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One of the most frequently used governing equations underpinning engineering flow analysis is the renowned Navier–Stokes (NS) equation. Several references regarding the derivation of equation of motion in Cartesian coordinates are available in standard textbooks. However, derivation of above equation in rotational frame is missing in literatures. Flow analysis using NS equation in rotational frame is a prerequisite for analysis of various engineering problems like rotational flow dynamics in chemical reactors, lubricating oil behavior in various rotating machines, electrolyte flow behavior in electrochemical reactors with rotating electrodes, etc. Systematic understanding of each terms in the equation is essential to develop a suitable governing mathematical model of any physical flow problem with various level of complexities. This is possible only if same can be derived from fundamentals, detailing terms behind the equation. A systematic approach is made here to derive NS equation in rotational frame from basic Cartesian form.

Environmental pollution is increasing worldwide due to population and industrialization. Among the various forms of pollution, water pollution poses a significant challenge in contemporary times. In this study, we synthesized CuO-decorated montmorillonite K30 (MK30) nanosheets via a simple ultrasonication technique. The structural, morphological, compositional, and optical properties of the synthesized nanocomposites were evaluated using advanced instrumentation techniques. The morphology of CuO was cubic and cubic CuO evenly designed on the MK30, which was proved by Field Emission Scanning Electron Microscopy (FESEM). The adsorption photocatalytic activity of the synthesized cubic CuO/MK30 composites was examined through the degradation of MB under visible light irradiation. The apparent reaction rate constant of 20% CuO/MK30 was 12.5 folds higher than that of CuO. These conditions included a catalyst dosage ranging from 5 to 15 mg, a pH level ranging from to 3-11, and a pollutant concentration ranging from 5 to 20 mg/L. The optimal conditions for MB dye removal were determined using response surface methodology (RSM). A scavenger study of the composite was conducted and verified that • O 2 - and • OH radicals play an important role in the degradation process. This investigation addressed the process of adsorption and potential removal pathways, with a particular emphasis on the role of functional groups. The environmentally friendly CuO/MK30 nanocomposites exhibited potential as photocatalysts for efficiently absorbing and degrading MB dye and TC drug pollutants. They represent promising candidates for the treatment of industrial wastewater, aiming to mitigate the environmental threats posed by organic pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Live single-cell metabolomic studies encounter inherent difficulties attributed to the limited sample volume, minimal compound quantity, and insufficient sensitivity in the Mass Spectrometry (MS) method used to obtain single-cell data. However, understanding cellular heterogeneity, functional diversity, and metabolic processes within individual cells is essential. Exploring how individual cells respond to stimuli, including drugs, environmental changes, or signaling molecules, offers insights into biology, oncology, and drug discovery. Efficient release of cell contents (lysis) is vital for accurate metabolite detection at the single-cell level. Despite this, traditional approaches in live single cell metabolomics methods do not emphasize efficient lysis to prevent sample dilution. Instead, current live single cell metabolomics methods use direct infusion to introduce the cell into the mass spectrometry without prior chromatographic separation or a lysis step, which adversely affects sensitivity and metabolic coverage., Results: To address this, we developed an integrated single-cell electrical lysis and nano spray (SCEL-nS) platform coupled to an Orbitrap MS capable of efficiently lysing a single cell after being sampled with specially manufactured micropipettes. Lysis efficiency was validated by comparing live cell stain fluorescent intensities of intact and electrically lysed cells through microscopy imaging. The SCEL-nS platform successfully induced the breakdown of a single cell, significantly reducing the live cell stain's fluorescent intensity indicating cell membrane breakdown. Additionally, SCEL-nS was validated by measuring single cells spiked with the anti-cancer drug tamoxifen by MS. SCEL-nS use resulted in statistically significant increase in the peak measured by the method compared to the traditional non-lysis method., Significance: Overall, our results demonstrate that the newly incorporated SCEL-nS platform achieved higher sensitivities compared to traditional live single cell analysis methods., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Anterior pituitary dysfunction is one of the major causes of disability and morbidity in patients suffering from traumatic brain injury (TBI). The present study was undertaken to evaluate the incidence of anterior pituitary dysfunction in cases of moderate and severe TBI, its value in long-term prognostication, and the factors that predispose to a higher incidence of anterior pituitary dysfunction in acute and chronic phases., Methods: This was a prospective cohort study wherein 216 patients with moderate and severe TBI were evaluated within 72 hours of TBI (acute phase) and at 6 months (chronic phase)., Results: At 6 months, out of the 216 patients, 95 patients had expired and 35 patients were lost to follow-up. The remaining 86 patients were evaluated at 6 months. In the acute phase, hypopituitarism was seen in 82.4% patients, thyroid axis deficiency was seen in 57.4% patients, gonadal axis deficiency in 54.2% patients, and adrenal axis deficiency in 13.8% patients. In the chronic phase, hypopituitarism was seen in 59.3% patients, thyroid axis deficiency was seen in 24.4% patients, gonadal axis deficiency in 32.6% patients, and adrenal axis deficiency in 23.3% patients. Patients with thyroid axis deficiency at admission had significant association with a bad modified Rankin Scale score at 6 months., Conclusions: Thyroid and gonadotropin axes were most commonly affected and deficiency of at least 1 axis was found in 82.4% patients in the acute phase and 59.3% in the chronic phase. Thyroid axis deficiency had a negative impact on prognosis in post-TBI patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Tuberculosis is an infectious disease responsible for a significant cause of ill health. According to the WHO global tuberculosis report 2021. 