Alcohol-induced autonomic dysfunction: a systematic review

Purpose Autonomic dysfunction is a known consequence of chronic and excessive alcohol consumption. The aim of this systematic review was to characterise this phenomenon, describe the frequency at which it occurs and to explore the best management strategies. Methods A systematic, computer-based search was conducted using the PubMed database. All studies identified by the search were evaluated independently by at least three authors. For inclusion, studies had to report human subjects consuming ethanol in excess. Case reports and non-original studies were excluded from this review. Results A total of 55 studies were included in this review. According to cardiovascular reflex tests, 16–73% of chronic alcohol abusers suffer from autonomic dysfunction. The most commonly occurring symptom is erectile dysfunction, whilst other features such as postural dizziness are rare. The most important risk factor for this condition is total lifetime dose of ethanol, although there is mixed evidence supporting the role of other risk factors. The only management strategy currently explored in the literature is abstinence, which appears to lead to significant improvement in autonomic investigations. Conclusion Current literature includes studies of highly heterogeneous populations, consuming differing volumes of alcohol over variable periods of time and utilising a number of different autonomic test batteries and criteria to diagnose autonomic dysfunction. Therefore, further research using homogeneous methods for measuring autonomic dysfunction in the field is needed. Despite this limitation, our review demonstrated that autonomic dysfunction is very common among alcohol abusers

B12 as a treatment for peripheral neuropathic pain : a systematic review

Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain are debilitating and improved treatment regimens are sought in order to improve the quality of life of patients. One proposed treatment for neuropathic pain is vitamin B12, which is thought to alleviate pain by a number of mechanisms including promoting myelination, increasing nerve regeneration and decreasing ectopic nerve firing. In this paper, the evidence for B12 as a drug treatment for neuropathic pain is reviewed. Twenty four published articles were eligible for inclusion in this systematic review in which a range of treatment regimens were evaluated including both B12 monotherapy and B12 in combination with other vitamins or conventional treatments, such as gabapentinoids. Overall, this systematic review demonstrates that there is currently some evidence for the therapeutic effect of B12 in the treatment of post-herpetic neuralgia (level II evidence) and the treatment of painful peripheral neuropathy (level III evidence)

Exogenously-sourced ethylene increases stomatal conductance, photosynthesis, and growth under optimal and deficient nitrogen fertilization in mustard

In order to ascertain the stomatal and photosynthetic responses of mustard to ethylene under varying N availability, photosynthetic characteristics of mustard grown with optimal (80 mg N kg−1 soil) or low (40 mg N kg−1 soil) N were studied after the application of an ethylene-releasing compound, ethephon (2-chloroethyl phosphonic acid) at 40 days after sowing (DAS). The availability of N influenced ethylene evolution and affected stomatal conductance and photosynthesis. The effect of ethylene was smaller under deficient N where plants contained higher glucose (Glc) sensitivity, despite high ethylene evolution even in the absence of ethephon, potentially because the plants were less sensitive to ethylene per se. Ethephon application at each level of N increased ethylene and decreased Glc sensitivity, which increased photosynthesis via its effect on the photosynthetic machinery and effects on stomatal conductance. Plants grown with sufficient-N and treated with 200 μl l−1 ethephon exhibited optimal ethylene, the greatest stomatal conductance and photosynthesis, and growth. These plants made maximum use of available N and exhibited the highest nitrogen-use efficiency (NUE)

SMAD4 - Molecular gladiator of the TGF-β signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene

<p>Abstract</p> <p>Background</p> <p>The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the <it>SMAD4 </it>gene mutations with <it>KRAS </it>mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of <it>SMAD4 </it>gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and <it>KRAS </it>mutant genotype.</p> <p>Methods</p> <p>We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of <it>SMAD4 </it>and exon 1 of <it>KRAS </it>by PCR-SSCP and/or PCR-Direct sequencing.</p> <p>Results</p> <p>The overall mutation rate of mutation cluster region (MCR) region of <it>SMAD4 </it>gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the <it>SMAD4 </it>gene mutants were found to have mutations in <it>KRAS </it>gene as well. The association between the <it>KRAS </it>mutant genotype with <it>SMAD4 </it>mutants was found to be significant (P =< 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the <it>SMAD4 </it>gene (P =< 0.05).</p> <p>Conclusion</p> <p>Our study suggests that <it>SMAD4 </it>gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the <it>KRAS </it>mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.</p

Techniques of EMG signal analysis: detection, processing, classification and applications

Electromyography (EMG) signals can be used for clinical/biomedical applications, Evolvable Hardware Chip (EHW) development, and modern human computer interaction. EMG signals acquired from muscles require advanced methods for detection, decomposition, processing, and classification. The purpose of this paper is to illustrate the various methodologies and algorithms for EMG signal analysis to provide efficient and effective ways of understanding the signal and its nature. We further point up some of the hardware implementations using EMG focusing on applications related to prosthetic hand control, grasp recognition, and human computer interaction. A comparison study is also given to show performance of various EMG signal analysis methods. This paper provides researchers a good understanding of EMG signal and its analysis procedures. This knowledge will help them develop more powerful, flexible, and efficient applications

Structural insights into the catalytic mechanism of Trypanosoma cruzi GPXI (glutathione peroxidase-like enzyme I).

Current drug therapies against Trypanosoma cruzi, the causative agent of Chagas disease, have limited effectiveness and are highly toxic. T. cruzi-specific metabolic pathways that utilize trypanothione for the reduction of peroxides are being explored as potential novel therapeutic targets. In the present study we solved the X-ray crystal structure of one of the T. cruzi enzymes involved in peroxide reduction, the glutathione peroxidase-like enzyme TcGPXI (T. cruzi glutathione peroxidase-like enzyme I). We also characterized the wild-type, C48G and C96G variants of TcGPXI by NMR spectroscopy and biochemical assays. Our results show that residues Cys48 and Cys96 are required for catalytic activity. In solution, the TcGPXI molecule readily forms a Cys48-Cys96 disulfide bridge and the polypeptide segment containing Cys96 lacks regular secondary structure. NMR spectra of the reduced TcGPXI are indicative of a protein that undergoes widespread conformational exchange on an intermediate time scale. Despite the absence of the disulfide bond, the active site mutant proteins acquired an oxidized-like conformation as judged from their NMR spectra. The protein that was used for crystallization was pre-oxidized by t-butyl hydroperoxide; however, the electron density maps clearly showed that the active site cysteine residues are in the reduced thiol form, indicative of X-ray-induced reduction. Our crystallographic and solution studies suggest a level of structural plasticity in TcGPXI consistent with the requirement of the atypical two-cysteine (2-Cys) peroxiredoxin-like mechanism implied by the behaviour of the Cys48 and Cys96 mutant proteins

B12 as a treatment for peripheral neuropathic pain: A systematic review

Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain are debilitating and improved treatment regimens are sought in order to improve the quality of life of patients. One proposed treatment for neuropathic pain is vitamin B12, which is thought to alleviate pain by a number of mechanisms including promoting myelination, increasing nerve regeneration and decreasing ectopic nerve firing. In this paper, the evidence for B12 as a drug treatment for neuropathic pain is reviewed. Twenty four published articles were eligible for inclusion in this systematic review in which a range of treatment regimens were evaluated including both B12 monotherapy and B12 in combination with other vitamins or conventional treatments, such as gabapentinoids. Overall, this systematic review demonstrates that there is currently some evidence for the therapeutic effect of B12 in the treatment of post-herpetic neuralgia (level II evidence) and the treatment of painful peripheral neuropathy (level III evidence). © 2020 by the authors. Licensee MDPI, Basel, Switzerland