka Omori, Ganesh Prasad, Atsuyuki Sorimachi, Sarata Kumar Sahoo, Tetsuo Ishikawa, Devulapalli Vidya Sagar, Rakesh Chand Ramola, Shinji Tokonami
The Chhatrapur placer deposit is found in a high background radiation area which has been recently identified on the southeastern coast of India. Previously, some geochemical studies of this area were carried out to assess external dose from radionuclides-bearing heavy mineral sands. In this study, radon, thoron and thoron progeny concentrations were measured in about 100 dwellings during three seasons (autumn-winter, summer, and rainy) in a 10- to 12-month period and annual doses due to inhalation of them were evaluated. The measurements were made by passive-type radon-thoron discriminative detectors and thoron progeny detectors in which solid state nuclear track detectors were deployed. The results show that radon and thoron concentrations differ by one order of magnitude depending on exposure periods, while thoron progeny concentration is nearly constant throughout the year. Since thorium-rich sand is distributed in the studied area, exposure to thoron is equal to, or exceeds, exposure to radon and is not negligible for dose evaluation. Based on the measurements, doses due to inhalation of radon and thoron are evaluated as 0.1–1.6 mSv y−1 and 0.2–3.8 mSv y−1, respectively. The total dose is 0.8–4.6 mSv y−1, which is the same order of magnitude as the worldwide value.



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Disparate radiocesium leaching from two woody species by acceleration of litter decomposition using microbial inoculation

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Publication date: October 2016
Source:Journal of Environmental Radioactivity, Volumes 162–163
Author(s): Shin-nosuke Hashida, Toshihiro Yoshihara
Studies focusing on the migration of radionuclides in the forest floor have demonstrated that the ecological half-life of radiocesium on organic layer containing the debris of plant litter with various fungi and microorganisms is shorter than that in the deeper soil zone, suggesting that the litter decomposition affects radiocesium mobilization. Here, we showed the involvement of lignin, one of the major cell wall components of plant litter, in the fate of contaminated radiocesium during the process of fungal litter decomposition. In this study, litter decomposition of two different woody species, broadleaf deciduous Japanese cherry consisted of hardwood lignin and coniferous evergreen Japanese cedar with softwood lignin, were accelerated by in vitro fungal inoculation. In vitro inoculation exhibited 1.93- to 2.59-times faster decomposition than field experiment. Then, the cherry litter lost approximately 25% of initially contaminated radiocesium within 1 month of in vitro decomposition, whereas the cedar litter kept initial level at least for 6 month. The retention of radiocesium correlated with thioglycolate lignin content in cedar litter but not in cherry litter. Consequently, the behavior of radiocesium contaminated in litter fall may vary depending on the contamination pathway or the manner of nutrient mobilization at the stage of abscission between evergreen and deciduous trees.



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Cosmic-muon intensity measurement and overburden estimation in a building at surface level and in an underground facility using two BC408 scintillation detectors coincidence counting system

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Publication date: October 2016
Source:Journal of Environmental Radioactivity, Volumes 162–163
Author(s): Weihua Zhang, Kurt Ungar, Chuanlei Liu, Maverick Mailhot
A series of measurements have been recently conducted to determine the cosmic-muon intensities and attenuation factors at various indoor and underground locations for a gamma spectrometer. For this purpose, a digital coincidence spectrometer was developed by using two BC408 plastic scintillation detectors and an XIA LLC Digital Gamma Finder (DGF)/Pixie-4 software and card package. The results indicate that the overburden in the building at surface level absorbs a large part of cosmic ray protons while attenuating the cosmic-muon intensity by 20–50%. The underground facility has the largest overburden of 39 m water equivalent, where the cosmic-muon intensity is reduced by a factor of 6. The study provides a cosmic-muon intensity measurement and overburden assessment, which are important parameters for analysing the background of an HPGe counting system, or for comparing the background of similar systems.



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Fundamental uncertainty equations for nuclear dating applied to the 140Ba-140La and 227Th-223Ra chronometers

Publication date: October 2016
Source:Journal of Environmental Radioactivity, Volumes 162–163
Author(s): S. Pommé, S.M. Collins, A. Harms, S.M. Jerome
Basic equations for age dating through activity ratio measurements are presented and applied to nuclear chronometers based on parent-daughter decay. Uncertainty propagation formulae are derived which relate the relative uncertainty on the half-lives and measured activity ratios with the relative uncertainty on the calculated time of a nuclear event. Particular attention is paid to the case of relatively short-lived radionuclides for which the change in decay rate during the measurement is non-negligible. Mathematical solutions are presented to correct the perceived activity ratio and adapt the uncertainty propagation formulae to complete the uncertainty budget. The formulae have been applied to 140Ba-140La chronometry, which is particularly useful for dating a nuclear explosion through measurement of the produced activity ratio of 140La and 140Ba in a finite time interval. They were also applied to the 227Th-223Ra parent-daughter pair produced for therapeutic use. The impact of inaccuracies in the nuclear decay data on the performance of these nuclear chronometers is shown and discussed.



