Demographic and clinical characteristics of primary lung cancer patients in Kerala: Analysis of data from six teaching centers.

Background: Lung cancer continues to be the leading cause of cancer-related deaths in men and women. A breakdown by level of economic development shows no differences in cancer deaths in men but a higher rate of lung cancer deaths in women in industrialized countries as compared with developing nations. The risk factors for lung cancer most commonly include lifestyle, environmental, and occupational exposures. The role these factors play varies depending on geographic location, sex and race characteristics, genetic predisposition, as well as their synergistic interactions. Materials and Methods: It was a hospital-based registry, wherein hospitals were selected from three zones-north, central, and south zones of Kerala. The study was registered with clinical trial registry of India with Registration No. CTRI/2021/02/031299. Registry of lung cancer patients was prepared at all sites and institutional ethical clearance was received from all sites. All patients with primary lung cancer, histologically proven of all age groups were included in the study. Results: A total of 761 patients were registered from six teaching hospitals in Kerala who were diagnosed with primary lung cancer during the period 2017-2019. The mean age of the study population was 65.1 ± 10.2 years. Of all, 81.1% of them were males and 18.9% were females. Histologically, 56.4% had adenocarcinoma and 25.6% had squamous cell carcinoma. Conclusion: It was observed that the proportion of females diagnosed with primary lung cancer is increasing. Patients get diagnosed at a later stage of the disease, which calls for screening and early detection of lung cancer. As it accounts for the highest mortality among all other cancers, there is high scope for prevention and screening strategies.

Breast screening practices of 35-65 years old women - A cross-sectional survey in Alappuzha, Kerala, India.

BACKGROUND: Enhancing cancer literacy, promoting early detection, and avoiding treatment delays are essential for reducing breast cancer mortality and ensuring a good quality of life among women in less developed countries. The present paper describes the breast screening practices of women in the Alappuzha district of Kerala state, India. MATERIALS AND METHODS: A multi-stage cluster sampling method was used to select study participants. Data were collected using a structured questionnaire, entered using Kobo Toolbox, and analyzed using IBM SPSS Statistics-25 for Windows. The proportions of women who practiced breast examinations were estimated with 95% confidence intervals. The Chi-square test was used to test the associations, and binary logistic regression was used to estimate odds ratios. RESULTS: Among 320 women, 55% were less than 50 years old, 45% had higher secondary education or above, and six were already diagnosed with breast cancer (1.9%, 95% CI: 0.4%-3.4%). Of the 314 women, 73.2% were practicing breast self-examination (95% CI: 68.4%-78.1%), and 25.2% ever attended clinical breast examination (95% CI: 20.4%-30.0%). Working/retired/self-employed women with higher secondary education and above had almost 10 times higher odds (OR = 10, 95% CI: 3.35-29.86) of practicing breast self-examination (BSE) compared to homemakers or women working under rural employment schemes with a low level of education. CONCLUSION: A higher percentage of women practicing BSE and clinical breast examination (CBE) in the present study indicates that women in this population are more concerned about breast cancer. Women should be educated more on the symptoms and risk factors, the proper ways of practicing BSE, and the importance of consulting a health practitioner for CBE. Also, it is crucial to ensure that awareness and screening programs reach marginalized women.

The Impact of Time to Reperfusion on Recanalization Rates and Outcome After Mechanical Thrombectomy: A Single Center Experience.