9.9 million cases fell sick with TB in 2020. Significantly, the prevalence of tuberculosis in India is 25%., Objective: To analyze the prevalence of tuberculosis in the suburban areas of the metropolitan city in South India. To analyze the serological marker and prognosis of tuberculosis among males and females. To determine the importance of molecular testing - PCR confirmation on TB after AFB smear., Methods: A retrospective study to analyze 462 patients enrolled by the respiratory medicine department on suspecting pulmonary- 356 (M-264 & F-92) and extra-pulmonary-106 (M-73&F-33) patients and diagnosed Zhiel-Neelsen staining, Mantoux test, Chip-based RT-PCR test, Erythrocyte sedimentation rate, and analyzed serological test such as C-Reactive Protein, Chemiluminescence immune assay., Results: 23 patients were positive in Ziehl-Neelsen staining, 65 were positive in molecular True-Nat PCR test, Mantoux skin test induration in 10 patients, 98 TB Positive patients examined in the serological analysis, 1 & 3 patients reacted in HIV/HBsAg, and HBsAg test respectively, by chemiluminescence immunoassay, 8 PTB and 4 EPTB and 47 non-TB patients were positive in C-reactive protein, 46 TB and 94 non-TB patients detected abnormal values out of these 160 patients in ESR test., Conclusion: The Prevalence of tuberculosis is significantly rising, especially in the middle-aged population. The rapid molecular diagnostics to detect TB are highly sensitive and specific. Serological markers are essential for the analysis of disease prognosis and need to focus on the guidance of DOTS and RNTCP to End TB., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

It is well established that exposure to ambient air pollution affects human health. A majority of literature concentrated on health effects of air pollution in high income countries. Only fewer studies analyzing health effects of air pollution in Low- and Middle-Income Countries (LMICs) are available. To bridge this gap in literature, this study investigated short term and long-term health impacts of ambient air pollutants focussed in LMICs. We evaluated Total Non-accidental mortality, Respiratory Mortality, Stroke Mortality, Cardio-vascular Mortality, Chronic Obstructive Pulmonary Disease (COPD), Ischemic Heart Disease (IHD) and Lung Cancer Mortality in LMICs particularly. Random Effects Model was utilised to derive overall risk estimate. Relative Risk (RR) estimates per 10 μg/m 3 was used as input for model. Subgroup and Sensitivity Analysis by Design and Country was conducted. A total of 152 studies were included for quantitative analysis. We found positive associations between pollutants and Total Non-accidental mortality for PM 10 ((RR:1.0043-1.0036), p < 0.0001), NO 2 (RR:1.0222 (1.0111-1.0336), p < 0.0001), SO 2 (RR:1.0107 - (1.0073-1.0140), p < 0.0001), O 3 (RR: 1.0038 (1.0023-1.0053), p < 0.0001) and PM 2.5 (RR: 1.0048 (1.0037-1.0059), p < 0.0001) for every 10 μg/m 3 increase. We found positive association between Long-term exposure to PM 10 and Total Non-accidental mortality (RR: 1.0430 (1.0278-1.0583), p < 0.0001) We also found statistically significant positive associations between pollutants and Cardiorespiratory and Cardiovascular morbidity. The positive associations persisted when analysed amongst sub-groups. However, the high heterogeneity amongst studies persisted even after performing sub-group analysis. The study has found statistically significant positive associations between short-term and long-term exposure to Ambient air pollution with various health-outcome combinations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this study, zeolite sodalite SOD (50NaO 2 :Al 2 O 3 :5SiO 2 ), zeolite LTA (2NaO 2 :Al 2 O 3 :1.926SiO 2 ) and zeolite FAU (16NaO 2 :Al 2 O 3 :4SiO 2 ) of different structures were synthesized successfully through simple conventional hydrothermal crystallization technique without using any template agent. Morphological analysis of three different types of zeolites revealed that the samples exhibit three different shapes such as the "Raspberry-like", "Dice" cube like and "Octahedral" shaped morphology respectively. The thermal stability was found to be about 4.8%, 14.6% and 20.5% for the synthesized zeolites SOD, LTA and FAU respectively. From the N 2 adsorption-desorption studies, it was observed that adsorption types IV and I correspond to the synthesized samples. CO 2 adsorption by the synthesized zeolite SOD, LTA and FAU were examined in the pressure range from 0 to 101.325 kPa at a constant temperature of 297.15 K. The highest adsorption capacity of 3.7 mmol/g was obtained for zeolite FAU. The synthesized zeolite was studied using a nonlinear regression curve fit to determine the adsorption isotherm model using Langmuir and Freundlich isotherm model. It has been found that the synthesized zeolites have a large electric field gradient due to which they can strongly adsorb quadrupole of CO 2 molecules., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Amivantamab, an epidermal growth factor receptor (EGFR)-c-Met bispecific antibody, targets activating/resistance EGFR mutations and MET mutations/amplifications. In the ongoing CHRYSALIS study (ClinicalTrials.gov Identifier: NCT02609776), amivantamab demonstrated antitumor activity in patients with non-small cell lung cancer harboring EGFR exon 20 insertion mutations (ex20ins) that progressed on or after platinum-based chemotherapy, a population in which amivantamab use has been approved by the US Food and Drug Administration. This bridging study clinically validated two novel candidate companion diagnostics (CDx) for use in detecting EGFR ex20ins in plasma and tumor tissue, Guardant360 CDx and Oncomine Dx Target Test (ODxT), respectively. From the 81 patients in the CHRYSALIS efficacy population, 78 plasma and 51 tissue samples were tested. Guardant360 CDx identified 62 positive (16 negative), and ODxT identified 39 positive (3 negative), samples with EGFR ex20ins. Baseline demographic and clinical characteristics were similar between the CHRYSALIS-, Guardant360 CDx-, and ODxT-identified populations. Agreement with local PCR/next-generation sequencing tests used for enrollment into CHRYSALIS demonstrated high adjusted negative (99.6% and 99.9%) and positive (100% for both) predictive values with the Guardant360 CDx and ODxT tests, respectively. Overall response rates were comparable between the CHRYSALIS, Guardant360 CDx, and ODxT populations. Both the plasma- and tissue-based diagnostic tests provided accurate, comprehensive, and complementary approaches to identifying patients with EGFR ex20ins who could benefit from amivantamab therapy., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Aims: The impact of behavioural risk factors on the metabolic syndrome has not been well understood by the researchers. This information is important to the