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Measurements of cesium in Arctic beluga and caribou before and after the Fukushima accident of 2011

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Publication date: October 2016
Source:Journal of Environmental Radioactivity, Volumes 162–163
Author(s): T.J. Stocki, M. Gamberg, L. Loseto, E. Pellerin, L. Bergman, J.-F. Mercier, L. Genovesi, M. Cooke, B. Todd, D. Sandles, J. Whyte, X. Wang
Concern from northern communities following the Fukushima Daiichi nuclear accident of March 2011 has prompted a reassessment of the safety of their traditional foods with respect to radioactivity levels. To this end, a study was conducted to measure the levels of radionuclides in Arctic caribou (Rangifer tarandus) and beluga (Delphinapterus leucas). The main radionuclide of concern is cesium-137, which is easily transferred through the lichen-caribou food chain. Previous studies have been conducted on the cesium-137 levels in Canadian caribou herds from 1958 to 2000, allowing researchers to determine the amount of cesium-137 in caribou specifically attributable to atmospheric weapons testing and the Chernobyl nuclear accident in 1986. In this study, samples of lichens, mushrooms, caribou, beluga and beluga prey collected before and after the Fukushima accident were analyzed for radioactivity levels. Samples were processed and measured using gamma ray spectroscopy to identify the radionuclides present and determine the radioactivity concentration. Both calibration standards and Monte Carlo simulations were used to determine the efficiency of the detectors for the samples, taking into account differences in individual sample sizes as well as matrices. In particular, a careful analysis of the atomic composition of lichens and mushrooms was performed to ensure the efficiencies for these sample types were correct. A comparison of the concentrations from before and after the accident indicated that there was no increase in radioactivity as a result of the atmospheric plume from the Fukushima accident. Some cesium-137, likely attributable to fallout from atmospheric weapons testing of the 1950s and 1960s (since there was no cesium-134 measured in the samples), was measured in the post Fukushima caribou and beluga whale samples; however, this amount was determined to be insignificant for any radiological concern (9.1 ± 1.8 and 0.63 ± 0.23 Bq kg−1 ww respectively). The activity concentrations of cesium-137 was about 200 times smaller than that of natural radioactive potassium in the beluga samples. Both the caribou and beluga results showed that these foods continue to be a healthy food choice for northern Canadians with respect to radioactivity, and this result has been communicated to the nearby northern communities and stakeholders.



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ApoA-I induces S1P release from endothelial cells through ABCA1 and SR-BI in a positive feedback manner

Abstract

Sphingosine-1-phosphate (S1P), which has emerged as a pivotal signaling mediator that participates in the regulation of multiple cellular processes, is derived from various cells, including vascular endothelial cells. S1P accumulates in lipoproteins, especially HDL, and the majority of free plasma S1P is bound to HDL. We hypothesized that HDL-associated S1P is released through mechanisms associated with the HDL maturation process. ApoA-I, a major HDL apolipoprotein, is a critical factor for nascent HDL formation and lipid trafficking via ABCA1. Moreover, apoA-I is capable of promoting bidirectional lipid movement through SR-BI. In the present study, we confirmed that apoA-I can facilitate the production and release of S1P by HUVECs. Furthermore, we demonstrated that ERK1/2 and SphK activation induced by apoA-I is involved in the release of S1P from HUVECs. Inhibitor and siRNA experiments showed that ABCA1 and SR-BI are required for S1P release and ERK1/2 phosphorylation induced by apoA-I. However, the effects triggered by apoA-I were not suppressed by inhibiting ABCA1/JAK2 or the SR-BI/Src pathway. S1P released due to apoA-I activation can stimulate the (ERK1/2)/SphK1 pathway through S1PR (S1P receptor) 1/3. These results indicated that apoA-I not only promotes S1P release through ABCA1 and SR-BI but also indirectly activates the (ERK1/2)/SphK1 pathway by releasing S1P to trigger their receptors. In conclusion, we suggest that release of S1P induced by apoA-I from endothelial cells through ABCA1 and SR-BI is a self-positive-feedback process: apoA-I-(ABCA1 and SR-BI)-(S1P release)-S1PR-ERK1/2-SphK1-(S1P production)-(more S1P release induced by apoA-I).