Background: Timely and effective recanalization to salvage the penumbra is the main determinant of outcome in acute ischemic strokes. Randomized controlled trials on late window mechanical thrombectomy (MT) have proved its safety and efficacy upto 24 h after stroke onset. We looked at the impact of time to reperfusion on vessel recanalization rates and short-term outcome in patients undergoing MT for large vessel occlusion. Methods: The clinical, imaging, and outcome of all patients undergoing MT upto 24 h from last seen normal was extracted from a prospectively maintained ischemic stroke database from January 2012 till September 2019. Results: There were 145 patients with a mean (SD) age of 58.2 (±14) years. Of them, 28 had wake up/unknown time of onset stroke and 9 presented beyond >360 min. There were 23 vertebrobasilar strokes. Median National Institute of Health Stroke scale score (NIHSS) at admission was 16.4 (Inter quartile range (IQR) 12-21). CT-Alberta Stroke program early CT score (CT-ASPECTS) was excellent (8-10) in 39 (31.6%) and fair (5-7) in 77 (63.6%) patients in anterior circulation strokes. About 25% underwent bridging therapy. Recanalization rates did not differ between those presenting early (<6 h) versus wake up strokes and late presenting patients (81.79% vs 71.9%). Symptomatic Intracerebral hemorrhage (ICH) occurred in 5%. At 3 months, excellent outcome (modified rankin scale <2) was observed in 28.9%. While Admission NIHSS remained strong predictor of poor outcome at 3 months, delay in presentation did not impact MT outcome (37.5% vs 45.79% and P = 0.460). Conclusions: The recanalization rates were similar in patients irrespective of the time to reperfusion from stroke onset. The functional outcome was not inferior in late presenters selected by advanced imaging.

Dysphagia Continues to Impact Recovery at One Year After Stroke-An Observational Study.

OBJECTIVES: Dysphagia is one of the most common medical complication after acute stroke, which can impact hospital stay and discharge outcome. Here we sought to study the predictors and 1 year outcome of patients with acute post stroke dysphagia. METHODS: Single centre hospital based observational study of all acute ischemic stroke patients who had undergone formal swallow assessment within 24 hours of admission with a 1 year completed follow-up were recruited by screening of medical records. Clinical, imaging and swallow assessment details were extracted as per proforma. 3 month and 1 year outcome were assessed using modified Rankin scale. Correlations were made with clinical and imaging findings, in hospital worsening and dysphagia at discharge with short and long term functional outcome. RESULTS: We had 469 patients included in our study, with a mean age 61. 04(±19. 09) years and median NIHSS 9. 52(IQR 4). 56. 75% of AIS patients had some degree of dysphagia at admission. We found that admission stroke severity and in-hospital worsening were independently predictive of severe swallow dysfunction at discharge. At 3-4 weeks after stroke, only 20.27% of the patients with moderate-severe dysphagia at baseline has persistent swallow deficits requiring modification of feeds. Dysphagia continued to have a significant association with outcome at 1 year, independent of admission stroke severity. CONCLUSIONS: Majority of patients with acute post stroke dysphagia recover well within 3-4 weeks after stroke. Patients with post stroke dysphagia had more in hospital neurological worsening. Post stroke dysphagia continued to have an impact on functional outcome up to 1 year after stroke.

Status of cancer screening in India: An alarm signal from the National Family Health Survey (NFHS-5).

Background: Cancer is often detected much later to its onset, resulting in poor prognosis. This makes cancer the second most common cause of death globally. Looking for cancers much before any symptoms occur is termed "cancer screening" and is a powerful strategy for prevention, early diagnosis, and better management of several cancers. This paper examines the status of cancer screening in India from the National Family Health Survey (NFHS)-5 report for the period of 2019-2021. Methods: Secondary data on participation in screening for cervical, breast, and oral cancer were extracted from the NFHS-5 report. Participation status for all the above cancer types is represented as percentages and compared across 28 states and eight union territories in India. Results: The percentages of women who have ever undergone cervical, breast, and oral cavity screening were 1.9%, 0.9%, and 0.9%, respectively. About 1.2% of men participated in oral cavity screening. The highest percentage of cervical and breast cancer screening participation was reported in Tamil Nadu (9.8% and 5.6%, respectively), followed by Puducherry (7.4% and 4.2%) and Mizoram (6.9% and 2.7%). Andaman and Nicobar Islands reported the highest oral cancer screening among women (10.1%) while Andhra Pradesh (6.3%) reported the highest participation among men. Conclusion: Cancer screening participation in India is extremely inadequate and calls for the immediate attention of national and state governments. Additional efforts are warranted to improve public awareness of cancer screening, and appropriate measures should be implemented to conduct well-organized screening programs across the country to ensure maximum participation.

