Prodromal neuroinflammatory, cholinergic and metabolite dysfunction detected by PET and MRS in the TgF344-AD transgenic rat model of AD - a multi-modal and multi-centre study

Mouse models of Alzheimer's disease (AD) are valuable but do not fully recapitulate human AD pathology, such as spontaneous Tau fibril accumulation and neuronal loss, necessitating the development of new AD models. The transgenic (TG) TgF344-AD rat has been reported to develop age-dependent AD features including neuronal loss and neurofibrillary tangles, despite only expressing APP and PSEN1 mutations, suggesting an improved modelling of AD hallmarks. Alterations in neuronal networks as well as learning performance and cognition tasks have been reported in this model, but none have combined a longitudinal, multimodal approach across multiple centres, which mimics the approaches commonly taken in clinical studies. We therefore aimed to further characterise the progression of AD-like pathology and cognition in the TgF344-AD rat from young-adults (6 months (m)) to mid- (12 m) and advanced-stage (18 m, 25 m) of the disease

Effects of Physical Conditioning Program on Selected Physiological Variables of College Age Women Gymnasts

Higher Educatio

Poly(propylene glycol) and urethane dimethacrylates improve conversion of dental composites and reveal complexity of cytocompatibility testing.

OBJECTIVES: To determine the effects of various monomers on conversion and cytocompatibility of dental composites and to improve these properties without detrimentally affecting mechanical properties, depth of cure and shrinkage. METHODS: Composites containing urethane dimethacrylate (UDMA) or bisphenol A glycidyl methacrylate (Bis-GMA) with poly(propylene glycol) dimethacrylate (PPGDMA) or triethylene glycol dimethacrylate (TEGDMA) were characterized using the following techniques: conversion (FTIR at 1 and 4mm depths), depth of cure (BS EN ISO 4049:2009 and FTIR), shrinkage (BS EN ISO 17304:2013 and FTIR), strength and modulus (biaxial flexural test) and water sorption. Cytocompatibility of composites and their liquid phase components was assessed using three assays (resazurin, WST-8 and MTS). RESULTS: UDMA significantly improved conversion, BFS and depth of cure compared to Bis-GMA, without increasing shrinkage. UDMA was cytotoxic at lower concentrations than Bis-GMA, but extracts of Bis-GMA-containing composites were less cytocompatible than of those containing UDMA. PPGDMA improved conversion and depth of cure compared to TEGDMA, without detrimentally affecting shrinkage. TEGDMA was shown by all assays to be highly toxic. Resazurin, but not WST-8 and MTS, suggested that PPGDMA exhibited improved cytocompatibility compared to TEGDMA. SIGNIFICANCE: The use of UDMA and PPGDMA results in composites with excellent conversion, depth of cure and mechanical properties, without increasing shrinkage. Composites containing UDMA appear to be slightly more cytocompatible than those containing Bis-GMA. These monomers may therefore improve the material properties of dental restorations, particularly bulk fill materials. The effect of diluent monomer on cytocompatibility requires further investigation

Adverse drug reactions of Intermittent chemotherapy compared to daily regimen in Sudanese patients with pulmonary Tuberculosis

Back ground: The World Health Organization (WHO) declared Tuberculosis a global health emergency in 1993 as it remains a major cause of mortality in developing countries. The World Health Organization's Directly Observed Treatment Short course (DOTs) strategy achieve 87% success rate in the areas where it is implemented, usually with five drugs, lasts for 6months. Till 1998 Sudan was classified as one of the slowly moving countries in implementation of the DOTS strategy and making no progress against tuberculosis.Objective: A prospective comparative, randomized clinical trial, hospital based study carried out at Kosti Teaching Hospital using directly observed treatment short course (DOTS), to assess the adverse drug reactions of intermittent chemotherapy compared to the currently adopted short coursetherapy.Methodology: Patients with smear positive new cases of tuberculosis were enrolled and randomized in to two groups, intermittent treatment group (A) and daily regimen group (B) .The raw data were introduced into SPSS program, the data comparison was carried out by Pearson Chi square and pair independent sample student T-test. The level of significance (P<0.05).Results: A total of 275 were studied, significant initial (pre-interventional) elevated means of aspartate aminotransferase (AST) was detected in the two groups and significantly in the intermittent regimen after two and four months, but the decrease was significant only after two months in the daily group.Conclusion: Liver injury following antituberculous treatment was minimal and the adverse drug reactions were tolerable concerning the majority of the patients completing the course of the treatment.Keywords: DOTS, INH, acetylators