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Estimated Prestroke Peak VO2 Is Related to Circulating IGF-1 Levels During Acute Stroke

Background. Insulin-like growth factor-1 (IGF-1) is neuroprotective after stroke and is regulated by insulin-like binding protein-3 (IGFBP-3). In healthy individuals, exercise and improved aerobic fitness (peak oxygen uptake; peak VO2) increases IGF-1 in circulation. Understanding the relationship between estimated prestroke aerobic fitness and IGF-1 and IGFBP-3 after stroke may provide insight into the benefits of exercise and aerobic fitness on stroke recovery. Objective. The purpose of this study was to determine the relationship of IGF-1 and IGFBP-3 to estimated prestroke peak VO2 in individuals with acute stroke. We hypothesized that (1) estimated prestroke peak VO2 would be related to IGF-1 and IGFBP-3 and (2) individuals with higher than median IGF-1 levels will have higher estimated prestroke peak VO2 compared to those with lower than median levels. Methods. Fifteen individuals with acute stroke had blood sampled within 72 hours of hospital admission. Prestroke peak VO2 was estimated using a nonexercise prediction equation. IGF-1 and IGFBP-3 levels were quantified using enzyme-linked immunoassay. Results. Estimated prestroke peak VO2 was significantly related to circulating IGF-1 levels (r = .60; P = .02) but not IGFBP-3. Individuals with higher than median IGF-1 (117.9 ng/mL) had significantly better estimated aerobic fitness (32.4 ± 6.9 mL kg–1 min–1) than those with lower than median IGF-1 (20.7 ± 7.8 mL kg–1 min–1; P = .03). Conclusions. Improving aerobic fitness prior to stroke may be beneficial by increasing baseline IGF-1 levels. These results set the groundwork for future clinical trials to determine whether high IGF-1 and aerobic fitness are beneficial to stroke recovery by providing neuroprotection and improving function.



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The Effect of Propulsion Style on Wrist Movement Variability during the Push Phase after a Bout of Fatiguing Propulsion

Wheelchair propulsion has been linked to overuse injuries regardless of propulsion style. Many aspects of the arcing (ARC) and semicircular (SEMI) propulsion styles have been compared, but differences in intracycle movement variability, which have been linked to overuse injuries, have not been examined.

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The effect of current low back pain on volitional preemptive abdominal activation during a loaded forward reach activity

A volitional preemptive abdominal contraction (VPAC) supports trunk stability during functional activity. Pain-free individuals can sustain VPAC during function, but such has not been reported for individuals with current low back pain (cLBP).

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Graph Analysis of EEG Resting State Functional Networks in Dyslexic Readers

Reading involves integrated functioning of complex brain networks. Distinct brain systems, mostly in the left hemisphere, have been proposed to specialize during reading acquisition (see a review in Schlaggar and McCandliss, 2007). Studies in developmental dyslexia revealed various disturbances of the brain networks implicated in reading. Studies using diffusion tensor imaging (DTI) to examine white matter properties of the main pathways that constitute the anatomical basis of the network reported reduced connectivity in dyslexia (for a review and meta-analysis Vandermosten et al., 2012).

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From current status to optimization of HCV treatment: Recommendations from an expert panel

Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens.

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Basal values and changes of liver stiffness predict the risk of disease progression in compensated advanced chronic liver disease

Transient elastography has been proposed as a tool to predict the risk of decompensation in patients with chronic liver disease. We aimed to identify risk groups of disease progression, using a combination of baseline liver stiffness measurement (LSM) and its change over time (delta-LSM) in patients with compensated advanced chronic liver disease (cACLD).

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From current status to optimization of HCV treatment: Recommendations from an expert panel

Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens.

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Basal values and changes of liver stiffness predict the risk of disease progression in compensated advanced chronic liver disease

Transient elastography has been proposed as a tool to predict the risk of decompensation in patients with chronic liver disease. We aimed to identify risk groups of disease progression, using a combination of baseline liver stiffness measurement (LSM) and its change over time (delta-LSM) in patients with compensated advanced chronic liver disease (cACLD).

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Effects of improved fat meat products consumption on emergent cardiovascular disease markers of male volunteers at cardiovascular risk

Abstract

High meat-product consumption has been related to cardiovascular disease (CVD). However, previous results suggest the benefits of consuming improved fat meat products on lipoprotein-cholesterol and anthropometric measurements. Present study aims to assess the effect of consuming different Pâté and Frankfurter formulations on emergent CVD biomarkers in male volunteers at increased CVD risk. Eighteen male volunteers with at least two CVD risk factors were enrolled in a sequentially controlled study where different pork-products were tested: reduced-fat (RF), omega-3-enriched-RF (n-3RF), and normal-fat (NF). Pork-products were consumed during 4-week periods separated by 4-week washout. The cardiometabolic index (CI), oxidized low density lipoproteins (oxLDL), apolipoproteins (Apo) A1 and B, homocysteine (tHcys), arylesterase (AE), C-reactive Protein (CRP), tumor necrotic factor-alpha (TNFα), and lipoprotein (a) (Lp(a)) were tested and some other related ratios calculated. AE, oxLDL and Lp(a), AE/HDLc, LDLc/Apo B, and AE/oxLDL rate of change were differently affected (P<0.01) by pork-products consumption. RF increased (P < 0.05) AE, AE/HDLc and AE/oxLDL ratios and decreased TNFα, tHcys; n-3RF increased (P < 0.001) AE, AE/HDLc and AE/oxLDL ratios and decreased (P < 0.05) Lp(a); while NF increased (P<0.05) oxLDL and Lp(a) levels. In conclusion, RF and n-3RF products affected positively the level of some emergent CVD markers. The high regular consumption of NF-products should be limited as significantly increased Lp(a) and oxLDL values. The high variability in response observed for some markers suggests the need to perform more studies to identify targets for RF- and n-3RF-products.