Consumption of fruits, vegetables and salt in the context of control of type 2 diabetes and hypertension in Kerala, India.

BACKGROUND: Proper diet is necessary to control hypertension and diabetes. This paper describes the combined fruit and vegetable, and salt intake of adults (>=18 years) who were detected to have hypertension or diabetes. METHODS: We analysed the data from a state-wide survey of 12012 adults using the World Health Organization STEPs for NCD risk factor surveillance. We evaluated the recommended intake of fruit and vegetable (>=5 servings/day) and salt (<5 gm/day) across participants divided into four strata, and the probabilities were also estimated using the fitted multiple binary logistic regression models. RESULTS: Overall, 13.9% (95%CI: 12.2%-15.9%) and 29.4% (95%CI: 28%-30.8%) of participants consumed the recommended level of fruit and vegetable, and salt, respectively. Adjusted odds ratios were not significantly different across the four strata based on the status of treatment and control of diabetes or hypertension. The likelihood of following the recommended fruit and vegetable intake was highest for 50-69-year-old females with above high school education, obese, under treatment for diabetes or hypertension, and had normal values of FBS and BP (0.28). The likelihood for recommended salt intake was highest for 50-69-year-old males with above high school education and had normal BMI, under treatment for diabetes or hypertension, and had normal values of FBS and BP (0.69). CONCLUSION: The status of diabetes or hypertension did not show considerable influence in the fruit, vegetable, and salt intake of adults in general. A detailed exploration of the accessibility and acceptability of such recommended intakes in the Kerala context is warranted.

STIL Endows Oncogenic and Stem-Like Attributes to Colorectal Cancer Plausibly by Shh and Wnt Signaling.

The discovery of a potent gene regulating tumorigenesis and drug resistance is of high clinical importance. STIL is an oncogene; however, its molecular associations and role in colorectal oncogenesis are unknown. In this study, we have explored the role of STIL gene in tumorigenesis and studied its molecular targets in colorectal cancer (CRC). STIL silencing reduced proliferation and tumor growth in CRC. Further, STIL was found to regulate stemness markers CD133 and CD44 and drug resistant markers thymidylate synthase, ABCB1, and ABCG2 both in in-vitro and in-vivo CRC models. In addition, high expression of STIL mRNA was found to be associated with reduced disease-free survival in CRC cases. Interestingly, we observed that STIL-mediated regulation of stemness and drug resistant genes is not exclusively governed by Sonic hedgehog (Shh) signaling. Remarkably, we found STIL regulate ß-catenin levels through p-AKT, independent of Shh pathway. This partially answers Shh independent regulatory mechanism of cancer stem cell (CSC) markers by STIL. Our study suggests an instrumental role of STIL in molecular manifestation of CRC and progression.

Low Bifidobacterium Abundance in the Lower Gut Microbiota Is Associated With Helicobacter pylori-Related Gastric Ulcer and Gastric Cancer.

