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.

Knowledge of HIV/AIDS and Attitude Toward Voluntary Counselling and Testing Among Antenatal Clinic Attendees at a Tertiary Care Hospital in India.

BACKGROUND/PURPOSE: Maternal to child transmission (MTCT) is responsible for over 90 % of all childhood HIV infections. Lack of awareness regarding HIV and preventive practices against MTCT maybe one of the reasons behind high HIV transmission rates. In our study, we assessed the knowledge of HIV/AIDS in antenatal women, attending a tertiary care hospital in India as well as their attitude toward voluntary counseling and testing (VCT) for HIV. MATERIALS AND METHODS: This was a cross-sectional descriptive study carried out from May-July 2012 using a pretested interview-based questionnaire given to 386 antenatal women after obtaining consent. Data were abstracted for knowledge of HIV, MTCT, and attitude toward VCT. Results were expressed as percentages using SPSS v.16 software. RESULTS: Amongst the respondents, 92.5 % had heard of HIV and in 41 % of them, the source of information was through mass media. 81 % were aware of sexual intercourse as a mode of transmission of HIV while 55 % knew that sharing sharp objects and infected blood products can spread HIV. 37.6 % of respondents were aware of MTCT and 44 % heard of antiretroviral therapy as a method of prevention of MTCT. While 68 % were willing to get tested for HIV, 18.9 % knew about the steps involved and 44 % knew where to get VCT. CONCLUSION: There exists a lack of adequate knowledge regarding HIV and preventive practices against MTCT. Health education and awareness campaigns on MTCT prevention and VCT promotion should target women in their antenatal period in order to increase acceptability and accessibility of these services.

Does psychosocial stress influence menstrual abnormalities in medical students?

A cross-sectional study was conducted among 164 students in a medical school in Pondicherry, India, by administering a questionnaire consisting of anthropometric data, menstrual history and psychosocial stress. Psychosocial stress was assessed using Perceived Stress Scale (PSS10). We observed that out of the 164 students who answered the questionnaire, students who reported premenstrual symptoms, irregular cycles and dysmenorrhoea severe enough to take medication had significantly higher mean PSS scores (p = 0.000, 0.025, 0.035, respectively). High stress (fourth quartile PSS score) was significantly associated with occurrence of premenstrual symptoms and dysmenorrhoea severe enough to take medication. Stress in medical students is associated with severe dysmenorrhoea, irregular cycles and premenstrual syndrome. This implies that interventions to reduce the stress can improve the menstrual health of medical students, thereby reducing future health risks and improving the quality of life.

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.

Variable predictive model based classification algorithm for effective separation of protein structural classes.

Variable predictive model based class discrimination (VPMCD) algorithm is proposed as an effective protein secondary structure classification tool. The algorithm mathematically represents the characteristics amino acid interactions specific to each protein structure and exploits them further to distinguish different structures. The new concept and the VPMCD classifier are established using well-studied datasets containing four protein classes as benchmark. The protein samples selected from SCOP and PDB databases with varying homology (25-100%) and non-uniform distribution of class samples provide challenging classification problem. The performance of the new method is compared with advanced classification algorithms like component coupled, SVM and neural networks. VPMCD provides superior performance for high homology datasets. 100% classification is achieved for self-consistency test and an improvement of 5% prediction accuracy is obtained during Jackknife test. The sensitivity of the new algorithm is investigated by varying model structures/types and sequence homology. Simpler to implement VPMCD algorithm is observed to be a robust classification technique and shows potential for effective extensions to other clinical diagnosis and data mining applications in biological systems.

Variable interaction network based variable selection for multivariate calibration.

Multivariate calibration problems often involve the identification of a meaningful subset of variables, from a vast number of variables for better prediction of output variables. A new graph theoretic method based on partial correlations (variable interaction network-VIN) is proposed. Many well studied representative calibration datasets spanning different application domains are selected for investigating the performance. Partial least squares (PLS) regression models combined with variable selection techniques are employed for benchmarking the performance. Subsets of variables with different number of variables are retained for the final analysis after VIN selection and progressive prediction accuracies are used for comparison. VIN-PLS results show significant improvement in prediction efficiencies and variable subset optimization. Improvement of up to 45% over existing methods with significantly fewer variables is achieved using the new method. Advantages of VIN based variable selection are highlighted.

Diabetic Retinopathy Analysis.

