761 research outputs found

    Reversal of Pathogen-Induced Barrier Defects in Intestinal Epithelial Cells by Contra-pathogenicity Agents.

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    “This is a post-peer-review, pre-copyedit version of a protocol published in Digestive Diseases and Sciences The final publication is available at https://doi.org/10.1007/s10620-020-06121-9"BACKGROUND: Environmental enteropathy (EE) is associated with stunting, impairment of responses to oral vaccines, and other adverse health consequences in young children throughout the developing world. EE is characterized by chronic low-grade intestinal inflammation and disrupted epithelial barrier integrity, partly resulting from dysregulation of tight junction proteins, observed in other enteropathies such as celiac disease. During EE, this dysregulation of tight junction expression amplifies translocation of pathogenic bacteria across the intestinal mucosa. AIMS: The aim was to determine whether enteropathogen-mediated epithelial barrier failure can be ameliorated using contra-pathogenicity therapies. METHODS: Intestinal epithelial barrier damage was assessed in Caco-2 cells incubated with three important enteropathogens identified in EE patients: Enteropathogenic Escherichia coli (EPEC), Citrobacter rodentium (C. rodentium), and Cryptosporidium parvum (C. parvum). Potential therapeutic molecules were tested to detect effects on transepithelial resistance (TER), bacterial translocation (BT), claudin-4 expression, and regulation of the inflammatory cytokine response. RESULTS: All three enteropathogens compared to uninfected cells, reduced TER (EPEC; p < 0.0001, C. rodentium; p < 0.0001, C. parvum; p < 0.0007), reduced claudin-4 expression, and permitted BT (EPEC; p < 0.0001, C. rodentium; p < 0.0001, C. parvum; p < 0.0003) through the monolayer. Zinc, colostrum, epidermal growth factor, trefoil factor 3, resistin-like molecule-β, hydrocortisone, and the myosin light chain kinase inhibitor ML7 (Hexahydro-1-[(5-iodo-1-naphthalenyl)sulfonyl]-1H-1,4-diazepine hydrochloride); ML7) improved TER (up to 70%) and decreased BT (as much as 96%). Only zinc demonstrated modest antimicrobial activity. CONCLUSION: The enteropathogens impaired intestinal-epithelial barrier integrity with dysregulation of claudin-4 and increased bacterial translocation. Enteropathogen-mediated damage was reduced using contra-pathogenicity agents which mitigated the effects of pathogens without direct antimicrobial activity

    Effectiveness of e-learning in continuing medical education for occupational physicians

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    Background Within a clinical context e-learning is comparable to traditional approaches of continuing medical education (CME). However, the occupational health context differs and until now the effect of postgraduate e-learning among occupational physicians (OPs) has not been evaluated

    Damage in single lap joints of woven fabric reinforced polymeric composites subjected to transverse impact loading

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    Single lap joints of woven glass fabric reinforced phenolic composites, having four different overlap widths, were impacted transversely using a hemispherical impactor with different velocities in the low velocity impact range. The resulting damage was observed at various length scales (from micro to macro) using transmission photography, ultrasonic c-scan and x-ray micro tomography (XMT), in support of each other. These experimental observations were used for classification of damage in terms of damage scale, location (i.e. ply, interfaces between plies or bond failure between the two adherends) and mechanisms, with changing overlap width and impact velocity. In addition, finite element analysis was used to simulate delamination and disbond failure. These simulations were used to further explain the observed dependence of damage on overlap width and impact velocity. The results from these experiments and simulations lead to the proposal of a concept of lower and upper characteristic overlap width. These bounds relate the dominant damage pattern (i.e. scale, location and mechanism) with overlap width of the joint for a given impact velocity range.National University of Sciences and Technology, NUST, Pakistan: The University of Manchester, EPS fellowshi

    Reintroduction of elective cardiac interventions in the era of COVID-19: the Barts experience.

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    BACKGROUND: The response to COVID-19 has required cancellation of all but the most urgent procedures; there is therefore a need for the reintroduction of a safe elective pathway. METHODS: This was a study of a pilot pathway performed at Barts Heart Centre for the admission of patients requiring elective coronary and structural procedures during the COVID-19 pandemic (April-June 2020). All patients on coronary and structural waiting lists were screened for procedural indications, urgency and adverse features for COVID-19 prognosis and discussed at dedicated multidisciplinary teams. Dedicated admission pathways involving preadmission isolation, additional consent, COVID-19 PCR testing and dedicated clean areas were used. RESULTS: 143 patients (101 coronary and 42 structural) underwent procedures (coronary angiography, percutaneous coronary intervention, transcatheter aortic valve intervention and MitralClip) during the study period. The average age was 68.2; 74% were male; and over 93% had one or more moderate COVID-19 risk factors. All patients were COVID-19 PCR negative on admission with (8.1%) COVID-19 antibody positive (swab negative). All procedures were performed successfully with low rates of procedural complications (9.8%). At 2-week follow-up, no patients had symptoms or confirmed COVID-19 infection with significant improvements in quality if life and symptoms. CONCLUSION: We demonstrated that patients undergoing coronary and structural procedures can be safely admitted during the COVID-19 pandemic, with no patients contracting COVID-19 during their admission. Reassuringly, patients reflective of typical practice, that is, those at moderate or higher risk, were treated successfully. This pilot provides important information applicable to other settings, specialties and areas to reintroduce services safely