Helicobacter pylori infection in stomach leads to gastric cancer, gastric ulcer, and duodenal ulcer. More than 1 million people die each year due to these diseases, but why most H. pylori-infected individuals remain asymptomatic while a certain proportion develops such severe gastric diseases remained an enigma. Several studies indicated that gastric and intestinal microbiota may play a critical role in the development of the H. pylori-associated diseases. However, no specific microbe in the gastric or intestinal microbiota has been clearly linked to H. pylori infection and related gastric diseases. Here, we studied H. pylori infection, its virulence genes, the intestinal microbiota, and the clinical status of Trivandrum residents (N = 375) in southwestern India by standard H. pylori culture, PCR genotype, Sanger sequencing, and microbiome analyses using Illumina Miseq and Nanopore GridION. Our analyses revealed that gastric colonization by virulent H. pylori strains (vacAs1i1m1cagA+) is necessary but not sufficient for developing these diseases. Conversely, distinct microbial pools exist in the lower gut of the H. pylori-infected vs. H. pylori-non-infected individuals. Bifidobacterium (belonging to the phylum Actinobacteria) and Bacteroides (belonging to the phylum Bacteroidetes) were present in lower relative abundance for the H. pylori+ group than the H. pylori- group (p < 0.05). On the contrary, for the H. pylori+ group, genus Dialister (bacteria belonging to the phylum Firmicutes) and genus Prevotella (bacteria belonging to the phylum Bacteroidetes) were present in higher abundance compared to the H. pylori- group (p < 0.05). Notably, those who carried H. pylori in the stomach and had developed aggressive gastric diseases also had extremely low relative abundance (p < 0.05) of several Bifidobacterium species (e.g., B. adolescentis, B. longum) in the lower gut suggesting a protective role of Bifidobacterium. Our results show the link between lower gastrointestinal microbes and upper gastrointestinal diseases. Moreover, the results are important for developing effective probiotic and early prognosis of severe gastric diseases.

A Study of the Developing Paediatric Skullbase Anatomy and its Application to Endoscopic Endonasal Approaches in Children.

OBJECTIVE: The sinonasal anatomy in growing children undergoes change in size along with progressive pneumatization, this is of particular significance in endoscopic endonasal surgery. We aim to measure and quantify the sinonasal dimensions in the Indian paediatric population, which are relevant to skull base surgeons. MATERIAL AND METHODS: This is a retrospective radio anatomical study of sinonasal measurements and volumetric analysis of the sphenoid sinus performed on archived CT images of children less than 18 years of age. RESULTS: CT scan images of 110 patients (male, 68; female, 42) were included for the study. The number of patients in each age groups was as follows [0-6 years, 17; 7-9 years, 20; 10-12 years, 27; 13-15 years, 29; 16-18 years, 17]. The distance from the nares to the sphenoid and from the sphenoid to the sella was significantly greater in children of 13-15 years (69.4 ± 5.2 mm) as compared to children less than six years (62.6 ± 6.7 mm) (P < 0.003). The volume of the sphenoid in children between 0 and 6 years was 4641.4 ± 1924.7 mm3. The pneumatized sphenoid volume in the same age group was 1655 ± 1631.1 mm3. In older children between 13 and 15 years, the total volume of sphenoid sinus was 11732.8 ± 2614.4 mm3. The volume of pneumatization in the sphenoid sinus in this group was 6287.5 ± 2157.9 mm3. The total volume of the sphenoid sinus (Pearson coefficient (r) = 0.704, P < 0.001) and the volume of pneumatization of the sphenoid sinus was also seen to have a positive correlation to the age of the child (r = 0.62, P < 0.0001). The narrowest distance between both the internal carotid arteries was seen at the level of the proximal dural ring. In children less than six years of age it was 13.4 ± 2.0 mm, a significant change was seen by the age of 10-12 years where this distance was 15.6 ± 2.2 mm (P = 0.036). CONCLUSION: The sinonasal anatomy shows progressive development between the age of 6 to 15 years after which it plateaus. The pneumatization in young children may be incomplete, which necessitates drilling in the sphenoid sinus. The intercarotid distance was not seen to be a hindrance for endoscopic endonasal surgery. None of the measurements of the skull-base, made in this study appear to restrict endoscopic endonasal surgery in children. However, a meticulous preoperative assessment of the CT scan may be needed for optimal surgical outcome.

Using open-source data to explore distribution of built environment characteristics across Kerala, India.

