193 research outputs found
Prevention of Fungal Growth on Rubber Earpads of Telecommunication Equipments
This paper recommends an addition of 100% zinc oxide to the rubber composition during its manufacture to effectively prevent fungal growth on the earpads without producing any adverse on its materials/performance or the user
Enterobius vermicularis in the male urinary tract: a case report
Enterobius vermicularis is an intestinal nematode of humans. Adults usually have low worm burdens and are asymptomatic. Ectopic infections in the pelvic area or urinary tract rarely occur in women. We report a case of the patient with mild voiding difficulties such as urgency, frequency, nocturia, dysuria, mild low back pain or perineal discomfort. The patient's prostatic secretions showed a large number of inflammatory cells and several eggs. The size and the shape of the eggs identified them as a group of E. vermicularis. On examination we found a soft palpable material which was 5 mm diameter in size and spherical shape. Palpation gave the impression of a tissue than a stone. An incision was performed and a 4 mm long living worm was found. The microscopic examination identified the worm as E- vermicularis. It is an extremely rare manifestation of enterobius vermicularis infection since an intestinal-breeding worm is rarely found in the male genital tract
1H-NMR-Based Metabolomic Profiling of CSF in Early Amyotrophic Lateral Sclerosis
Background: Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to analyze the CSF of patients with ALS by 1 H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS. Methodology: CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional 1 H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses. Principal Findings: Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites reveale
Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS.
Many mutations confer one or more toxic function(s) on copper/zinc superoxide dismutase 1 (SOD1) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we found that oxidized wild-type SOD1 and mutant SOD1 share a conformational epitope that is not present in normal wild-type SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord were markedly C4F6 immunoreactive, indicating that an aberrant wild-type SOD1 species was present. Recombinant, oxidized wild-type SOD1 and wild-type SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal transport in a manner similar to that of FALS-linked mutant SOD1. Our findings suggest that wild-type SOD1 can be pathogenic in SALS and identify an SOD1-dependent pathogenic mechanism common to FALS and SALS
Amyotrophic Lateral Sclerosis: An Emerging Era of Collaborative Gene Discovery
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms (SNPs) that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples (such as DNA), phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS
The use of preoperative radiotherapy in the management of patients with clinically resectable rectal cancer: a practice guideline
BACKGROUND: This systematic review with meta-analysis was designed to evaluate the literature and to develop recommendations regarding the use of preoperative radiotherapy in the management of patients with resectable rectal cancer. METHODS: The MEDLINE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings of the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were systematically searched for evidence. Relevant reports were reviewed by four members of the Gastrointestinal Cancer Disease Site Group and the references from these reports were searched for additional trials. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee. RESULTS: Two meta-analyses of preoperative radiotherapy versus surgery alone, nineteen trials that compared preoperative radiotherapy plus surgery to surgery alone, and five trials that compared preoperative radiotherapy to alternative treatments were obtained. Randomized trials demonstrate that preoperative radiotherapy followed by surgery is significantly more effective than surgery alone in preventing local recurrence in patients with resectable rectal cancer and it may also improve survival. A single trial, using surgery with total mesorectal excision, has shown similar benefits in local recurrence. CONCLUSION: For adult patients with clinically resectable rectal cancer we conclude that: • Preoperative radiotherapy is an acceptable alternative to the previous practice of postoperative radiotherapy for patients with stage II and III resectable rectal cancer; • Both preoperative and postoperative radiotherapy decrease local recurrence but neither improves survival as much as postoperative radiotherapy combined with chemotherapy. Therefore, if preoperative radiotherapy is used, chemotherapy should be added postoperatively to at least patients with stage III disease
Corticosteroids for severe sepsis: an evidence-based guide for physicians
Septic shock is characterized by uncontrolled systemic inflammation that contributes to the progression of organ failures and eventually death. There is now ample evidence that the inability of the host to mount an appropriate hypothalamic-pituitary and adrenal axis response plays a major in overwhelming systemic inflammation during infections. Proinflammatory mediators released in the inflamed sites oppose to the anti-inflammatory response, an effect that may be reversed by exogenous corticosteroids. With sepsis, via nongenomic and genomic effects, corticosteroids restore cardiovascular homeostasis, terminate systemic and tissue inflammation, restore organ function, and prevent death. These effects of corticosteroids have been consistently found in animal studies and in most recent frequentist and Bayesian meta-analyses. Corticosteroids should be initiated only in patients with sepsis who require 0.5 μg/kg per minute or more of norepinephrine and should be continued for 5 to 7 days except in patients with poor hemodynamic response after 2 days of corticosteroids and with a cortisol increment of more than 250 nmol/L after a standard adrenocorticotropin hormone (ACTH) test. Hydrocortisone should be given at a daily dose of 200 mg and preferably combined to enteral fludrocortisone at a dose of 50 μg. Blood glucose levels should be kept below 150 mg/dL
Modeling CICR in rat ventricular myocytes: voltage clamp studies
<p>Abstract</p> <p>Background</p> <p>The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect <it>Ca</it><sup>2+ </sup>loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR <it>Ca</it><sup>2+ </sup>release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic <it>Ca</it><sup>2+ </sup>concentration ([<it>Ca</it><sup>2+</sup>]<it><sub>myo</sub></it>).</p> <p>Methods</p> <p>The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed <it>Ca</it><sup>2+ </sup>channels (trigger-channel and release-channel). It releases <it>Ca</it><sup>2+ </sup>flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[<it>Ca</it><sup>2+</sup>]<it><sub>myo</sub></it>.</p> <p>Results</p> <p>Our model reproduces measured VC data published by several laboratories, and generates graded <it>Ca</it><sup>2+ </sup>release at high <it>Ca</it><sup>2+ </sup>gain in a homeostatically-controlled environment where [<it>Ca</it><sup>2+</sup>]<it><sub>myo </sub></it>is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR <it>Ca</it><sup>2+ </sup>release, its activation by trigger <it>Ca</it><sup>2+</sup>, and its refractory characteristics mediated by the luminal SR <it>Ca</it><sup>2+ </sup>sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence <it>Ca</it><sup>2+ </sup>homeostasis.</p> <p>Conclusions</p> <p>We examine the role of the above <it>Ca</it><sup>2+ </sup>regulating mechanisms in handling various types of induced disturbances in <it>Ca</it><sup>2+ </sup>levels by quantifying cellular <it>Ca</it><sup>2+ </sup>balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses.</p
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