policymakers for developing effective strategies and implement relevant policies or programs. Hence, we undertook this meta-analysis to estimate the effect of behavioural risk factors on the burden of metabolic syndrome., Data Synthesis: We conducted a search in the databases, such as PubMed Central, EMBASE, MEDLINE, and Cochrane library, and search engines, such as ScienceDirect and Google Scholar, from inception until March 2021. We used the Newcastle-Ottawa Scale (NOS) to assess the quality of published studies. We carried out a meta-analysis with random-effects model and reported pooled odds ratio (OR) with 95% confidence interval (CI). In total, we analysed 30 studies with 41,090 participants. The majority of the studies had good to satisfactory quality as per NOS. Physical activity had a statistically significant association with the prevalence of metabolic syndrome (pooled OR = 1.57; 95%CI: 1.28 to 1.93, I 2  = 91%). However, smoking (pooled OR = 0.96; 95%CI: 0.75 to 1.23, I 2  = 90.5%) and alcohol (pooled OR = 1.00; 95%CI: 0.75 to 1.33, I 2  = 90.8%) did not reveal a statistically significant association with the burden of metabolic syndrome., Conclusion: Physical inactivity was found to be a significant risk factor for metabolic syndrome. Given the evidence, it is important that the clinicians and policymakers are alike to recommend regular physical activity among the patients and general population., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Raw municipal wastewater from five wastewater treatment plants representing the vast majority of the Qatar population was sampled between the third week of June 2020 and the end of August 2020, during the period of declining cases after the peak of the first wave of infection in May 2020. The N1 region of the SARS-CoV-2 genome was used to quantify the viral load in the wastewater using RT-qPCR. The trend in Ct values in the wastewater samples mirrored the number of new daily positive cases officially reported for the country, confirmed by RT-qPCR testing of naso-pharyngeal swabs. SARS-CoV-2 RNA was detected in 100% of the influent wastewater samples (7889 ± 1421 copy/L - 542,056 ± 25,775 copy/L, based on the N1 assay). A mathematical model for wastewater-based epidemiology was developed and used to estimate the number of people in the population infected with COVID-19 from the N1 Ct values in the wastewater samples. The estimated number of infected population on any given day using the wastewater-based epidemiology approach declined from 542,313 ± 51,159 to 31,181 ± 3081 over the course of the sampling period, which was significantly higher than the officially reported numbers. However, seroprevalence data from Qatar indicates that diagnosed infections represented only about 10% of actual cases. The model estimates were lower than the corrected numbers based on application of a static diagnosis ratio of 10% to the RT-qPCR identified cases, which is assumed to be due to the difficulty in quantifying RNA losses as a model term. However, these results indicate that the presented WBE modeling approach allows for a realistic assessment of incidence trend in a given population, with a more reliable estimation of the number of infected people at any given point in time than can be achieved using human biomonitoring alone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, the removal of ibuprofen and gemfibrozil by chlorination, ozonation and a combination of ozone/hydrogen peroxide (O 3 /H 2 O 2 ) advanced oxidation process (AOP) from treated sewage effluent (TSE) has been investigated. The removals were evaluated as single components and in binary systems at different oxidant dosages. Chlorination showed insignificant removal for both pharmaceuticals, while ozonation and O 3 /H 2 O 2 achieved significant removals for both ibuprofen and gemfibrozil. The highest removal efficiency of ibuprofen achieved with ozonation and O 3 /H 2 O 2 in TSE was 80% at 1.5 mg/L ozone dosage (0.27 mg O 3 /mg DOC) within 5 min contact time and was not increased at extended times as the ozone residual approached zero in 5 min. For gemfibrozil, complete removals were achieved at ozone dosages of 1 and 1.5 mg/L by both ozonation and O 3 /H 2 O 2 within 30 s. The rate constants obtained from the second order kinetics study were almost similar for the binary and single component tests, however, the degradation of ibuprofen was around four times faster by O 3 /H 2 O 2 with a rate constant of 9 × 10 4 M -1  s -1 in comparison to ozone alone. The results in the single component and binary systems were almost similar for gemfibrozil, but noticeably lower removals of ibuprofen were obtained in the binary system showing the higher selectivity and oxidation demand of gemfibrozil. Although O 3 /H 2 O 2 has a higher operation cost, but its capability for faster degradation makes it preferable over ozonation only, as more water can be treated on a daily basis or a smaller treatment plant can be used with lower capital cost, which practically becomes more cost efficient., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Despite reports of a high prevalence of chronic kidney disease (CKD) from the coastal Uddanam region of Andhra Pradesh, India, there are no accurate data on the distribution of kidney function abnormalities and CKD risk factors in this region., Methods: A total of 2419 participants were recruited through multistage cluster random sampling from 67 villages. Serum creatinine and urine protein creatinine ratio were measured using validated methodologies. All abnormal estimated glomerular filtration rate (eGFR) and urine protein creatinine ratio values were reconfirmed after 3 months. A range of sociodemographic factors were evaluated for their association with CKD using Poisson regression., Results: Of 2402 eligible subjects (mean ± SD age, 45.67 ± 13.29 years; 51% female), 506 (21.07%) had CKD (mean ± SD age, 51.79 ± 13.12 years; 41.3% female). A total of 246 (10.24%) had eGFR <60 ml/min/1.73 m 2 , whereas 371 (15.45%) had an elevated urine protein creatinine ratio (>0.15 g/g). The poststratified estimates, adjusted for age and sex distribution of the region for CKD prevalence, are 18.7% (range, 16.4%-21.0%) overall and 21.3% (range, 18.2%-24.4% ) and 16.2% (range, 13.7%-18.8%) in men and women, respectively. Older age, male sex, tobacco use, hypertension, and family history of CKD were independently associated with CKD. Compared with those with higher eGFR, those with eGFR <60 ml/min/1.73m 2 were older, were more likely to be uneducated, manual laborers/farmers, or tobacco users, and were more likely to have hypertension, a family history of CKD, a diagnosis of heart disease, and a lower body mass index. Among those with low eGFR, there was no difference between those with