Is the rural population of Puducherry district healthy in terms of the burden of non-communicable diseases? Findings from a cross-sectional analytical survey.

INTRODUCTION: Epidemiological transition remains a key contributor to the rising prevalence of non-communicable diseases (NCDs) across developing nations. Population-specific NCD risk factors estimates derived using World Health Organization (WHO) 'STEP-wise approach' are crucial for devising evidence-based public health interventions to combat NCDs. OBJECTIVE: To estimate the prevalence of behavioral and biological risk factors for NCDs among the rural adult population of Puducherry district in India. METHODOLOGY: STEPS survey was conducted by following all three steps (behavioral, physical measurements and biochemical risk factors) of NCD risk factor assessment. A total of 790 participants were selected from 50 villages through multistage cluster sampling method. STEPS instrument was used to assess behavioral risk factors, physical measurements and biochemical (fasting blood glucose and total cholesterol) risk factors. RESULTS: Tobacco use and alcohol consumption were present among 11.3% (95% Confidence Interval (CI): 9-13.6%) and 19.2% (95% CI: 16.5-22.4%) of the population, respectively. Low physical activity, inadequate intake of fruits and vegetables, overweight and obesity were observed among 29.3% (95% CI: 26.2-32.7%), 89.8% (95% CI: 87.6-92%), 15.6% (95% CI: 13.1-18.3%) and 38.9% (95% CI: 35.4-42.2%), respectively. About 28.2% (95% CI: 25.2-31.6%) had hypertension and 24.4% (95% CI: 20-29%) had diabetes mellitus. Abdominal obesity was twice highly prevalent among women. Tobacco and alcohol use were more common among men, whereas low physical activity, obesity and hypercholesterolemia were higher among women. CONCLUSION: Public health interventions to promote healthy lifestyle need to be initiated especially to increase physical activity, intake for fruits and vegetables, and quitting of tobacco and alcohol consumption in the rural population of Puducherry.

Global sensitivity analysis and model-based reactive scheduling of targeted cancer immunotherapy.

Intra-patient variability is a key challenge in cancer treatment. This makes it necessary to find the factors affecting tumor growth and accordingly schedule therapies over the treatment horizon for the patient. In this work, model-based studies are performed to investigate these issues for optimal immunotherapeutic intervention. Dendritic cell therapy is a targeted immunotherapy where the dendritic cells and its activating agents such as interleukin are engineered, stimulated to recognize and specifically eradicate tumors. A mathematical model that integrates tumor dynamics and dendritic cell therapy is used to perform the analysis. Global sensitivity analysis of the model is done using high dimensional model reduction (HDMR) technique and the key parameters altering the tumor growth are identified. The variations in these key parameters are deemed to result in intra-patient variability during the treatment phase. Then, reactive scheduling is used to schedule dendritic cell interventions with and without interleukin interventions under the varying conditions of the patient. Moreover, the key parameters obtained from HDMR are verified using the reactive scheduling and nominal scheduling approaches. Besides saving costs, the in silico analysis done in this paper may be useful to the oncology community in designing experiments to clinically measure the influential parameters. It can also be used as a decision making tool to determine the required intervention dosage during the treatment.

Twenty-year follow-up: an unusual case of nephropathy of antiphospholipid syndrome.

Nephropathy of antiphospholipid antibody syndrome (NAPS) is an increasingly well-recognized aspect of antiphospholipid syndrome. The most characteristic histopathology is that of thrombotic microangiopathy, and thrombosis occurring in the renal vasculature is thought to be the initiating event. Other less common pathologies have been reported, and the mechanisms of these are unclear. Therapy has been largely empiric. We report a case of NAPS in a patient with atypical pathology, who has declined therapy with immunosuppressive agents and anticoagulants and who has maintained normal renal function in 20 years of follow-up.

Effect of VEGF on retinal microvascular endothelial hydraulic conductivity: the role of NO.

