Cell shape regulates subcellular organelle location to control early Ca2+ signal dynamics in vascular smooth muscle cells.

The shape of the cell is connected to its function; however, we do not fully understand underlying mechanisms by which global shape regulates a cell's functional capabilities. Using theory, experiments and simulation, we investigated how physiologically relevant cell shape changes affect subcellular organization, and consequently intracellular signaling, to control information flow needed for phenotypic function. Vascular smooth muscle cells going from a proliferative and motile circular shape to a contractile fusiform shape show changes in the location of the sarcoplasmic reticulum, inter-organelle distances, and differential distribution of receptors in the plasma membrane. These factors together lead to the modulation of signals transduced by the M3 muscarinic receptor/Gq/PLCß pathway at the plasma membrane, amplifying Ca2+ dynamics in the cytoplasm, and the nucleus resulting in phenotypic changes, as determined by increased activity of myosin light chain kinase in the cytoplasm and enhanced nuclear localization of the transcription factor NFAT. Taken together, our observations show a systems level phenomenon whereby global cell shape affects subcellular organization to modulate signaling that enables phenotypic changes.

Enhanced durability, bio-activity and corrosion resistance of stainless steel through severe surface deformation.

Owing to its good biocompatibility and low cost, stainless steel is one of the most widely utilized biomaterial. However, longtime assessment of stainless steel has shown problems related to material degradation, especially localized corrosion and bio-film formation. In addition, the leaching of toxic nickel and chromium ions from stainless steel leads to additional health complications. Here, we utilized submerged friction stir processing, a severe surface deformation technique for significantly enhancing its durability, bio-activity as well as antibacterial resistance. The processing was done with a wide variation in strain rates to produce tunable surface microstructure. High strain-rate processing resulted in nearly single-phase fine-grained microstructure, while slow strain-rate processing developed a dual-phase fine-grained microstructure. The bio-corrosion rate of processed steel was reduced by more than 60 % along with significant enhancement in the pitting resistance. The processed steel showed nearly no bacterial adhesion/biofilm formation, evaluated using S. aureus and E. coli bacterial strains. Further, the processed stainless steel surface demonstrated minimum leaching of the toxic elements, significantly enhancing its appeal for bio-implant applications. The observed behavior was explained based on the formation of a stable passive layer, rich in Cr2O3, as determined using x-ray photoelectron microscopy (XPS) and increased hydrophilicity.

Friction Stir Processing of Stainless Steel for Ascertaining Its Superlative Performance in Bioimplant Applications.

Substrate-cell interactions for a bioimplant are driven by substrate's surface characteristics. In addition, the performance of an implant and resistance to degradation are primarily governed by its surface properties. A bioimplant typically degrades by wear and corrosion in the physiological environment, resulting in metallosis. Surface engineering strategies for limiting degradation of implants and enhancing their performance may reduce or eliminate the need for implant removal surgeries and the associated cost. In the current study, we tailored the surface properties of stainless steel using submerged friction stir processing (FSP), a severe plastic deformation technique. FSP resulted in significant microstructural refinement from 22 µm grain size for the as-received alloy to 0.8 µm grain size for the processed sample with increase in hardness by nearly 1.5 times. The wear and corrosion behavior of the processed alloy was evaluated in simulated body fluid. The processed sample demonstrated remarkable improvement in both wear and corrosion resistance, which is explained by surface strengthening and formation of a highly stable passive layer. The methylthiazol tetrazolium assay demonstrated that the processed sample is better in supporting cell attachment, proliferation with minimal toxicity, and hemolysis. The athrombogenic characteristic of the as-received and processed samples was evaluated by fibrinogen adsorption and platelet adhesion via the enzyme-linked immunosorbent assay and lactate dehydrogenase assay, respectively. The processed sample showed less platelet and fibrinogen adhesion compared with the as-received alloy, signifying its high thromboresistance. The current study suggests friction stir processing to be a versatile toolbox for enhancing the performance and reliability of currently used bioimplant materials.

Risk factors for diabetic retinopathy in self-reported rural population with diabetes.

BACKGROUND: Diabetes and its related microvascular complications like diabetic retinopathy (DR) are showing increased prevalence in India. However, the magnitude of DR in rural population with diabetes needs exploration. AIM: To estimate the prevalence and risk factors for the presence and severity of diabetic retinopathy in the self-reported rural population with diabetes. SETTINGS AND DESIGN: In a cross-sectional study, a total of 26,519 participants (age >or= 30 years) attended 198 diabetic retinopathy screening camps conducted in three southern districts of Tamilnadu, India, between February 2004 and April 2006. MATERIALS AND METHODS: All the participants underwent a dilated eye examination to detect DR by indirect ophthalmoscopy. Systemic and ocular risk factor estimation was done in a comprehensive examination. STATISTICAL ANALYSIS: Univariate and stepwise regression analyses were done to identify the independent risk factors associated with the presence and severity of retinopathy. RESULTS: The prevalence of diabetic retinopathy was 17.6% among the self-reported rural population with diabetes. The prevalence of referable (sight threatening) retinopathy was 5.3%. Risk factors associated with the development of any DR were male gender (OR= 1.37), longer duration of diabetes (per year, OR= 1.07), lean body mass index (OR= 1.30), higher systolic blood pressure (per 10 mm Hg, OR= 1.18), and insulin treatment (OR= 1.34; P P CONCLUSION: The study identified risk factors associated with DR in the rural population with diabetes. The results suggested that there was a need for formulating effective preventive strategies to minimize avoidable blindness due to diabetes, in rural areas.

Anti-bacterial activity of Euphorbia fusiformis--a rare medicinal herb.

Euphorbia fusiformis Buch.-Ham. ex. D.Don (Euphorbiaceae) is a rare medicinal herb. Aqueous and organic solvent extracts of the leaves and rootstocks were investigated for anti-bacterial properties by using disc diffusion and well-in agar methods, against pathogenic strains of Gram positive (Bacillus subtilis and Staphylococcus aureus) and Gram negative bacteria (Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella typhii A and Salmonella typhii B). The different extracts differed significantly in their anti-bacterial properties with the methanolic extract being very effective followed by acetone and chloroform extracts. Aqueous and ethanolic extract showed very least activity. The result highlights that rootstock extracts had good anti-bacterial properties than leaf extracts. The results of this study support the use of this plant in traditional medicine to treat fever, wound infections and intestinal disorders.

Sexual asphyxia: a lesser epidemic.

Asphyxiophilia is a paraphilia of the sacrificial/expiatory type in which sexual arousal and the attainment of gratification depend on hypoxia induced through either strangulation, smothering, chest compression and/or the inhalation of volatile substances. A peculiar, auto-erotic variant of this perversion is described, one in which the participant accidently died. Numerous female prostitutes have been canvassed in order to ascertain the prevalence in Durban, Republic of South Africa. The figures are an order of magnitude higher than was hitherto imagined. Insurance companies have been loathe to compensate the beneficiaries of such victims fully. How they and the courts view pivotal concepts such as 'mental infirmity', 'accident', 'natural consequences', and the legitimacy of psychiatry presenting itself as a unified body of knowledge sets precedents, and sets in motion processes whereby these decisions permeate into the general population and become--in time--accepted as norms. Thus, the medicolegal ramifications of sexual asphyxia affect not only the police and the courts, but also our society in general.