BACKGROUND: Built environment characteristics in the neighborhood are of utmost priority for a healthy lifestyle in the fast-urbanizing countries. These characteristics are closely linked to the disease burden and challenges in low- and middle-income countries (LMICs), which have been unexplored using open-source data. The present technology offers online resources and open source software that enable researchers to explore built environment characteristics with health and allied phenomena. OBJECTIVES: This article intends to delineate methods to capture available and accessible objective built environment variables for a state in India and determine their distribution across the state. METHODS: Built environment variables such as population density and residential density were collated from the Census of India. Safety from crime and traffic were captured as crime rates and pedestrian accident rates, respectively, acquired from State Crime Records Bureau. Greenness, built-up density, and land slope were gathered from open-source satellite imagery repository. Road intersection density was derived from OpenStreetMap. Processing and analysis differed for each dataset depending on its source and nature. RESULTS: Each variable showed a distinct pattern across the state. Population and residential density were found to be closely related to each other across both districts and subdistricts. They were both positively related to crime rates, pedestrian accident rates, built-up density, and intersection density, whereas negatively related to land slope and greenness across the subdistricts. CONCLUSION: Delineating the distribution of built environment variables using available and open-source data in resource-poor settings is a first in public health research among LMICs. Cost-effectiveness and reproducible nature of open-source solutions could equip researchers in resource-poor settings to identify built environment characteristics and patterns across regions.

Spatial Clusters of Diabetes and Physical Inactivity: Do Neighborhood Characteristics in High and Low Clusters Differ?

This study aims to find spatial clusters of diabetes and physical inactivity among a sample population in Kerala, India, and evaluate built environment characteristics within the high and low spatial clusters. Spatial clusters with a higher and lower likelihood of diabetes and physical inactivity were identified using spatial scan statistic at various radii. Built environment characteristics were captured at panchayat level and 1600 m buffer around participant location using Geographical Information Systems. Comparison of sociodemographic and built environment factors was carried out for participants within high and low spatial clusters using t tests. Ten high and 8 low spatial clusters of diabetes and 17 high and 23 low spatial clusters of physical inactivity were identified in urban and rural areas of Kerala. Significant differences in built environment characteristics were consistent for low spatial clusters of diabetes and physical inactivity in the urban scenario. Built environment characteristics were found to be relevant in both urban and rural areas of Kerala. There is an urgent call to explore spatial clustering of non-communicable diseases in Kerala and undo the one-size-fits-all approach for prevention and control of non-communicable diseases.

Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2, and its role in breast cancer progression.

BACKGROUND: Smurf2 E3 ubiquitin ligase physically associates with and regulate the stability of distinct cellular protein substrates. The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. The aim of this study was to investigate whether the interaction between Smurf2 and CNKSR2 has any significant role in the post transcriptional regulation of CNKSR2 expression in breast cancer. METHODS: Here we demonstrate a novel interaction of CNKSR2 with Smurf2 by co-immunoprecipitation, indirect immunofluorescence studies, and surface plasmon resonance (SPR) analysis, which can ubiquitinate, but stabilize CNKSR2 by protecting it from proteasome mediated degradation. RESULTS: CNKSR2 protein levels were significantly increased upon forced overexpression of Smurf2, indicating the role of Smurf2 in regulating the stability of CNKSR2. Conversely, Smurf2 knockdown resulted in a marked decrease in the protein level expression of CNKSR2 by facilitating enhanced polyubiquitination and proteasomal degradation and reduced the proliferation and clonogenic survival of MDA-MB-231 breast cancer cell lines. Tissue microarray data from 84 patients with various stages of mammary carcinoma, including (in order of increasing malignant potential) normal, usual hyperplasia, fibrocystic changes, fibroadenoma, carcinoma-in-situ, and invasive ductal carcinoma showed a statistically significant association between Smurf2 and CNKSR2 expression, which is also well correlated with the ER, PR, and HER2 status of the tissue samples. A comparatively high expression of Smurf2 and CNKSR2 was observed when the expression of ER and PR was low, and HER2 was high. Consistently, both Smurf2 and CNKSR2 showed an integrated expression in MCF10 breast progression model cell lines. CONCLUSIONS: Altogether, our findings reveal that Smurf2 is a novel positive regulator of CNKSR2 and suggest that Smurf2-CNKSR2 interaction may serve as a common strategy to control proliferation of human breast cancer cells by modulating CNKSR2 protein stability.