urine protein creatinine ratio <0.15 or >0.15, except a lower frequency of males in the former., Conclusion: We confirmed the high prevalence of CKD in the adult population of Uddanam. The cause was not apparent in a majority. Subjects with a low eGFR with or without elevated proteinuria were phenotypically distinct from those with proteinuria and preserved eGFR. Our data suggest the need to apply a population-based approach to screening and prevention and studies to understand the causes of CKD in this region., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Aim: To define the incidence, presentation, and outcomes of drug-induced Torsades de Pointes (TdP) with intravenous (IV) amiodarone., Methods: From January 2014 to August 2016 a total of 268 patients received IV amiodarone, 142 for ventricular tachycardia, 104 for atrial flutter/fibrillation, and 22 for incessant atrial tachycardia. A uniform dosing of amiodarone to yield 1gm/day was used in all patients., Results: Four of the 268 patients (M:F 1:3) with mean age of 51.25+9.17years developed pause dependent TdP degenerating to VF, after a mean dose of 690+176.63mg, infused over 12+5.88h. The QTc that was 505+9.02ms at the time of TdP normalized to 433.75+6.13ms 48-72h after stopping amiodarone. There was no immediate or late mortality, and patients are well at 5-10 months of follow-up. None of the patients tested positive for LQTS genes., Conclusion: The incidence of drug-induced TdP with IV amiodarone is about 1.5%. Risk factors include female sex, left ventricular dysfunction, electrolyte abnormalities, baseline prolonged QTc, concomitant beta-blocker, and digoxin therapy. Amiodarone induced TdP has favorable prognosis if recognized and treated promptly, and these patients should not receive amiodarone by any route in future., (Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: The T peak - T end interval (the interval from the peak to the end of the T wave), an electrocardiographic marker reflecting transmural dispersion of repolarization, has been used to predict ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death in different clinical settings., Objective: This systematic review and meta-analysis evaluated the significance of the T peak - T end interval in predicting arrhythmic and/or mortality end points., Methods: PubMed, Embase, Cochrane Library, and CINAHL Plus databases were searched through November 30, 2016., Results: Of the 854 studies identified initially, 33 observational studies involving 155,856 patients were included in our meta-analysis. T peak - T end interval prolongation (mean cutoff value 103.3 ± 17.4 ms) was a significant predictor of the arrhythmic or mortality outcomes (odds ratio [OR] 1.14; 95% confidence interval [CI] 1.11-1.17; P < .001). When different end points were analyzed, the ORs were as follows: VT/VF, 1.10 (95% CI 1.06-1.13; P < .0001); sudden cardiac death, 1.27 (95% CI 1.17-1.39; P < .0001); cardiovascular death, 1.40 (95% CI 1.19-1.64; P < .0001); and all-cause mortality, 4.56 (95% CI 0.62-33.68; P < .0001). Subgroup analysis for each disease revealed that the risk of VT/VF or death was highest for Brugada syndrome (OR 5.68; 95% CI 1.57-20.53; P < .01), followed by hypertension (OR 1.52; 95% CI 1.26-1.85; P < .0001), heart failure (OR 1.07; 95% CI 1.04-1.11; P < .0001), and ischemic heart disease (OR 1.06; 95% CI 1.02-1.10; P = 0.001)., Conclusion: The T peak - T end interval is a useful risk stratification tool in different diseases and in the general population., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Chronic kidney disease (CKD) is commonly associated with disturbances in mineral metabolism and bone disease. Bone biopsy is the gold standard in diagnosing mineral bone disorder. Hence the search for non-invasive assessment of bone health gains importance. We undertook to assess the bone health in men with stage 4 and 5 chronic kidney Disease., Methods: We recruited 32 male subjects with Stage 4 and 5 chronic kidney disease and 32 age-matched healthy male controls. 25-hydroxyvitamin D, intact parathyroid hormone, and bone-specific alkaline phosphatase were assayed. Bone mineral density (BMD) was estimated using dual-energy X-ray absorptiometry., Results: CKD is associated with significantly higher levels of bone-specific alkaline phosphatase and intact parathyroid hormone and lower levels of 25-hydroxyvitamin D and bone mineral density, when compared to controls. In the multivariate linear regression model, bone-specific alkaline phosphatase emerged as an independent predictor of reduced BMD. Receiver Operator Characteristic analysis for prediction of reduced BMD in CKD showed both intact parathyroid hormone and bone-specific alkaline phosphatase have significant predicting power., Conclusion: The combination of bone-specific alkaline phosphatase and intact parathyroid hormone has more significant predicting power and is a more reliable index for non-invasive assessment of bone health in men with chronic kidney disease, than either marker when used alone., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: HUTT test is used in evaluation of syncope. Isoprenaline and isosorbide dinitrate are used to increase the sensitivity of the test. These drugs act by different mechanisms. We aimed to compare the results of isoprenaline with isosorbide dinitrate., Methods and Results: We studied 198 subjects referred for HUTT to our institute; those above the age of 35 years were not included in our study, because isoprenaline was not used commonly above this age; thus, only 90 subjects were analyzed. We found that isosorbide dinitrate resulted in more HUTT-positive results than isoprenaline by absolute risk difference of 26%; relative risk for positive isoprenaline was 60%, confidence interval 0.38-0.93, and P value of 0.03. There was no difference in frequency of types of responses, i.e. Type 1, Type 2, and Type 3 between passive testing, isosorbide dinitrate, and isoprenaline, confidence interval 1.53-2.02, and P value 0.71. Time to get positive response was highest for passive testing followed by ISO and ISDN; the mean was 16.85±7.00min, 9.85±5.84min, and 7.00±3.35min, respectively. Statistically, ISDN versus ISO time to get positive response was not significant; P value was 0.074 and 95% confidence interval was -0.28 to 5.98., Conclusions: Isosorbide dinitrate yields more positive HUTT than isoprenaline. The frequencies of type of responses are not different between passive testing, isosorbide dinitrate, and isoprenaline. There is no difference in time taken for positive response between isosorbide dinitrate and isoprenaline. In comparison to isosorbide dinitrate and isoprenaline, passive testing showed longest time for positive response., (Copyright © 2016. Published by Elsevier B.V.)