Graphical Abstract

Emergent CVD markers


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Frequency of Cyp2c93* allele in patients with type 2 diabetes mellitus on sulfonylurea therapy

2016-07-04T10-09-58Z
Source: International Journal of Medical Science and Public Health
Prasanta Kumar Bhattacharya, Bornali Dutta, Aakash Roy.
Background: Sulfonylureas are mainstay of pharmacotherapy for type 2 diabetes mellitus (T2DM). Individual variability exists in pharmacokinetic and pharmacodynamic responses adverse effects to sulfonylurea. Objective: To determine frequency of cytochrome P450 2C9 mutant allele CYP2C93*, in T2DM patients on sulfonylurea therapy, and to ascertain the frequency of adverse drug reactions (ADR) with respect to particular allelic distribution. Materials and Methods: A hospital-based prospective observational study was carried out in a tertiary-care teaching hospital. Study included 136 T2DM patients on sulfonylurea therapy (83 with ≥1 ADR and 53 without ADR). DNA was isolated from the blood samples taken from all 136 patients by DNA isolation. PCR-RFLP (restriction fragment length polymorphism) technique was used for detection of CYP2C93* (Ile359Leu) allele and the wild type allele CYP2C91* by digestion with restriction enzyme. Data were analyzed using Statistical Package for Social Survey (SPSS) for Windows, version 16.0 and Microsoft Excel to determine descriptive statistics. Result: Allele CYP2C93* was detected in 11 patients. All alleles negative for the nucleotide substitutions at position 42614 (*3) were presumed to be wild type CYP2C9*1. Among the patients with CYP2C93* allele 11 patients experienced hypoglycemia and one patient experienced acute visual disturbances. No CYP2C93* was detected in the subjects without ADR. Conclusion: In our study CYP2C93* was identified in 11 patients experiencing hypoglycaemia and in one patient experiencing acute visual disturbances. In view of the existence of such polymorphisms and its effects on sulfonylurea therapy further studies are required to assess the magnitude of such problems in T2DM.


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Whole-genome sequencing in French Canadians from Quebec

Abstract

Genome-wide association studies (GWAS) have had a tremendous success in the identification of common DNA sequence variants associated with complex human diseases and traits. However, because of their design, GWAS are largely inappropriate to characterize the role of rare and low-frequency DNA variants on human phenotypic variation. Rarer genetic variation is geographically more restricted, supporting the need for local whole-genome sequencing (WGS) efforts to study these variants in specific populations. Here, we present the first large-scale low-pass WGS of the French-Canadian population. Specifically, we sequenced at ~5.6× coverage the whole genome of 1970 French Canadians recruited by the Montreal Heart Institute Biobank and identified 29 million bi-allelic variants (51 % novel), including 19 million variants with a minor allele frequency (MAF) <0.5 %. Genotypes from the WGS data are highly concordant with genotypes obtained by exome array on the same individuals (99.8 %), even when restricting this analysis to rare variants (MAF <0.5, 99.9 %) or heterozygous sites (98.9 %). To further validate our data set, we showed that we can effectively use it to replicate several genetic associations with myocardial infarction risk and blood lipid levels. Furthermore, we analyze the utility of our WGS data set to generate a French-Canadian-specific imputation reference panel and to infer population structure in the Province of Quebec. Our results illustrate the value of low-pass WGS to study the genetics of human diseases in the founder French-Canadian population.



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Awareness about sexually transmitted diseases among adolescents in urban slums of Jorhat district

2016-07-04T08-12-08Z
Source: International Journal of Medical Science and Public Health
Anuja Baruah, Bishnu Ram Das, Abu Hasan Sarkar.
Background: Adolescence is a vulnerable period for sexually transmitted diseases (STDs) because of curiosity, peer pressure, and lack of awareness. Objective: To assess the awareness regarding STDs in adolescents of urban slums of Jorhat district. Material and Methods: Community-based cross sectional study where 261 adolescents were interviewed using a predesigned, pre-tested proforma. Results: Among 261 adolescents, 74.7% had knowledge about STDs. Maximum awareness was seen in adolescents who were students (84.6%) and also in those belonging to the upper lower socio-economic class (87.5%). Most of the adolescents (48.3%) knew urethral discharge as a symptom of STD. Briefly, 55.17% adolescents felt that STDs can be prevented by the use of condom. Interestingly, 77% of the respondents felt that they should know more about STD and should be taught about STDs in school. Television (66.7%) was the most common source of information on STDs followed by friends (57.5%), newspaper (25.5%), and other means (17%). Conclusion: Correct scientific information should be disseminated to adolescent in both formal and informal settings so that they do not develop misconceptions. More awareness should be disseminated at schools, through mass media and a more friendly relationship is needed from parents.