Lack of association of mirSNP rs11174811 in AVPR1A gene with arterial blood pressure and hypertension in South Indian population.

Epigenetic regulation of arterial blood pressure mediated through mirSNPs in renin-angiotensin aldosterone system (RAAS) genes is a less explored hypothesis. Recently, the mirSNP rs11174811 in the 3'UTR of the AVPR1A gene was associated with higher arterial blood pressure in a large study population from the Study of Myocardial Infarctions Leiden (SMILE). The aim of the present study was to replicate the association of mirSNP rs11174811 with blood pressure outcomes and hypertension in a south Indian population. Four hundred and fifteen hypertensive cases and 416 normotensive controls were genotyped using a 5' nuclease allelic discrimination assay. Logistic regression was used to test the association of mirSNP rs11174811 with the hypertension phenotype. Censored normal regression was used to test the association of the polymorphism with continuous blood pressure outcomes such as systolic and diastolic blood pressure. The mirSNP rs11174811 did not show any significant association with hypertension. The adjusted odds ratio was 1.02, with 95% CI of 0.72 to 1.45 (p = 0.909). The mean systolic and diastolic blood pressure values were not significantly different across the three genotypic groups, between hypertensives and normotensives, or when stratified by gender. Despite having a similar minor allele frequency (MAF) of 14.5% compared with the SMILE cohort, our results did not support an association of the mirSNP rs11174811 with the hypertension phenotype or with continuous blood pressure outcomes in the south Indian population.

Folate, vitamin B12, homocysteine and polymorphisms in folate metabolizing genes in children with congenital heart disease and their mothers.

BACKGROUND/OBJECTIVES: The objective of the study was to assess the role of variations in serum folate, vitamin B12, homocysteine and the presence of genetic polymorphisms as risk factors for congenital heart disease (CHD) in children. SUBJECTS/METHODS: A total of 32 children with CHD, and their mothers and 32 normal children and their mothers formed the study and control groups, respectively. Serum folate, vitamin B12 and homocysteine as well as genetic polymorphisms MTHFR C677→︀T, MTHFR A1298→︀C, MTR A2756→︀G and MTRR A66→︀G were assessed. RESULTS: Low serum folate and genetic polymorphisms MTHFR C677→︀T and MTRR A66→︀G among children and their mothers and high homocysteine among mothers were noted as risk factors for CHD (P<0.05). Vitamin B12 levels were normal and showed no association. Presence of MTHFR C677→︀T and MTRR A66→︀G, both concurrently among children as well as mothers and simultaneously among mother-child pairs, showed several fold increase in the risk for CHD. On multivariate analysis, the risk factors noted for CHD were presence of MTHFR C677→︀T among children and their mothers and MTRR A66→︀G among mothers. Analyses for nutrient-gene interaction revealed significant associations between low serum folate and high serum homocysteine levels, and the presence of selected genetic polymorphisms. CONCLUSIONS: Low serum folate, high homocysteine and presence of selected genetic polymorphisms among children and their mothers were noted as risk factors for CHD. Nutrient-gene interaction being a modifiable risk factor, the study recommends the use of peri-conceptional folate supplementation with vitamin B12 sufficiency for primary prevention of CHD.

Evaluating genomic DNA extraction methods from human whole blood using endpoint and real-time PCR assays.