Background: There is limited data regarding the demographics and type of cardiac implantable electronic device (CIED) in India., Aim: The aim of this survey was to define trends in CIED implants, which included permanent pacemakers (PM), intracardiac defibrillators (ICD), and cardiac resynchronization therapy pacemakers and defibrillators (CRT-P/D) devices in India., Methods: The survey was the initiative of the Indian Society of Electrocardiology and the Indian Heart Rhythm Society. The type of CIED used, their indications, demographic characteristics, clinical status and co-morbidities were collected using a survey form over a period of 1 year., Results: 2117 forms were analysed from 136 centers. PM for bradyarrhythmic indication constituted 80% of the devices implanted with ICD's and CRT-P/D forming approximately 10% each. The most common indication for PM implantation was complete atrio-ventricular block (76%). Single chamber (VVI) pacemakers formed 54% of implants, majority in males (64%). The indication for ICD implantation was almost equal for primary and secondary prevention. A single chamber ICD was most commonly implanted (65%). Coronary artery disease was the etiology in 58.5% of patients with ICD implants. CRT pacemakers were implanted mostly in patients with NYHA III/IV (82%), left ventricular ejection fraction <0.35 (88%) with CRT-P being most commonly used (57%)., Conclusion: A large proportion of CIED implants in India are PM for bradyarrhythmic indications, predominantly AV block. ICD's are implanted almost equally for primary and secondary prophylaxis. Most CRT devices are implanted for NYHA Class III. There is a male predominance for implantation of CIED., (Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

The SCN5A gene encodes for the INa channel implicated in long QT syndrome type-3 (LQTS-type-3). Clinical symptoms of this type are lethal as most patients had a sudden death during sleep. Screening of SCN5A in South Indian cohort by PCR-SSCP analyses revealed five polymorphisms - A29A (exon-2), H558R (exon-12), E1061E and S1074R (exon-17) and IVS25 + 65G > A (exon-25) respectively. In-silico and statistical analyses were performed on all the polymorphisms. Exon-2 of SCN5A gene revealed A282G polymorphism (rs6599230), resulting in alanine for alanine (A29A) silent substitution in the N-terminus of SCN5A protein. Exon-12 showed A1868G polymorphism (H558R - rs1805124) and its 'AA' genotype and 'A' allele frequency were found to be higher in LQTS patients pointing towards its role in LQTS etiology. Two polymorphisms A3378G (E1061E) and the novel C3417A (S1074R) were identified as compound heterozygotes/genetic compounds in exon-17 of SCN5A located in the DIIS6-DIIIS1 domain of the SCN5A transmembrane protein. IVS25 + 65G > A was identified in intron-25 of SCN5A. The 'G' allele was identified as the risk allele. Variations were identified in in-silico analyses which revealed that these genetic compounds may lead to downstream signaling variations causing aberrations in sodium channel functions leading to prolonged QTc. The compound heterozygotes of SCN5A gene polymorphisms revealed a significant association which may be deleterious/lethal leading to an aberrant sodium ion channel causing prolonged QTc.

Background: Magnetic resonance imaging (MRI) can be safely performed in patients with magnetic resonance (MR)-conditional pacemaker systems but remains relatively contraindicated with non-MR-conditional pacemaker systems., Objective: The purpose of this study was to evaluate the safety of MRI without positioning restrictions in patients with an MR-conditional pacemaker and currently a non-MR-conditional Medtronic CapSureFix Novus 5076 lead(s)., Methods: The study randomized 266 patients in a 2:1 ratio to the MRI group (177 patients) or to the control group (89 patients). At 9-12 weeks postimplant, the MRI group underwent MRI at 1.5 T. Primary end points were MRI-related complication-free rate and noninferiority of the MRI group compared to the control group with regard to the proportion of patients with an increase of ≤0.5 V in right atrial (RA) and right ventricular (RV) pacing capture thresholds from immediately before MRI to 1-month after MRI., Results: No MRI-related complications occurred in 156 MRI-scanned patients who were followed through 1-month post-MRI. Differences in the proportion of patients with ≤0.5 V pacing capture threshold changes from pre-MRI to 1-month post-MRI were minimal between the groups for RA (proportions of 100% in both groups; a P value cannot be calculated) and RV leads (proportions of 99.3% in the MRI group and 100% in the control group; noninferiority test, P < .0001). Proportions of patients with acceptable sensing amplitude changes from pre-MRI to 1-month post-MRI were also similar between the 2 groups for RA and RV leads (noninferiority test, P < .0001 and P = .0004, respectively). No arrhythmias occurred during MRI., Conclusion: MRI scans can be performed safely without positioning restrictions in patients with Medtronic CapSureFix Novus 5076 leads connected to an MR-conditional pacemaker., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Prolonged Tpeak-end (the interval from the peak of the T wave to the end of the T wave) and Tpeak-end/QT ratio have been shown to be markers of arrhythmogenesis in various cardiac disorders., Objectives: The purpose of this study was to evaluate the utility of Tpeak-end and Tpeak-end/QT ratio at admission in patients with acute ST-segment elevation myocardial infarction (STEMI) in predicting malignant ventricular arrhythmias., Methods: The study group included 50 patients presenting with STEMI, in whom Tpeak-end and Tpeak-end/QT ratio were measured at admission; these patients were monitored for arrhythmias with a continuous electrocardiogram in the intensive care unit for 48 hours, and 50 healthy individuals acted as controls., Results: The Tpeak-end (0.11 ± 0.04 seconds vs 0.08 ± 0.006 seconds; P < .0010) and Tpeak-end/QT ratio (0.30 ± 0.06 vs 0.21 ± 0.02; P < .001) were prolonged in patients with STEMI. Three patients with STEMI who sustained ventricular fibrillation (VF) within 24 hours of admission had prolonged corrected QT interval (0.39 ± 0.04 seconds vs 0.46 ± 0.13 seconds; P = .019), Tpeak-end (0.10 ± 0.02 seconds vs 0.20 ± 0.11 seconds; P < .001), and Tpeak-end/QT ratio (0.26 ± 0.05 vs 0.41 ± 0.09; P < .001) as compared with patients with STEMI without VF. Tpeak-end > 0.1 seconds and Tpeak-end/QT ratio > 0.3 predicted VF with a sensitivity of 100%. However, the Tpeak-end/QT ratio had a higher specificity (82.9% for Tpeak-end/QT ratio vs 44.7% for Tpeak-end) and accuracy (84% for Tpeak-end/QT ratio vs 48% for Tpeak-end)., Conclusion: Tpeak-end and Tpeak-end/QT ratio are prolonged in patients with STEMI compared with healthy individuals, and Tpeak-end > 0.1 and Tpeak-end/QT ratio > 0.3 predict malignant ventricular arrhythmias within 24 hours of STEMI., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Pure CuO and Zn-doped CuO nanoparticles were synthesized from sol-gel process by reacting