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Effect of maternal antenatal influenza vaccination on adverse neonatal outcomes in terms of premature birth, small-for-gestational age and low birth weight: A comparative study

2016-07-04T08-12-08Z
Source: International Journal of Medical Science and Public Health
Mokhtar Mahfouz Shatla, Mohammed Essam Khayat, Majd Masoud Ahmed, Aamer Ali Alzahrani, Aymen Abdulrzag Khadrawi, Abdulrahman Saleh Almisfer, Shamsuldin Jamaluddin Zawawi, Abdulaziz Fouad Miyajan.
Background: Maternal influenza infection can impose significant health risks to pregnant women and their neonates. Objective: The objective of this study was to assess the effect of maternal antenatal influenza vaccination on adverse neonatal outcomes in terms of premature birth, small-for-gestational age (SGA), and low birth weight (LBW). Material and Methods: The present cross-sectional retrospective study included women who gave birth to their live third trimester neonates at a secondary care hospital in Saudi Arabia after exposure to the 2013/2014 influenza season in any entire trimester of their pregnancy. Neonatal outcomes of women who received inactivated influenza vaccine in their first, second, or early third trimester have been compared to the neonates of women who did not receive the vaccine throughout pregnancy. Data were collected by chart review. Results: In the present study, 1237 women were included, of these 347 (28.05%) received the trivalent inactivated influenza vaccine during pregnancy. Neonates born to vaccinated mothers were, on average, 97 g heavier (3279.7934 ± 337.6 compared with 3182.5107 ± 424.06, P = 0.001). Adverse neonatal outcomes were significantly lower in the vaccinated group; premature (9.1% compared with 17.6%, P = 0.001), SGA (8% compared with 14%, P = 0.003), and LBW (6.3% compared with 10.4%, P = 0.022). There was no significant increase in birth defects (2.2% compared to 2.6%, P = 0.711). Logistic regression analysis revealed that, compared to the neonates of mothers who received the vaccine, neonates of unvaccinated mothers are at almost two-fold increased risk of being premature (OR = 1.957; 95% CI, 1.3102.923; P = 0.001), 40% risk for SGA (OR = 1.409; 95% CI, 0.8722.275; P = 0.161), and 30% risk for LBW (OR = 1.306; 95% CI, 0.7732.206; P = 0.319). Conclusion: Maternal antenatal influenza vaccination is associated with reduced adverse neonatal outcomes in terms of premature birth, SGA, and LBW. Moreover, it is associated with having heavier babies, and not associated with increased birth defects.


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Sarcopenia in critically ill patients

Abstract

Sarcopenia occurring as a primary consequence of aging and secondary due to certain medical problems including chronic disease, malnutrition and inactivity is a progressive generalized loss of skeletal muscle mass, strength and function. The prevalence of sarcopenia increases with aging (approximately 5–13 % in the sixth and seventh decades). However, data showing the prevalence and clinical outcomes of sarcopenia in intensive care units (ICUs) are limited. A similar condition to sarcopenia in the ICU, called ICU-acquired weakness (ICU-AW), has been reported more frequently. Here, we aim to examine the importance of sarcopenia, especially ICU-AW, in ICU patients via related articles in Medline.



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The life aquatic: advances in marine vertebrate genomics

Nature Reviews Genetics. doi:10.1038/nrg.2016.66

Authors: Joanna L. Kelley, Anthony P. Brown, Nina Overgaard Therkildsen & Andrew D. Foote



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Computational genomics tools for dissecting tumour–immune cell interactions

Nature Reviews Genetics. doi:10.1038/nrg.2016.67

Authors: Hubert Hackl, Pornpimol Charoentong, Francesca Finotello & Zlatko Trajanoski



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Pattern of adverse drug reactions reported at a tertiary health care teaching hospital of Tripura: a retrospective study