The extraction of genomic DNA is the crucial first step in large-scale epidemiological studies. Though there are many popular DNA isolation methods from human whole blood, only a few reports have compared their efficiencies using both end-point and real-time PCR assays. Genomic DNA was extracted from coronary artery disease patients using solution-based conventional protocols such as the phenol-chloroform/proteinase-K method and a non-phenolic non-enzymatic Rapid-Method, which were evaluated and compared vis-a-vis a commercially available silica column-based Blood DNA isolation kit. The appropriate method for efficiently extracting relatively pure DNA was assessed based on the total DNA yield, concentration, purity ratios (A260/A280 and A260/A230), spectral profile and agarose gel electrophoresis analysis. The quality of the isolated DNA was further analysed for PCR inhibition using a murine specific ATP1A3 qPCR assay and mtDNA/Y-chromosome ratio determination assay. The suitability of the extracted DNA for downstream applications such as end-point SNP genotyping, was tested using PCR-RFLP analysis of the AGTR1-1166A>C variant, a mirSNP having pharmacogenetic relevance in cardiovascular diseases. Compared to the traditional phenol-chloroform/proteinase-K method, our results indicated the Rapid-Method to be a more suitable protocol for genomic DNA extraction from human whole blood in terms of DNA quantity, quality, safety, processing time and cost. The Rapid-Method, which is based on a simple salting-out procedure, is not only safe and cost-effective, but also has the added advantage of being scaled up to process variable sample volumes, thus enabling it to be applied in large-scale epidemiological studies.

Circulating Thrombotic Risk Factors in Young Patients with Coronary Artery Disease Who Are on Statins and Anti-platelet Drugs.

Thrombotic risk factors may contribute to premature coronary artery disease (CAD), in addition to the conventional risk factors. There is paucity of data on studies evaluating the role of thrombotic factors in premature CAD in Indian patients. Thus a case-control study was performed to evaluate the role of thrombotic and atherogenic factors in young patients with angiographically proven CAD who are on treatment with statins and anti-platelet drugs. 152 patients (≤55 years) with angiographically proven CAD and 102 asymptomatic controls were recruited. Clinical and biochemical data were obtained in both groups. Blood levels of thrombotic factors-fibrinogen, antithrombin-III, tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-Willebrand factor (v-WF), lipoprotein(a) [Lp(a)] and homocysteine were analyzed. Patients had high levels of conventional CAD risk factors (diabetes mellitus, smoking, hypertension, dyslipidemia and positive family history) compared to controls. Logistic regression analysis revealed that low antithrombin-III (odds ratio/OR 11.2; 95 % confidence interval/CI 2.29-54.01), high fibrinogen (OR 6.04; 95 % CI 1.09-33.21) and high Lp(a) (OR 4.54; 95 % CI 0.92-22.56), as important, independent risk factors in patients. PAI-1(OR 0.15; 95 % CI 0.03-0.69) levels were significantly lower in patients. But other thrombotic risk factors studied (t-PA, v-WF and homocysteine) were comparable among patients and controls. The treatment using statins and anti-platelet drugs might be contributing to the control of some of the thrombotic risk factors. The strategies aiming at lowering the levels of thrombotic risk factors along with conventional risk factors may be useful in primary and secondary prevention of CAD.

Risk of invasive cancer among women visually screened and colposcopy triaged by trained nurses in rural South India.

OBJECTIVE: To estimate the long-term risk of cervical cancer among women screened by visual inspection with acetic acid (VIA) and to evaluate the benefit of additional colposcopy triage in rural south India. METHODS: A retrospective analysis was conducted among 31 343 women who had undergone VIA at Dindigul district, India between January 1, 2000, and August 5, 2003, as part of a randomized screening trial. Women with positive VIA test results were offered colposcopy triage by trained nurses. Cervical cancer incidence data during follow-up (January 1, 2000, to December 31, 2012) were obtained from a regional cancer registry. RESULTS: Among 3021 screen-positive women free of cancer at baseline, 2974 women underwent colposcopy; colposcopic abnormalities suggestive of precancerous lesions were detected among 2792 of these women (93.9%). Compared with the women with negative VIA screening results, the hazard ratio (HR) of cervical cancer during follow-up among the VIA-positive women without colposcopic abnormalities was 6.5 (95% confidence interval [CI], 1.6-27.1). The risk was similar among VIA-positive women with colposcopic abnormalities but without histological confirmation (HR5.2; 95% CI, 1.9-14.6). CONCLUSION: The high risk of cancer among women without colposcopic abnormalities who tested positive by VIA suggested that screening without triage is potentially effective.

