Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

State of the art review: the data revolution in critical care

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/annualupdate2015. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

National and subnational mortality effects of metabolic risk factors and smoking in Iran: a comparative risk assessment

<p>Abstract</p> <p>Background</p> <p>Mortality from cardiovascular and other chronic diseases has increased in Iran. Our aim was to estimate the effects of smoking and high systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC), and high body mass index (BMI) on mortality and life expectancy, nationally and subnationally, using representative data and comparable methods.</p> <p>Methods</p> <p>We used data from the Non-Communicable Disease Surveillance Survey to estimate means and standard deviations for the metabolic risk factors, nationally and by region. Lung cancer mortality was used to measure cumulative exposure to smoking. We used data from the death registration system to estimate age-, sex-, and disease-specific numbers of deaths in 2005, adjusted for incompleteness using demographic methods. We used systematic reviews and meta-analyses of epidemiologic studies to obtain the effect of risk factors on disease-specific mortality. We estimated deaths and life expectancy loss attributable to risk factors using the comparative risk assessment framework.</p> <p>Results</p> <p>In 2005, high SBP was responsible for 41,000 (95% uncertainty interval: 38,000, 44,000) deaths in men and 39,000 (36,000, 42,000) deaths in women in Iran. High FPG, BMI, and TC were responsible for about one-third to one-half of deaths attributable to SBP in men and/or women. Smoking was responsible for 9,000 deaths among men and 2,000 among women. If SBP were reduced to optimal levels, life expectancy at birth would increase by 3.2 years (2.6, 3.9) and 4.1 years (3.2, 4.9) in men and women, respectively; the life expectancy gains ranged from 1.1 to 1.8 years for TC, BMI, and FPG. SBP was also responsible for the largest number of deaths in every region, with age-standardized attributable mortality ranging from 257 to 333 deaths per 100,000 adults in different regions.</p> <p>Discussion</p> <p>Management of blood pressure through diet, lifestyle, and pharmacological interventions should be a priority in Iran. Interventions for other metabolic risk factors and smoking can also improve population health.</p

Transitions at CpG Dinucleotides, Geographic Clustering of TP53 Mutations and Food Availability Patterns in Colorectal Cancer

Colorectal cancer is mainly attributed to diet, but the role exerted by foods remains unclear because involved factors are extremely complex. Geography substantially impacts on foods. Correlations between international variation in colorectal cancer-associated mutation patterns and food availabilities could highlight the influence of foods on colorectal mutagenesis. mutations from 12 countries/geographic areas. For food availabilities, we relied on data extracted from the Food Balance Sheets of the Food and Agriculture Organization of the United Nations. Dendrograms for mutation sites, mutation types and food patterns were constructed through Ward's hierarchical clustering algorithm and their stability was assessed evaluating silhouette values. Feature selection used entropy-based measures for similarity between clusterings, combined with principal component analysis by exhaustive and heuristic approaches. hotspots. Pearson's correlation scores, computed between the principal components of the datamatrices for mutation types, food availability and mutation sites, demonstrated statistically significant correlations between transitions at CpGs and both mutation sites and availabilities of meat, milk, sweeteners and animal fats, the energy-dense foods at the basis of “Western” diets. This is best explainable by differential exposure to nitrosative DNA damage due to foods that promote metabolic stress and chronic inflammation

Determination of Reservoir(s) and Vector(s) of Cutaneous Leishmaniasis by Nested-PCR in Marvdasht District, Fars Province, Southern Iran

Abstract: Introduction: Cutaneous leishmaniasis (CL) is an increasing public health problem in several parts of Iran. In southern parts, the incidence of CL has been doubled over the last decade. This epidemiological study was done for determination of reservoir(s) and vector(s) of cutaneous leishmaniasis in rural regions of Marvdasht, Fars province, southern Iran during 2003 and 2004. Methods: A total of 126 rodents were collected from three villages using live traps and their Giemsa-stained smears were studied for leishmania infection. After DNA extraction from positive smears, Nested-PCR was used for the identification of parasite species. In another procedure, 200 sand flies were collected by aspirator and after species identification DNA extraction and PCR was done. Results: The collected samples included Meriones libycus (75.4%), Cricetulus migratorius (14.3%) and Microtus arualis (10.3%). Eight out of 95 Meriones libycus (8.4%) were found to be infected with Leishmania major. None of the other species were positive. Among the collected female sandflies 75% were identified to be Phlebotomus papatasi and 2.7% of them were found with L.major infection. Conclusion: Only 2.7% of Phlebotomus papatasi were found naturally infected with Leishmania major. This is the first report of detection of L.major by Nested-PCR in P.papatasi as a proven principal vector of zoonotic cutaneous leishmaniasis in Fars province, south of Iran. Keywords: Reservoir, Vector, Cutaneous leishmaniasis, Nested-PCR, Fars, Ira

Stem Cell Therapy in Liver Cirrhosis

Cirrhosis results from different mechanisms of liver injury that lead to necroinflammation and fibrogenesis; Patients with liver cirrhosis often require liver transplantation but it is affected by many problems, including relative operative damage, high costs, lack of donors, and risk of rejection. Currently studies are shown the Stem cell therapy has the potential to provide a valuable adjunct to the management of disease, Stem cell should be the natural candidates to provide a renewable source of cells for transplantation. The main mechanism of stem cell therapy is that stem cell capacity to differentiate into any of the hundreds of distinct cell types that comprise the human body. In addition to their potential in therapeutics can be used to study the earliest stages of human development and disease modeling using human cells. In this article, we review the potential for stem cell therapies to treat liver cirrhosis, MSCs cells are reprogrammed as useful sources of cells that can be change to liver cell for treatment of cirrhosis but pathological implication and autologous bone marrow stem cell therapy for cirrhosis are still to be elucidated and clinical trials that required before this cell transplantation must be performed in Large-scale controlled to becomes a regular therap