copper acetate monohydrate with a urea in distilled water at 80°C. The synthesized Samples were different concentrations but same annealing temperature at 400°C. The obtained samples were characterized by means of UV-visible spectroscopy (UV-vis), X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), Field emission scanning electron microscopy (FE-SEM) and Energy dispersive X-ray spectroscopy (EDS). UV-visible technique used to measure the band gap of the synthesized samples. The XRD spectra of the synthesized samples confirmed the CuO nanoparticles with monoclinic structure. All the functional groups of the pure and doped synthesized samples were investigated by FT-IR analysis. The morphological and elemental estimation of the pure and Zn-doped synthesized samples were examined by FE-SEM with EDS., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Lyme carditis is a known cause of atrioventricular block and in most cases, atrioventricular block is reversible with appropriate antibiotic treatment. The diagnosis can be challenging if the disease is either not suspected, or if the initial cutaneous manifestation of erythema migrans is missed. It is important to diagnose Lyme carditis as the cause of complete heart block if unnecessary pacemaker implantation is to be avoided. We present a 43-year-old male who presented with complete heart block and also ill sustained ventricular tachycardia due to Lyme carditis that reversed completely with antibiotic therapy., (Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: Intestinal immunity induced by oral poliovirus vaccine (OPV) is imperfect and wanes with time, permitting transmission of infection by immunised children. Inactivated poliovirus vaccine (IPV) does not induce an intestinal mucosal immune response, but could boost protection in children who are mucosally primed through previous exposure to OPV. We aimed to assess the effect of IPV on intestinal immunity in children previously vaccinated with OPV., Methods: We did an open-label, randomised controlled trial in children aged 1-4 years from Chinnallapuram, Vellore, India, who were healthy, had not received IPV before, and had had their last dose of OPV at least 6 months before enrolment. Children were randomly assigned (1:1) to receive 0·5 mL IPV intramuscularly (containing 40, 8, and 32 D antigen units for serotypes 1, 2, and 3) or no vaccine. The randomisation sequence was computer generated with a blocked randomisation procedure with block sizes of ten by an independent statistician. The laboratory staff did blinded assessments. The primary outcome was the proportion of children shedding poliovirus 7 days after a challenge dose of serotype 1 and 3 bivalent OPV (bOPV). A second dose of bOPV was given to children in the no vaccine group to assess intestinal immunity resulting from the first dose. A per-protocol analysis was planned for all children who provided a stool sample at 7 days after bOPV challenge. This trial is registered with Clinical Trials Registry of India, number CTRI/2012/09/003005., Findings: Between Aug 19, 2013, and Sept 13, 2013, 450 children were enrolled and randomly assigned into study groups. 225 children received IPV and 225 no vaccine. 222 children in the no vaccine group and 224 children in the IPV group had stool samples available for primary analysis 7 days after bOPV challenge. In the IPV group, 27 (12%) children shed serotype 1 poliovirus and 17 (8%) shed serotype 3 poliovirus compared with 43 (19%) and 57 (26%) in the no vaccine group (risk ratio 0·62, 95% CI 0·40-0·97, p=0·0375; 0·30, 0·18-0·49, p<0·0001). No adverse events were related to the study interventions., Interpretation: The substantial boost in intestinal immunity conferred by a supplementary dose of IPV given to children younger than 5 years who had previously received OPV shows a potential role for this vaccine in immunisation activities to accelerate eradication and prevent outbreaks of poliomyelitis., Funding: Bill & Melinda Gates Foundation.

Background: Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India., Methods: We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109)., Findings: 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product., Interpretation: Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants., Funding: Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Non-Hodgkin Lymphoma (NHL) is a type of hematological malignancy that affects two percent of the overall population in the United States. Tetraspanin CD9 is a cell surface protein that has been thoroughly demonstrated to be a molecular facilitator of cellular phenotype. CD9 expression varies in two human lymphoma cell lines, Raji and BJAB. In this report, we investigated the functional relationship between CD9 and cell proliferation regulated by histone deacetylase (HDAC) activity in these two cell lines. Introduction of CD9 expression in Raji cells resulted in significantly increased cell proliferation and HDAC activity compared to Mock transfected Raji cells. The increase in CD9-Raji cell proliferation was significantly inhibited by HDAC inhibitor (HDACi) treatment. Pretreatment of BJAB cells with HDAC inhibitors resulted in a significant decrease in endogenous CD9 mRNA and cell surface expression. BJAB cells also displayed decreased cell proliferation after HDACi treatment. These results suggest a significant relationship between CD9 expression and cell proliferation in human lymphoma cells that may be modulated by HDAC activity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The uncapped and capped CuO nanoparticles were synthesized by sol-gel process. Ethylene diamine tetra acetic acid (EDTA) used as a capping agent to control the size and morphology of the CuO nanoparticles. Control the nanostructure and optical properties of CuO nanoparticles are deliberate by using capping agent. The obtained samples were characterized by means of UV-Visible spectroscopy (UV-Vis), X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM) along with energy dispersive X-ray spectroscopy (EDS). UV-Visible technique used to measure the band gap of the synthesized samples. The XRD spectra of the synthesized samples confirmed the CuO nanoparticles with monoclinic structure. The occurrences of capping agent have been analyzed by Fourier transform-infrared spectroscopy (FT-IR). The FT-IR study revealed that the transmittance peaks at 501cm(-1) and 592cm(-1) were CuO stretching mode, and 677cm(-1) was CuO monoclinic phase of the uncapped CuO nanoparticles. Further, SEM study find out the morphology of the synthesized samples, where the surface morphology changes occurred with an addition of capping agent. Moreover, the capping mechanism has been discussed based on the chemical reaction between the CuO nanoparticles and the functional groups of the capping agent., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Ocular administration of the beta (β)-adrenergic receptor agonist JP-49b prevents retinopathy-like damage in a preclinical rat model of diabetes. Importantly, JP-49b did not induce characteristic β-adrenergic