Diabetic retinopathy is one of the common complications of diabetes. Unfortunately, in many cases the patient is not aware of any symptoms until it is too late for effective treatment. Through analysis of evoked potential response of the retina, the optical nerve, and the optical brain center, a way will be paved for early diagnosis of diabetic retinopathy and prognosis during the treatment process. In this paper, we present an artificial-neural-network-based method to classify diabetic retinopathy subjects according to changes in visual evoked potential spectral components and an anatomically realistic computer model of the human eye under normal and retinopathy conditions in a virtual environment using 3D Max Studio and Windows Movie Maker.

Factors associated with low bone mineral density in female patients with systemic lupus erythematosus.

OBJECTIVE: To study risk factors for low bone mineral density (BMD, g/cm) in patients with systemic lupus erythematosus (SLE). METHODS: Ninety-two consecutive patients with SLE followed by rheumatology faculty between 1997 and 1999 completed a questionnaire regarding lifestyle during the clinic visit, a chart review was performed, and data were collected for the time of the first dual energy x-ray absorptiometry (DXA) examination. Univariate and multivariate statistical analyses were used to assess relationships between various risk factors and BMD. RESULTS: Ninety-eight percent of patients had received prednisone, 51% were postmenopausal (9 of whom received hormone replacement therapy), 68% had received hydroxychloroquine, and 15% were osteoporotic. The following factors were found to be significantly related to lower BMD by univariate analysis: Caucasian race, older age at diagnosis, higher age at the time of the first DXA, longer disease duration, higher cumulative corticosteroid dose, higher SLE Damage Index score, and postmenopausal status. In the multivariate analysis only the following factors were significant: Caucasian race, increased number of pregnancies, postmenopausal status, higher SLE Damage Index, and higher cumulative corticosteroid dose. An unexpected finding was that taking hydroxychloroquine was the only factor associated with higher BMD of the hip and spine in the univariate analysis, and it remained predictive of higher BMD of the hip and spine in the multivariate analysis. CONCLUSION: Hydroxychloroquine appears to protect against low BMD in corticosteroid treated patients with SLE.

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.

Sleep apnea syndrome in chronic spinal cord injury: associated factors and treatment.

OBJECTIVE: To determine the prevalence of sleep apnea in a sample of persons with chronic spinal cord injury (SCI) of varying injury levels and degrees of impairment. DESIGN: Cross-sectional study. SETTING: Inpatient SCI rehabilitation unit. PARTICIPANTS: Twenty men with SCI (motor complete and incomplete; American Spinal Injury Association classes A-D) of at least 1 year's duration, randomly selected from patients with SCI undergoing elective hospitalization. MAIN OUTCOME MEASURES: Apnea index, determined by sleep study (including chest wall movement, airflow, oxygen saturation), and daytime sleepiness, determined by Epworth sleepiness score. RESULTS: Eight subjects (40%) had sleep apnea, manifested by elevated apnea index (mean +/- SD, 17.1 +/- 6.9) and excessive daytime sleepiness. Sleep apnea was commonly diagnosed in motor-incomplete injuries. A trend (p = .07) existed toward a greater prevalence of sleep apnea with tetraplegia. Age and body mass index were not associated with sleep apnea. CONCLUSION: The prevalence of sleep apnea in men with chronic SCI admitted for nonrespiratory elective hospitalization is high relative to the general population.

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.

Shear-induced increase in hydraulic conductivity in endothelial cells is mediated by a nitric oxide-dependent mechanism.