2016-07-04T04-14-50Z
Source: International Journal of Basic & Clinical Pharmacology
Prithul Bhattacharjee, Lakshman Das, Ranjib Ghosh, Lalromawii, Uttam Kumar Das.
Background: ADR monitoring and reporting activity is in its infancy in India. India rates below 1% in pharmacovigilance as against the world rate of 5%. India is the fourth largest producer of pharmaceuticals in the world. So there is an immense need to improve the pharmacovigilance system to protect the Indian population. This study is aimed to identify ADRs and assess their pattern. Methods: The reports of ADRs were recorded as per the standard guidelines fixed by pharmacovigilance programme of India (PvPI). Naranjo ADR probability scale was used to assess the causality of suspected ADRs. Severity of ADRs was identified using modified hartwig's criteria. Types of ADRs were identified using Rawlins and Thompson classification. Results: A total 266 ADRs were reported from 190 patients. Majority of the ADRs were type A reactions. Highest incidence (78.95%) of ADRs was observed between 12-59 years of age. 56.84% of patients were male and 43.16% were female. Majority of the patients were suffering from single disease and receiving less than six medications. In the assessment of severity mild, moderate and severe ADRs were 57.89%, 35.26% and 6.84% respectively. In causality assessment 3.16% cases were unlikely, 57.37% cases were possible, 38.95% cases were probable and 0.52% cases were certain. Conclusions: The present study shows ADRs are commonly encountered at this tertiary health care set up. Many ADRs are life threatening type B reactions, but the higher incidence of type A reactions means that these can be avoided.


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Evaluation of anticonvulsant activity of volatile oil extract of Nigella sativa seeds by chemically induced seizure model in albino rats

2016-07-04T04-14-50Z
Source: International Journal of Basic & Clinical Pharmacology
Asmatanzeem Bepari, Parashivamurthy B. M., Shaik Kalimulla Niazi.
Background: The current therapeutic treatment of epilepsy with modern antiepileptic drugs is associated with side effects, dose related chronic toxicity, teratogenic effects and approximately 30% of the patients have intractable seizures. Natural products from folk remedies have contributed significantly in the discovery of modern drugs with novel structures and better safety and efficacy profiles. In this regard, one such plant is Nigella sativa. Objectives of the study was to evaluate the anticonvulsant activity of volatile oil extract of Nigella sativa seeds by pentylenetetrazole induced seizure model of epilepsy in albino rats and to evaluate the influence of volatile oil extract of Nigella sativa seeds on the anticonvulsant activity of sodium valproate in albino rats. Methods: Male Albino rats (150-200 gms) were randomly selected, from central animal facility, Mysore Medical College and Research Institute, Mysore. The anticonvulsant activity was screened using pentylenetetrazole model. Albino rats were divided into 6 groups of 6 rats each. 6 groups were treated with gum acacia 0.5 ml (control group), sodium valproate 300mg/kg (standard group), groups 3, 4, 5 were administered the test drug, volatile oil extract of Nigella sativa seeds at doses of 200 mg/kg, 400 mg/kg and 600 mg/kg and group 6 was treated with the combination of test drug, volatile oil extract of N. sativa seeds 200 mg/kg and sodium valproate 150 mg/kg. All the drugs were dissolved in gum acacia and administered intraperitoneally 30 min prior to induction of seizures. Results: The volatile oil of N. sativa seeds showed anticonvulsant activity at the dose of 400 mg/kg and 600mg/kg body weight and the potentiation of anticonvulsant activity of sodium valproate. The anticonvulsant activity of volatile oil of N. sativa seeds was less when compared to sodium valproate. Conclusions: The N. sativa seeds showed anticonvulsant activity in pentylenetetrazole induced seizure model of epilepsy. This study showed that volatile oil of N. sativa seeds potentiated the effect of sodium valproate.


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Study of biochemical abnormalities in neonatal seizures with special reference to hyponatremia

2016-07-04T03-27-13Z
Source: International Journal of Contemporary Pediatrics
Kamatham Madhusudhan, Nadavapalli Srinivasa Suresh, Talakola Ramesh Babu, Jampana venkateswara Rao, Surisetti Bharath Kumar.
Background: Biochemical abnormalities are commonly observed in neonates who are admitted in NICU with seizures. In these babies, biochemical abnormalities can be either primary or secondary. Secondary biochemical abnormalities are commonly observed in the presence of other obvious causes of seizures like HIE, meningitis etc. Hyponatremia, hypoglycemia and hypocalcemia are common metabolic disturbances found in neonates with seizures. The present study is intended to evaluate the incidence of various biochemical abnormalities especially hyponatremia. Methods: It is an observational study done in a tertiary care centre, Gandhi hospital, Secunderabad, Telangana, India involving 120 babies admitted with seizures in NICU. Results: Biochemical abnormalities were found in 52 babies with the most common primary abnormality being hypoglycemia mostly encountered in preterm babies and the most common secondary abnormality being hyponatremia seen mostly in term babies. Prompt identification of the biochemical abnormalities in neonatal seizures enables specific intervention by the treating doctor resulting in better neurological outcome. Conclusions: Early detection and prompt management of hyponatremia would help in preventing occurrence of seizures and also help in avoiding over use of anticonvulsants in the management of seizures resulting in favourable neurological outcome with less long term morbidity.


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Control of poisoning through product labeling of hazardous chemicals

2016-07-04T03-22-45Z
Source: Journal of the Pakistan Medical Association
Nadeem Ullah Khan, Arshad Iqbal, Sadaf Sheikh.