Forkhead box C2 promoter variant c.-512C>T is associated with increased susceptibility to chronic venous diseases.

Chronic venous disease (CVD) is one of the most prevalent yet underrated disorders worldwide. High heritability estimates of CVD indicate prominent genetic components in its etiology and pathology. Mutations in human forkhead box C2 (FoxC2) gene are strongly associated with valve failure in saphenous and deep veins of lower extremities. We explored the association of genetic variants of FoxC2 as well as FoxC2 mRNA and protein expression levels with CVD of lower limbs. We systematically sequenced the single coding exon, 5' and 3' flanking regions of FoxC2 gene in 754 study subjects which includes 382 patients with CVD and 372 healthy subjects. Four novel and three reported polymorphisms were identified in our cohort. Three variants in 5' flanking region and one in 3' flanking region of FoxC2 gene were significantly associated with CVD risk. FoxC2 mRNA in vein tissues from 22 patients was 4±1.42 fold increased compared to saphenous veins from 20 normal subjects (p<0.01). FoxC2 protein was also significantly upregulated in varicose veins compared to control samples. The c.-512C>T (rs34221221: C>T) variant which is located in the FoxC2 putative promoter region was further analyzed. Functional analysis of c.-512C>T revealed increased mRNA and protein expression in patients with homozygous TT genotype compared to heterozygous CT and wild CC genotypes. Luciferase assay indicated higher transcriptional activity of mutant compared to wild genotype of this variant. These findings suggested that c.-512C>T variant of FoxC2 was strongly associated with susceptibility to CVD and also that this variant resulted in FoxC2 overexpression. To obtain a mechanistic insight into the role of upregulated FoxC2 in varicosities, we overexpressed FoxC2 in venous endothelial cells and observed elevated expression of arterial markers Dll4 and Hey2 and downregulation of venous marker COUP-TFII. Our study indicates altered FoxC2-Notch signaling in saphenous vein wall remodeling in patients with varicose veins.

Transesophageal echocardiographic evaluation of left ventricular systolic and diastolic function in response to 20% mannitol and 3% hypertonic saline infusion in neurosurgical patients undergoing craniotomy.

BACKGROUND: Mannitol and hypertonic saline (HS) are routinely used during craniotomy. Both increase myocardial preload and reduce afterload, and may improve cardiac output. It is not currently known whether this results in an improvement in the global myocardial function. Thus, the aim of this study was to compare the effects of a single equiosmolar bolus of 20% mannitol (5 mL/kg) or 3% HS (5 mL/kg) on the global myocardial function by tissue Doppler-derived myocardial performance index (TD-MPI) in patients undergoing craniotomy. METHODS: Fifty adult patients were included and randomized to receive either mannitol or 3% HS. Transesophageal echocardiography was performed in all patients. Early (E) and late (A) peak mitral inflow velocity, early diastolic mitral annular velocity (E prime), isovolumetric relaxation time (IVRT), ejection time (ET), and isovolumetric contraction time (IVCT) were recorded at baseline and at 15, 30, 60, and 120 minutes after administration of the hyperosmolar solutions. TD-MPI was calculated as IVRT+IVCT/ET. RESULTS: There were no significant differences in the TD-MPI (HS vs. mannitol: 0.43 vs. 0.44 [baseline], 0.45 vs. 0.43 [15 min], 0.44 vs. 0.45 [30 min], 0.47 vs. 0.45 [60 min], 0.45 vs. 0.46 [120 min]), E/A ratio, IVCT, and E/E' either within or between the 2 groups at any time point. IVRT was prolonged in HS group as compared with baseline at 15, 30, and 60 minutes postinfusion. ET was decreased in both the groups at 120 minutes postinfusion. Neither of these altered the TD-MPI. CONCLUSIONS: Equiosmolar administration of 20% mannitol and 3% HS did not show any difference in global myocardial performance as measured by TD MPI.