Atrial fibrillation in Middle Eastern Arabs and South Asians: a scoping review

Most of the published literature on Atrial fibrillation (AF) originates from the northern hemisphere and mainly involves Caucasian patients, with limited studies in certain ethnicities and races. This scoping review was conducted to collect and summarize the pertinent evidence from the published scientific literature on AF in South Asians and Middle Eastern Arabs. MEDLINE, Embase and CENTRAL databases were included in our search. After screening 8995 records, 55 studies were selected; 42 from the Middle East and 13 from South Asia. Characteristics of the included studies were tabulated, and their data were summarized for study design, setting, enrolment period, sample size, demographics, prevalence or incidence of AF, comorbidities, risk factors, AF types and symptoms, management, outcomes, and risk determinants. Identified literature gaps included a paucity of community or population-based studies that are representative of these two ethnicities/races. In addition, studies that addressed ethnic/racial in-equality and access to treatment were lacking. Our study underscores the urgent need to study cardiovascular disorders, particularly AF, in South Asians and Middle Eastern Arabs as well as in other less represented ethnicities and races

Breast cancer: detection markers, prognosis, and prevention

Breast cancer is the common invasive cancer with high mortality worldwide. High incidence of breast cancer in South and central America, Southren, Northren, Westren Europe, Ocenia and North America. Lowest breast cancer incidence in Africa and Asia. Risk factors includes: female sex old age, lifestyle, oralcontraceptive, hormone replacement therapy, mutations in the breast cancer susceptibility genes BRCA1orBRCA2.alcohol intake, hereditary factors, and exposure to chemicals. Breast cancer occurs because of an interaction between external factor and genetically susceptible host. Frequent symptoms of breast cancer is typically a lump and lumps found in the lymph node in the armpits. Diagnosis by physical examination of the breast and mammography. Further tests include histopathological examination, breast cells grading by TNM systeme.g., Zero stage a precancerous or marker condition, stage 1- 3 within the breast and regional nodes, and stage four is metastatic stage. Management of breast cancer depends on the stage of the cancer and age of the patient. Usually treated with surgery, chemotherapy or radiation therapy or both. A multidisciplinary approach is preferable. Metastatic cancer has less favorable prognosis. Prognosis is usually the probability of progression-free survival(PFS) or disease free survival(DFS).Prevention include change in life style, maintaining healthy weight, less alcohol consumption, and intake of marine omega-3 and soy-based foods Prophylactic mastectomy(removal of both breasts) helps in people with BRCA1 and BRCA2 mutations. Early detection of breast cancer has better prognosis

Burden of visceral leishmaniasis in villages of eastern gedaref state, Sudan: an exhaustive cross-sectional survey.

Since December 2009, Médecins Sans Frontières has diagnosed and treated patients with visceral leishmaniasis (VL) in Tabarak Allah Hospital, eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was conducted to estimate the VL incidence in villages around Tabarak Allah

Thermal- and Oxidative Stress Causes Enhanced Release of NKG2D Ligand-Bearing Immunosuppressive Exosomes in Leukemia/Lymphoma T and B Cells

Immune evasion from NK surveillance related to inadequate NK-cell function has been suggested as an explanation of the high incidence of relapse and fatal outcome of many blood malignancies. In this report we have used Jurkat and Raji cell lines as a model for studies of the NKG2D receptor-ligand system in T-and B cell leukemia/lymphoma. Using real-time quantitative RT-PCR and immunoflow cytometry we show that Jurkat and Raji cells constitutively express mRNA and protein for the stress-inducible NKG2D ligands MICA/B and ULBP1 and 2, and up-regulate the expression in a cell-line specific and stress-specific manner. Furthermore, we revealed by electron microscopy, immunoflow cytometry and western blot that these ligands were expressed and secreted on exosomes, nanometer-sized microvesicles of endosomal origin. Acting as a decoy, the NKG2D ligand-bearing exosomes downregulate the in vitro NKG2D receptor-mediated cytotoxicity and thus impair NK-cell function. Interestingly, thermal and oxidative stress enhanced the exosome secretion generating more soluble NKG2D ligands that aggravated the impairment of the cytotoxic response. Taken together, our results might partly explain the clinically observed NK-cell dysfunction in patients suffering from leukemia/lymphoma. The adverse effect of thermal and oxidative stress, enhancing the release of immunosuppressive exosomes, should be considered when cytostatic and hyperthermal anti-cancer therapies are designed