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Ramadan and diabetes: Holistic trial design

2016-07-04T03-22-45Z
Source: Journal of the Pakistan Medical Association
Fatema Jawad, Sanjay Kalra.
Extensive work has been done to analyze the safety of various modern glucose-lowering drugs during Ramadan fasting. This editorial suggests the use of validated scales of religiosity/spirituality as an adjunct to pre-Ramadan counselling and risk stratification. The editors also propose a holistic trial design for future trials on glycaemic management during Ramadan. Such a design should include both spiritual and biomedical endpoints, while trying to assess correlation between religiosity/spirituality and biomedical outcomes after Ramadan fasting. Integration of validated instruments to screen and monitor spirituality will help achieve the holistic health in devout Muslims who wish to observe Ramadan.


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Phenotypic expansion of TBX4 mutations to include acinar dysplasia of the lungs

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Mutations in the T-box transcription factor TBX4 gene have been reported in patients with Ischiocoxopodopatellar syndrome (MIM# 147891) and childhood-onset pulmonary arterial hypertension. Whole exome sequencing of DNA from a 1 day old deceased newborn, with severe diffuse developmental lung disorder exhibiting features of acinar dysplasia, and her unaffected parents identified a de novo TBX4 missense mutation p.E86Q (c.256G>C) in the DNA-binding T-box domain. We propose phenotypic expansion of the TBX4-related clinical disease spectrum to include acinar dysplasia of the lungs. The reported mutation is the first identified genetic variant causative for acinar dysplasia. © 2016 Wiley Periodicals, Inc.



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In memoriam: Dr. Andrew E. Czeizel (April 03, 1935–August 10, 2015)



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Genomic imbalance in the centromeric 11p15 imprinting center in three families: Further evidence of a role for IC2 as a cause of Russell–Silver syndrome

Russell–Silver syndrome is a heterogeneous disorder characterized by intrauterine growth retardation, postnatal growth deficiency, characteristic facial appearance, and other variable features. Genetic and epigenetic alterations are identified in about 60% of individuals with Russell–Silver syndrome. Most frequently, Russell–Silver syndrome is caused by altered gene expression on chromosome 11p15 due to loss of methylation at the telomeric imprinting center. To date there have been a handful of isolated clinical reports implicating the centromeric imprinting center 2 in the etiology of Russell–Silver syndrome. Here we report three new families with genomic imbalances, involving imprinting center 2 resulting in gain of methylation at this center and a Russell–Silver syndrome phenotype, including two families with a maternally inherited microduplication and the first pediatric patient with a paternally derived microdeletion. The findings in our families provide additional evidence of a role for imprinting center 2 in the etiology of Russell–Silver syndrome and suggest that imprinting center 2 imprinting abnormalities may be a more common cause of Russell–Silver syndrome than previously recognized. Furthermore, our findings together with previous clinical reports of genomic imbalances involving imprinting center 2 serve to underscore the complexity of the epigenetic regulation of the 11p15 region making it challenging to predict phenotype on the basis of genotype alone. © 2016 Wiley Periodicals, Inc.



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Electrolyte transport pathways induced in the midgut epithelium of Drosophila melanogaster larvae by commensal gut microbiota and pathogens

Abstract

Microbiota colonizing exposed epithelial surfaces are vital for sustenance of metazoan life, but communication between microbiota, epithelial cells and the host immune system is only beginning to be understood. We address this issue in the posterior midgut epithelium of Drosophila larvae where nutrient transport and immune functions are exclusively transcellular. We showed that larvae emerging into a sterile post-embryonic environment have symmetrical apical and basal membranes. In contrast, larvae emerging into non-sterile media, the source of microbiota, have markedly asymmetric membranes, with apical membrane conductance more than five-fold higher than the basal membranes. As an example of pathogen action, we showed that the entomopathogenic fungal toxin Destruxin A (Dx) depleted intracellular ions. Reversibility of action of Dx was verified by bilayer reconstitution in forming transient non-specific channels that conduct ions but not water. Dx was also less effective from the apical side as compared to the basal side of the epithelium. We also showed that intercellular septa are not conductive in non-sterile cells, even though most cells are isopotential. Luminal microbiota therefore impart asymmetry to the epithelium, by activation of apical membrane conductance, enhancing inter-enterocyte communication, separated by insulating septa, via the gut lumen. These results also open the possibility of studying the basis of bidirectional molecular conversation specifically between enterocytes and microbiota that enables discrimination between commensals and pathogens, establishment of the former, and elimination of the latter.