agonist-related side effects (e.g., left ventricular damage), which led to the hypothesis that JP-49b systemic exposure was minimal following ocular administration. To test this hypothesis, a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to study the preclinical pharmacokinetics of JP-49b in rats. Animals received either a single periocular or intravenous injection of JP-49b (10mg/kg) and plasma and tissue samples were obtained. JP-49b and fenoterol hydrobromide (internal standard, IS) were isolated by liquid-liquid extraction and extracts were analyzed by reversed-phase liquid chromatography on a C18 column using a gradient elution (acetic acid in water and methanol). A triple quadrupole mass spectrometer operating in the positive electrospray ionization mode with multiple reaction monitoring was used to detect JP-49b and IS transitions of m/z 346.4→195.1 and 304.1→134.9. The method was validated for selectivity, linearity, accuracy, and precision in rat vitreous humor, tissue homogenates, and plasma. Following intravenous administration, JP-49b was found to have a rapid clearance (36±5.8L/h/kg), high volume of distribution (244±51.5L/kg) and a terminal half-life of 4.8±1.6h. JP-49b was rapidly absorbed and extensively distributed into ocular tissue following topical administration. However, JP-49b was undetectable in heart tissue 24h after ocular administration. High local drug concentrations coupled with minimal systemic exposure following ocular administration supports further testing of JP-49b as a localized therapy for diabetic retinopathy., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Distribution of heavy metals and its associated oxidative stress, ultrastructure and expression of HSP 70 were studied in varies tissues of Chanos chanos collected from polluted sites compared with the fish collected from less polluted sites of Kaattuppalli Island. The concentrations of copper, lead, zinc, cadmium, manganese and iron were quantified in gills and liver. The results showed marked differences between the two sites as well as significant variations within the tissues. The decreasing trend of metals in the tissues of fish sampled from both polluted and less polluted sites was in the order of Fe>Mn>Zn>Cu>Pb>Cd. Overall, the highest metal concentrations were found in the fish collected from polluted sites. Similarly increase of antioxidant enzymes biomarkers due to heavy metals was also evident in gills and liver of the fish collected from polluted sites. These tissues were further investigated by scanning and electron microscopy and the results were compared with the reference less polluted sites. The presence of large lipid droplets in liver and increase of mucous cells in gills were some of the most noticeable alterations observed and were related to heavy metal contaminants. It is concluded that scanning, ultrastructural and useful of HSP70 biomarkers for heavy metal induced oxidative stress, and demonstrate that precautions need to be taken in polluted sites of Kaattuppalli Island in order to prevent heavy metal pollution that can occur in the future., (© 2013 Elsevier Inc. All rights reserved.)

Objective: To describe the clinicopathologic features of congenital ectropion uvea associated with glaucoma in neurofibromatosis-1 (NF-1)., Design: Retrospective case series., Participants and Controls: Five cases of NF-1 associated with glaucoma, from which enucleated eyes were available, and 2 eye bank eyes used as controls., Methods: The clinical features and courses of these patients were reviewed. Formalin-fixed, paraffin-embedded eyes were examined by light and electron microscopy. Immunohistochemistry using antineurofibromin, anti-glial fibrillary acidic protein, and antivimentin was performed in 3 patients. Gene expression of the mitogen-activated protein kinase (MAPK) signaling pathway was examined in corneal endothelial cells in 1 patient., Main Outcome Measures: Cause of glaucoma in patients with ectropion uvea and NF-1., Results: The age of patients at the time of glaucoma diagnosis ranged from birth to 13 years. Four of the 5 patients had megalocornea and buphthalmos at presentation. Ectropion uvea was noted clinically in 2 patients, but was demonstrated histopathologically in all 5 patients. On histopathologic examination, all patients had varying degrees of angle closure secondary to endothelialization of the anterior chamber angle. Uveal neurofibromas were noted in all patients; anteriorly displaced ciliary processes were noted in 4 of 5 patients who demonstrated ciliary body involvement with neurofibromas. Absence of Schlemm's canal was observed. The endothelial cells lining the closed angle demonstrated positive stain results with the vimentin antibody. Positive antineurofibromin immunolabeling was detected in normal control corneal endothelium, but was absent in corneal endothelium in patients with endothelialization of the angle. Upregulation of genes from the MAPK signaling pathway was demonstrated in the corneal endothelial cells isolated from the NF-1 eyes., Conclusions: Ectropion uvea in NF-1 glaucoma is secondary to endothelialization of the anterior chamber angle and is associated commonly with severe pediatric glaucoma in NF-1 patients. The endothelial cell proliferation may be related to overexpression of the Ras (Rat sarcoma)-MAPK genes in these eyes., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of the study is to investigate the activity and safety of oral talactoferrin (TLF) plus carboplatin and paclitaxel (C/P) in patients with previously untreated stage IIIB/IV non-small cell lung cancer., Methods: Patients (n = 110) were randomly assigned to receive C/P plus either TLF (C/P/T) or placebo (C/P/P). The primary objective of this exploratory study was assessment of confirmed response rate (RR) in the prospectively defined evaluable population with a one-tailed p = 0.05. Secondary objectives included assessment of progression-free survival (PFS), duration of response, overall survival (OS), and safety., Results: The trial met the primary end point of improvement in confirmed RR in the prospectively defined evaluable population. Compared with the C/P/P group, RR increased in the C/P/T group by 18% (29-47%; p = 0.05) and 15% (27-42%; p = 0.08) in the evaluable and intent-to-treat populations, respectively. Compared with the C/P/P group, the C/P/T group had a longer median PFS (4.2 versus 7.0 months), OS (8.5 versus 10.4 months), and duration of response (5.5 versus 7.6 months), although the differences were not statistically significant. Adverse events (AEs) were consistent with C/P therapy. There were fewer total AEs (472 versus 569; two-tailed p = 0.003) and grade 3/4 AEs (78 versus 105; p = 0.05) in the C/P/T group compared with the C/P/P group., Conclusion: TLF, in combination with C/P, demonstrated an apparent improvement in RR, PFS, and OS in patients with previously untreated stage IIIB/IV non-small cell lung cancer and appears to enhance activity without significant additional toxicity. These results need to be confirmed in a phase III trial.