This study addresses the role of nitric oxide (NO) and its downstream mechanism in mediating the shear-induced increase in hydraulic conductivity (L(p)) of bovine aortic endothelial cell monolayers grown on porous polycarbonate filters. Direct exposure of endothelial monolayers to 20-dyne/cm(2) shear stress induced a 4. 70+/-0.20-fold increase in L(p) at the end of 3 hours. Shear stress (20 dyne/cm(2)) also elicited a multiphasic NO production pattern in which a rapid initial production was followed by a less rapid, sustained production. In the absence of shear stress, an exogenous NO donor, S-nitroso-N-acetylpenicillamine, increased endothelial L(p) 2.23+/-0.14-fold (100 micromol/L) and 4.8+/-0.66-fold (500 micromol/L) at the end of 3 hours. In separate experiments, bovine aortic endothelial cells exposed to NO synthase inhibitors, N(G)-monomethyl-L-arginine and N(G)-nitro-L-arginine methyl ester, exhibited significant attenuation of shear-induced increase in L(p) in a dose-dependent manner. Inhibition of guanylate cyclase (GC) with LY-83,583 (1 micromol/L) or protein kinase G (PKG) with KT5823 (1 micromol/L) failed to attenuate the shear-induced increase in L(p). Furthermore, direct addition of a stable cGMP analogue, 8-bromo-cGMP, had no effect in altering baseline L(p), indicating that the GC/cGMP/PKG pathway is not involved in shear stress-NO-L(p) response. Incubation with iodoacetate (IAA), a putative inhibitor of glycolysis, dose-dependently increased L(p). Addition of IAA at levels that did not affect baseline L(p) greatly potentiated the response of L(p) to 20-dyne/cm(2) shear stress. Finally, both shear stress-induced and IAA-induced increases in L(p) could be reversed with the addition of dibutyryl cAMP. However, additional metabolic inhibitors, 2 deoxyglucose (10 mmol/L) and oligomycin (1 micromol/L), or reactive oxygen species scavengers, deferoxamine (1 mmol/L) and ascorbate (10 mmol/L), failed to alter shear-induced increases in L(p). Our results show that neither the NO/cGMP/PKG pathway nor a metabolic pathway mediates the shear stress-L(p) response. An alternate mechanism downstream from NO that is sensitive to IAA must mediate this response.

Effect of shear stress on the hydraulic conductivity of cultured bovine retinal microvascular endothelial cell monolayers.

The shear stress of flowing blood on endothelial cells increases water transport (hydraulic conductivity, Lp) in several vascular beds in vivo and has been hypothesized to play a role in elevating vascular transport in ocular diseases such as diabetic retinopathy. The purpose of this study is to determine the response of Lp to varying levels of shear stress using an in vitro model of the blood-retinal barrier: bovine retinal endothelial cells (BRECs) grown on polycarbonate filters. The study also addresses the role of nitric oxide (NO) and other downstream effectors in mediating shear-induced changes in water transport. A step change in shear stress of 10 dyn/cm(2) did not produce a significant change in Lp over 3 hours, whereas a 20 dyn/cm(2) step change elevated Lp by 14.6-fold relative to stationary controls at the end of 3h of shear exposure. 20 dyn/cm( 2) of shear stress stimulated the endothelial monolayers to release nitric oxide in a biphasic manner and incubation of the BRECs with a nitric oxide synthase (NOS) inhibitor, L-NMMA, significantly attenuated the shear-induced Lp response. These experiments demonstrate that NO is a key signaling molecule in the pathway linking shear stress and Lp in BRECs. A widely studied pathway downstream of NO involves the activation of guanylate cyclase (GC), guanosine 3', 5' -- cyclic monophosphate (cGMP) and protein kinase G (PKG). It was observed that incubation of BRECs with the GC inhibitor, LY83583 (10 microM) or the PKG inhibitor, KT5823 (1 microM) did not significantly alter the shear-induced Lp response. Also the cGMP analogue, 8-br-cGMP (1mM), did not affect the baseline Lp over 4h. These results demonstrate that shear stress elevates hydraulic conductivity in BRECs through a signaling mechanism that involves NO but not the GC/cGMP/PKG pathway.

Regulation of increase in anastomotic blood flow following pulmonary arterial occlusion.

We have previously shown that there is an acute increase in anastomotic bronchial blood flow (Qbr) after pulmonary arterial obstruction in dogs. We examined the role of arachidonic acid metabolites in mediating this increase. The left lower lobe (LLL) was isolated and perfused (zone 2) with autologous blood in open-chested anesthetized dogs (n = 19). Qbr was measured from the amount of blood that overflowed from the closed vascular circuit of the suspended LLL and changes in its weight. In the control animals, there was a prompt and significant increase in Qbr following pulmonary arterial obstruction. Pretreatment with indomethacin (n = 6) or sodium salicylate (n = 4) almost completely blocked this rise in Qbr. Following pulmonary arterial occlusion, there was a rise in both thromboxane and a prostacyclin metabolite (6-keto-PGF1 alpha) in the blood of the pulmonary circulation of the LLL, although the 6-keto-PGF1 alpha rose relatively more. Pretreatment with indomethacin caused a fall in both thromboxane and prostacyclin levels (n = 3), which no longer rose after pulmonary arterial occlusion. These findings suggested that the balance of the vasodilator (prostacyclin) and vasoconstrictor (thromboxane) prostaglandins may play an important role in mediating the rise in Qbr that follows pulmonary arterial obstruction.