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Rescuing cardiac automaticity in L-type Cav1.3 channelopathies and beyond

Abstract

Pacemaker activity of the sino-atrial generates the heart rate. Disease of the sinus node and impairment of atrioventricular conduction induce an excessively low ventricular rate (bradycardia), which cannot meet the needs of the organism. Bradycardia accounts for about half of the total workload of clinical cardiologists. The "sick sinus" syndrome (SSS) is characterized by sinus bradycardia and periods of intermittent atrial fibrillation. Several genetic or acquired risk factors or pathologies can lead to SSS. Implantation of an electronic pacemaker constitutes the only available therapy for SSS. The incidence of SSS is forecasted to double over the next 50 years, with aging of the general population thus urging the development of complementary or alternative therapeutic strategies. In recent years an increasing number of mutations affecting ion channels involved in sino-atrial automaticity have been reported to underlie inheritable SSS. L-type Cav1.3 channels play a major role in the generation and regulation of sino-atrial pacemaker activity and atrioventricular conduction. Mutation in the CACNA1D gene encoding Cav1.3 channels induces loss-of-function in channel activity and underlies the Sino-Atrial Node Dysfunction and Deafness syndrome (SANDD). Mice lacking Cav1.3 channels (Cav1.3−/−) fairly recapitulate SSS and constitute a precious model to test new therapeutic approaches to handle this disease. Work in our laboratory shows that targeting G protein gated K+ (IKACh) channels effectively rescues SSS of Cav1.3−/− mice. This new concept of "compensatory" ion channel targeting shines new light in the principles underlying the pacemaker mechanism and may open the way to new therapies of SSS.

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Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons

Abstract

Excitotoxicity is thought to be one early process for the onset of amyotrophic lateral sclerosis (ALS) because high levels of glutamate have been detected in the cerebrospinal fluid of such patients due to dysfunctional uptake of this transmitter that gradually damages brainstem and spinal motoneurons. To explore potential mechanisms to arrest the disease onset, we used an established in vitro model of rat brainstem slice preparation in which excitotoxicity is induced by the glutamate uptake blocker, DL-threo-β-benzyloxyaspartate (TBOA). Because certain brain neurons may be neuroprotected via activation of nicotinic acetylcholine receptors (nAChRs) by nicotine, we investigated if nicotine could arrest excitotoxic damage to highly ALS-vulnerable hypoglossal motoneurons (HMs). On 50% of patch-clamped HMs, TBOA induced intense network bursts that were inhibited by 1–10 μm nicotine, whereas nAChR antagonists facilitated burst emergence in non-burster cells. Furthermore, nicotine inhibited excitatory transmission and enhanced synaptic inhibition. Strong neuroprotection by nicotine prevented the HM loss observed after 4 h of TBOA exposure. This neuroprotective action was due to suppression of downstream effectors of neurotoxicity like increased intracellular levels of reactive oxygen species, impaired energy metabolism and upregulated genes involved in endoplasmic reticulum (ER) stress. In addition, HMs surviving TBOA toxicity often expressed UDP-glucose glycoprotein glucosyltransferase, a key element to repair misfolded proteins: this phenomenon was absent after nicotine application, indicative of ER stress prevention. Our results suggest nAChRs to be potential targets for inhibiting excitotoxic damage of motoneurons at an early stage of the neurodegenerative process.

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Highly active antiretroviral therapy and changing spectrum of liver diseases in HIV infected patients

2016-07-04T02-33-04Z
Source: International Journal of Research in Medical Sciences
Kavita S. Joshi, Rohit R. Shriwastav.
Background: HIV is now considered as chronic disease than a fatal disease. HIV infected individual is having normal life expectancy post highly active antiretroviral therapy (HAART) era. Liver disease is the major cause of morbidity and mortality in HIV infected patients. The objective was to study the prevalence, clinical profile of various liver diseases in HIV infected individuals on HAART and also to study aetiologies of liver involvement in HIV patients. Methods: It was a cross sectional observational study conducted from August 2014 to July 2015. 102 HIV positive individuals on HAART with liver involvement were included. Detailed history and clinical examination were noted. Baseline investigations (Hb, CBC, blood sugars, liver function tests, electrocardiogram, chest X-ray, urine routine and microscopy), special investigations (HBsAg, anti-HCV, CD4 count, ultrasonography, CT scan, ascitic fluid examination) were performed. The data was analyzed using descriptive statistics. Results are expressed as percentage. Results: Out of the total 102 patients, 78 (76.5%) patients were male and 24 (23.5%) patients were female. The maximum number of patients belonged to the age group 41-50 years (38.2%). Hepatitis B (30.8%) was most common liver disease in males and AKT induced hepatitis (41.7%) most common liver disease in females. The most presenting symptom of patients with liver involvement in HIV was weakness and fatigue 82 (80.39%). The most common clinical sign was icterus 39 (38.23%), sonography finding was coarse echotexture of liver (46.07%) suggestive of cirrhosis. Conclusions: Although hepatitis B and alcoholic liver disease are major causes of liver diseases in HIV patients in India, incidence of drug related hepato toxicities are increasing.


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