    Early and accurate detection of melanoma skin cancer using hybrid level set approach

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    Digital dermoscopy is used to identify cancer in skin lesions, and sun exposure is one of the leading causes of melanoma. It is crucial to distinguish between healthy skin and malignant lesions when using computerised lesion detection and classification. Lesion segmentation influences categorization accuracy and precision. This study introduces a novel way of classifying lesions. Hair filters, gel, bubbles, and specular reflection are all options. An improved levelling method is employed in an innovative method for detecting and removing cancerous hairs. The lesion is distinguished from the surrounding skin by the adaptive sigmoidal function; this function considers the severity of localised lesions. An improved technique for identifying a lesion from surrounding tissue is proposed in the article, followed by a classifier and available features that resulted in 94.40% accuracy and 93% success. According to research, the best method for selecting features and classifications can produce more accurate predictions before and during treatment. When the recommended strategy is put to the test using the Melanoma Skin Cancer Dataset, the recommended technique outperforms the alternative

    Bounds for Lepton Flavor Violation and the Pseudoscalar Higgs in the General Two Higgs Doublet Model using g−2g-2 muon factor

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    Current experimental data from the g−2g-2 muon factor, seems to show the necessity of physics beyond the Standard Model (SM), since the difference between SM and experimental predictions is 2.6σ\sigma . In the framework of the General Two Higgs Doublet Model (2HDM), we calculate the muon anomalous magnetic moment to get lower and upper bounds for the Flavour Changing (FC) Yukawa couplings in the leptonic sector. We also obtain lower bounds for the mass of the pseudoscalar Higgs (mA0m_{A^0}) as a function of the parameters of the model.Comment: 12 pages, RevTex4, 5 figures. Improved presentation, updated experimental data, amplified analysis, new figures added. Subbmited to Phys. Rev.

    Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study

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    Background: Alemtuzumab efficacy versus subcutaneous interferon-β-1a (SC IFNB-1a) was demonstrated over 2 years in patients with relapsing-remitting multiple sclerosis, with continued efficacy over 7 additional years. Alemtuzumab is included as a recommended treatment for patients with highly active disease (HAD) by the American Academy of Neurology Practice Guidelines, and the label indication in Europe was recently restricted to the treatment of HAD patients. There is currently no consensus definition for HAD, and alemtuzumab efficacy across various HAD definitions has not been explored previously. Objectives: In this post hoc analysis, we assess the efficacy and safety of alemtuzumab in Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) trial patients who met criteria for at least one of four separate definitions of HAD (one primary and three alternatives). Over 2 years, alemtuzumab-treated HAD patients were compared with SC IFNB-1a-treated HAD patients, with additional 7-year follow-up in patients from the alemtuzumab arm. Methods: Patients in the CARE-MS studies received either alemtuzumab (baseline: 5&nbsp;days; 12&nbsp;months later: 3&nbsp;days) or SC IFNB-1a (3 times weekly). Alemtuzumab-treated patients who enrolled in the extensions could receive additional courses ≥ 12&nbsp;months apart. Four definitions of HAD were applied to assess alemtuzumab efficacy: the pre-specified primary definition (two or more relapses in the year prior to baseline and at least one gadolinium [Gd]-enhancing lesion at baseline) and three alternative definitions that focused on relapse, magnetic resonance imaging (MRI), or prior treatment response criteria. Efficacy outcomes were annualized relapse rate, change in Expanded Disability Status Scale score, 6-month confirmed disability worsening, 6-month confirmed disability improvement, MRI disease activity, and brain volume change. Adverse events were summarized for HAD patients meeting the primary definition. Results: In the pooled CARE-MS population, 208 alemtuzumab-treated patients met the primary HAD definition. Annualized relapse rate was 0.27 in years 0–2 and 0.16 in years 3–9. Over 9 years, 62% of patients were free of 6-month confirmed disability worsening, 50% had 6-month confirmed disability improvement, and median cumulative change in brain volume was − 2.15%. During year 9, 62% had no evidence of disease activity, and 69% were free of MRI disease activity. Similar efficacy outcomes were observed using an alternative relapse-driven HAD definition. For patients meeting alternative HAD definitions focused on either higher MRI lesion counts or disease activity while on prior therapy, reduced efficacy for some endpoints was seen. Safety was consistent with the overall CARE-MS population through year 9. Conclusions: Over 9&nbsp;years, alemtuzumab efficacy was maintained in CARE-MS HAD patients based on four HAD definitions. These results support intervention with alemtuzumab in patients with early indicators of HAD, including frequent relapse without high MRI activity. No safety signals were observed over 9&nbsp;years that were unique to the HAD populations. ClinicalTrials.gov Identifiers: NCT00530348; NCT00548405; NCT00930553; NCT02255656
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