Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN--DREAMS III): Study design and research methodology

<p>Abstract</p> <p>Background</p> <p>To describe the methodology of the Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study III, an ongoing epidemiological study to estimate the prevalence of Diabetes and Diabetic Retinopathy in rural population of Kanchipuram and Thiravallur districts of Tamil Nadu, India and to elucidate the clinical, anthropometric, biochemical and genetic risk factors associated with diabetic retinopathy in this rural population.</p> <p>Methods</p> <p>Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study III will be a mobile van based epidemiological study; 11,760 participants aged ≥ 40 years will be recruited from the study areas. Eligible subjects will undergo blood sugar estimation to diagnose Diabetes. Oral Glucose Tolerance Test will be done to conform diabetes. All subjects with diabetes will undergo complete information of knowledge, aptitude and practice of diabetes and diabetic retinopathy, Diet questionnaire, demographic data, socioeconomic status, physical activity, anthropometric measurements, and risk of sleep apnoea. A detailed medical and ocular history, a comprehensive eye examination including refraction, slit lamp biomicroscopy examination, indirect ophthalmoscopy, slit lamp biomicroscopy, digital stereo fundus photography and ultrasound of eye will be done in the mobile van. Blood will be collected for biochemical investigations including blood hemoglobin, glycosylated hemoglobin, lipid profile, urea and creatinine, genetic study. Urine will be collected for microalbuminuria. All fundus photographs will be graded at base hospital. Participants who need treatment will be sent to the base hospital. A computerized database is created for the records.</p> <p>Conclusion</p> <p>The study is expected to provide an estimate of the prevalence of Diabetes and Diabetic Retinopathy and also a better understanding of the genetic, anthropometric and socio-economic risk factors associated with Diabetic Retinopathy in a Rural South Indian population.</p

Aging enhances serum cytokine response but not task-induced grip strength declines in a rat model of work-related musculoskeletal disorders

<p>Abstract</p> <p>Background</p> <p>We previously reported early tissue injury, increased serum and tissue inflammatory cytokines and decreased grip in young rats performing a moderate demand repetitive task. The tissue cytokine response was transient, the serum response and decreased grip were still evident by 8 weeks. Thus, here, we examined their levels at 12 weeks in young rats. Since aging is known to enhance serum cytokine levels, we also examined aged rats.</p> <p>Methods</p> <p>Aged and young rats, 14 mo and 2.5 mo of age at onset, respectfully, were trained 15 min/day for 4 weeks, and then performed a high repetition, low force (HRLF) reaching and grasping task for 2 hours/day, for 12 weeks. Serum was assayed for 6 cytokines: IL-1alpha, IL-6, IFN-gamma, TNF-alpha, MIP2, IL-10. Grip strength was assayed, since we have previously shown an inverse correlation between grip strength and serum inflammatory cytokines. Results were compared to naïve (grip), and normal, food-restricted and trained-only controls.</p> <p>Results</p> <p>Serum cytokines were higher overall in aged than young rats, with increases in IL-1alpha, IFN-gamma and IL-6 in aged Trained and 12-week HRLF rats, compared to young Trained and HRLF rats (p < 0.05 and p < 0.001, respectively, each). IL-6 was also increased in aged 12-week HRLF versus aged normal controls (p < 0.05). Serum IFN-gamma and MIP2 levels were also increased in young 6-week HRLF rats, but no cytokines were above baseline levels in young 12-week HRLF rats. Grip strength declined in both young and aged 12-week HRLF rats, compared to naïve and normal controls (p < 0.05 each), but these declines correlated only with IL-6 levels in aged rats (r = -0.39).</p> <p>Conclusion</p> <p>Aging enhanced a serum cytokine response in general, a response that was even greater with repetitive task performance. Grip strength was adversely affected by task performance in both age groups, but was apparently influenced by factors other than serum cytokine levels in young rats.</p

Assembly and Development of the Pseudomonas aeruginosa Biofilm Matrix

Virtually all cells living in multicellular structures such as tissues and organs are encased in an extracellular matrix. One of the most important features of a biofilm is the extracellular polymeric substance that functions as a matrix, holding bacterial cells together. Yet very little is known about how the matrix forms or how matrix components encase bacteria during biofilm development. Pseudomonas aeruginosa forms environmentally and clinically relevant biofilms and is a paradigm organism for the study of biofilms. The extracellular polymeric substance of P. aeruginosa biofilms is an ill-defined mix of polysaccharides, nucleic acids, and proteins. Here, we directly visualize the product of the polysaccharide synthesis locus (Psl exopolysaccharide) at different stages of biofilm development. During attachment, Psl is anchored on the cell surface in a helical pattern. This promotes cell–cell interactions and assembly of a matrix, which holds bacteria in the biofilm and on the surface. Chemical dissociation of Psl from the bacterial surface disrupted the Psl matrix as well as the biofilm structure. During biofilm maturation, Psl accumulates on the periphery of 3-D-structured microcolonies, resulting in a Psl matrix-free cavity in the microcolony center. At the dispersion stage, swimming cells appear in this matrix cavity. Dead cells and extracellular DNA (eDNA) are also concentrated in the Psl matrix-free area. Deletion of genes that control cell death and autolysis affects the formation of the matrix cavity and microcolony dispersion. These data provide a mechanism for how P. aeruginosa builds a matrix and subsequently a cavity to free a portion of cells for seeding dispersal. Direct visualization reveals that Psl is a key scaffolding matrix component and opens up avenues for therapeutics of biofilm-related complications