PURPOSE: Vascular endothelial growth factor (VEGF) increases microvascular permeability in vivo and has been hypothesized to play a role in plasma leakage in diabetic retinopathy. Few controlled studies have been conducted to determine the mechanism underlying the effect of VEGF on transport properties (e.g., hydraulic conductivity [Lp]). This study was conducted to determine the effect of VEGF on bovine retinal microvascular endothelial LP and the role of nitric oxide (NO) and the guanylate cyclase/guanosine 3', 5'-cyclic monophosphate/protein kinase G (GC/cGMP/PKG) pathway downstream of NO in mediating the VEGF response. METHODS: Bovine retinal microvascular endothelial cells (BRECs) were grown on porous polycarbonate filters, and water flux across BREC monolayers in response to a pressure differential was measured to determine endothelial LP RESULTS: VEGF (100 ng/ml) increased endothelial LP: within 30 minutes of addition and by 13.8-fold at the end of 3 hours of exposure. VEGF stimulated endothelial monolayers to release NO and incubation of the BRECs with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 100 microM) significantly attenuated the VEGF-induced LP increase. It was observed that incubation of the monolayers with the GC inhibitor LY-83583 (10 microM) did not alter the VEGF-mediated LP: response. Addition of the cGMP analogue 8-br-cGMP (1 mM) did not change the baseline LP over 4 hours. Also, the PKG inhibitor KT5823 (1 microM) did not inhibit the response of BREC LP to VEGF. CONCLUSIONS: These experiments indicate that VEGF elevates hydraulic conductivity in BRECs through a signaling mechanism that involves NO but not the GC/cGMP/PKG pathway.

Effect of vascular endothelial growth factor on cultured endothelial cell monolayer transport properties.

Vascular endothelial growth factor (VEGF) is a potent enhancer of microvascular permeability in vivo. To date, its effects on hydraulic conductivity (L(p)) and diffusive albumin permeability (P(e)) of endothelial monolayers have not been thoroughly assessed in vitro. We hypothesized that VEGF affects endothelial transport properties differently depending on vessel location and endothelial phenotype. Using three well-established endothelial cell culture models-human umbilical vein endothelial cells (HUVECs), bovine aortic endothelial cells (BAECs), and bovine retinal microvascular cells (BRECs)-grown on porous, polycarbonate filters we were able to produce baseline transport properties characteristic of restrictive barriers. Our results show 3.1-fold and 5.7-fold increases in endothelial L(p) for BAEC and BREC monolayers, respectively, at the end of 3 h of VEGF (100 ng/ml) exposure. HUVECs, however, showed no significant alteration in L(p) after 3 h (100 ng/ml) or 24 h (25 ng/ml) of incubation with VEGF even though they were responsive to the inflammatory mediators, thrombin (1 U/ml; 27-fold increase in L(p) in 25 min) and bradykinin (10 microM; 4-fold increase in L(p) in 20 min). Protein kinase C (PKC) and nitric oxide (NO) are downstream effectors of VEGF signaling. BAEC L(p) was responsive to activation of NO (SNAP) and PKC (PMA), whereas these agents had no effect in altering HUVEC L(p). Moreover, BAECs exposed to the PKC inhibitor, staurosporine (50 ng/ml), exhibited significant attenuation of VEGF-induced increase in L(p), but inhibition of nitric oxide synthase (NOS) with L-NMMA (100 microM) had no effect in altering the VEGF-induced increase in L(p). These data provide strong evidence that in BAECs, the VEGF-induced increase in L(p) is mediated by a PKC-dependent mechanism. Regarding diffusive albumin P(e), at the end of 3 h, BAECs and BRECs showed 6.0-fold and 9. 9-fold increases in P(e) in response to VEGF (100 ng/ml), whereas VEGF had no significant effect after 3 h (100 ng/ml) or 24 h (25 ng/ml) in changing HUVEC P(e). In summary, these data indicate that VEGF affects endothelial transport properties differently depending on the vessel type and that differences in cell signaling pathways underlie the differences in VEGF responsiveness.