Image-Based Biological Heart Age Estimation Reveals Differential Aging Patterns Across Cardiac Chambers.

BACKGROUND: Biological heart age estimation can provide insights into cardiac aging. However, existing studies do not consider differential aging across cardiac regions. PURPOSE: To estimate biological age of the left ventricle (LV), right ventricle (RV), myocardium, left atrium, and right atrium using magnetic resonance imaging radiomics phenotypes and to investigate determinants of aging by cardiac region. STUDY TYPE: Cross-sectional. POPULATION: A total of 18,117 healthy UK Biobank participants including 8338 men (mean age = 64.2 ± 7.5) and 9779 women (mean age = 63.0 ± 7.4). FIELD STRENGTH/SEQUENCE: A 1.5 T/balanced steady-state free precession. ASSESSMENT: An automated algorithm was used to segment the five cardiac regions, from which radiomic features were extracted. Bayesian ridge regression was used to estimate biological age of each cardiac region with radiomics features as predictors and chronological age as the output. The "age gap" was the difference between biological and chronological age. Linear regression was used to calculate associations of age gap from each cardiac region with socioeconomic, lifestyle, body composition, blood pressure and arterial stiffness, blood biomarkers, mental well-being, multiorgan health, and sex hormone exposures (n = 49). STATISTICAL TEST: Multiple testing correction with false discovery method (threshold = 5%). RESULTS: The largest model error was with RV and the smallest with LV age (mean absolute error in men: 5.26 vs. 4.96 years). There were 172 statistically significant age gap associations. Greater visceral adiposity was the strongest correlate of larger age gaps, for example, myocardial age gap in women (Beta = 0.85, P = 1.69 × 10-26 ). Poor mental health associated with large age gaps, for example, "disinterested" episodes and myocardial age gap in men (Beta = 0.25, P = 0.001), as did a history of dental problems (eg LV in men Beta = 0.19, P = 0.02). Higher bone mineral density was the strongest associate of smaller age gaps, for example, myocardial age gap in men (Beta = -1.52, P = 7.44 × 10-6 ). DATA CONCLUSION: This work demonstrates image-based heart age estimation as a novel method for understanding cardiac aging. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 1

Genetic Insights from Consanguineous Cardiomyopathy Families.

Inherited cardiomyopathies are a prevalent cause of heart failure and sudden cardiac death. Both hypertrophic (HCM) and dilated cardiomyopathy (DCM) are genetically heterogeneous and typically present with an autosomal dominant mode of transmission. Whole exome sequencing and autozygosity mapping was carried out in eight un-related probands from consanguineous Middle Eastern families presenting with HCM/DCM followed by bioinformatic and co-segregation analysis to predict the potential pathogenicity of candidate variants. We identified homozygous missense variants in TNNI3K, DSP, and RBCK1 linked with a dilated phenotype, in NRAP linked with a mixed phenotype of dilated/hypertrophic, and in KLHL24 linked with a mixed phenotype of dilated/hypertrophic and non-compaction features. Co-segregation analysis in family members confirmed autosomal recessive inheritance presenting in early childhood/early adulthood. Our findings add to the mutational spectrum of recessive cardiomyopathies, supporting inclusion of KLHL24, NRAP and RBCK1 as disease-causing genes. We also provide evidence for novel (recessive) modes of inheritance of a well-established gene TNNI3K and expand our knowledge of the clinical heterogeneity of cardiomyopathies. A greater understanding of the genetic causes of recessive cardiomyopathies has major implications for diagnosis and screening, particularly in underrepresented populations, such as those of the Middle East