Background: The focal goal of this study is to identify optimal accumulation periods for ALA-induced PpIX in different healthy anatomical sites of human oral cavity and different types of abnormal mucosa to improve the accuracy of the clinical applications such as photodiagnosis and tissue grading., Materials and Methods: Laser-induced fluorescence (LIF) emission spectra, with excitation at 404 nm from a diode laser, were recorded with a miniature fiber-optics spectrometer from 13 anatomical sites of oral mucosa in 15 healthy volunteers and 30 suspicious sites in 15 patients after topical application of 0.4% 5-ALA solution for 15 min. The optimal accumulation time in different anatomical sites of healthy subjects and abnormal tissues were determined by studying the temporal variation in normalized fluorescence intensities (NFI) at 635, 685 and 705 nm., Results and Discussions: In masticatory anatomical locations such as (gingival and hard palate) and in lining mucosa (inner lip, soft palate, floor of mouth, transition to floor of mouth, alveolus and ventral tongue) except vermillion border of lip (VBL) of healthy subjects (designated as group I), it was observed that optimum time for maximum accumulation of PpIX is 90 min. In comparison, for lateral side of tongue (LST) and dorsal side of tongue (DST) tissues (designated as group II), maximum accumulation of PpIX was observed in 150 min of ALA application. For diverse grade lesions of group I mucosa in patients, maximum accumulation of PpIX was observed in 90 min, whereas, in group II mucosa the optimum accumulation time was 150 min as in the case of healthy mucosa. Further, between different grades oral mucosa, maximum variation in NFI take place at these optimal time periods., Conclusions: The determination of the optimum accumulation time of ALA in oral mucosa based on NFI helps to improve the diagnostic contrast and accuracy of oral cancer diagnosis, and to plan appropriate timing for ensuing PDT., ((c) 2010 Elsevier B.V. All rights reserved.)

This article concerns the 20th century saga of Ayurvedic Education up to the current situation, based on a general appreciation of knowledge in Ayurveda. In this light, it considers how to improve quality of teaching and teachers. This is most important, because in education, teachers are the custodians of tradition and knowledge. As those most responsible for maintaining or restoring quality, teachers have very important roles to play. The article also treats 'learning and teaching': who should learn Ayurveda, and how to teach Ayurveda so that it continues from generation to generation, leading to the final area of onsideration, reforms in teaching Ayurveda, and future prospects.

Purpose: To report the prevalence of ocular morbidity in patients with treated multibacillary Hansen's disease (HD) using modern ophthalmic diagnostic techniques in a rural community endemic for HD., Design: Cross-sectional, observation study., Participants: All patients with multibacillary HD who had completed their multidrug therapy and who resided in 4 defined geographical areas in Vellore, Tamil Nadu, India., Methods: All participants underwent a complete eye examination that included slit-lamp examination, esthesiometry, gonioscopy, applanation tonometry, and dilated fundus examination, including a stereobiomicroscopic examination of the fundus at an ophthalmic center set up for that purpose. Glaucoma suspects underwent automated perimetry using a Humphrey Field Analyzer (Humphrey Instruments, San Leandro, CA)., Main Outcome Measures: The prevalence of various ocular disease parameters were reported as mean value with 95% confidence interval. The difference of disease prevalence between various leprosy groups was compared using an unpaired t test. The association between eye symptoms and potentially sight-threatening complications was analyzed using the chi-square test., Results: Three hundred eighty-six of the 446 patients with multibacillary HD residing in the defined areas were evaluated. Four patients (1.04%; 95% confidence interval [CI], 0.0%-2.0%) were bilaterally blind; 33 (8.55%; 95% CI, 5.8%-11.3%) had unilateral blindness. Mean intraocular pressure was 12 mmHg (standard deviation, 4.1 mmHg), and prevalence of glaucoma was 3.6% (95% CI, 1.8%-5.5%). Potentially sight-threatening (PST) pathologic features (corneal anesthesia, lagophthalmos, uveitis, scleritis, and advanced glaucoma) were present in 10.4% (95% CI, 7.4%-13.4%) of patients. Significant cataracts occurred 3 times more frequently in those with polar lepromatous leprosy. The odds ratio for PST pathology in the presence of patient-reported symptoms (pain, redness, inability to close eye, burning, and irritation) was 2.9 (95% CI, 1.34-6.26)., Conclusions: Patients who have completed treatment for multibacillary HD continue to have significant ocular morbidity. A history of specific eye symptoms can be the basis for referral by field staff.

Background: Several studies have shown the efficacy, tolerability, and ease of administration of pemetrexed-an antifolate antineoplastic agent-in patients with advanced non-small-cell lung cancer. We assessed pemetrexed as maintenance therapy in patients with this disease., Methods: This randomised double-blind study was undertaken in 83 centres in 20 countries. 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy were randomly assigned (2:1 ratio) to receive pemetrexed (500 mg/m(2), day 1) plus best supportive care (n=441) or placebo plus best supportive care (n=222) in 21-day cycles until disease progression. Treatment was randomised with the Simon and Pocock minimisation method. Patients and investigators were masked to treatment. All patients received vitamin B(12), folic acid, and dexamethasone. The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00102804., Findings: All randomly assigned participants were analysed. Pemetrexed significantly improved progression-free survival (4.3 months [95% CI 4.1-4.7] vs 2.6 months [1.7-2.8]; hazard ratio [HR] 0.50, 95% CI 0.42-0.61, p<0.0001) and overall survival (13.4 months [11.9-15.9] vs 10.6 months [8.7-12.0]; HR 0.79, 0.65-0.95, p=0.012) compared with placebo. Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group (21 [5%] vs three [1%]). Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo (70 [16%] vs nine [4%]; p<0.0001), specifically fatigue (22 [5%] vs one [1%], p=0.001) and neutropenia (13 [3%] vs 0, p=0.006). No pemetrexed-related deaths occurred. Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy (227 [51%] vs 149 [67%]; p=0.0001)., Interpretation: Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer., Funding: Eli Lilly.

Endoscopic ultrasound (EUS) has become well established as a diagnostic modality in gastrointestinal cancer staging. It offers high-resolution imaging and fine-needle biopsy, which is essential in tumor and nodal staging of gastrointestinal cancers. In the recent decade, however, many therapeutic applications of EUS have become possible. Currently, interventional EUS endoscopy involves celiac plexus neurolysis, pseudocyst drainage, and intratumoral fine-needle injection therapy for inoperable pancreatic malignancy. Emerging techniques include the accurate endoscopic delivery of radioactive beads to localize tumor therapy as well as other therapies, such as radiofrequency ablation or cryotherapy. Diagnostic and therapeutic access to the biliary tree and pancreatic duct is increasingly being used successfully in failed endoscopic retrograde cholangiopancreatography (ERCP) procedures. This review discusses these procedures and several evolving future applications, including vascular access and EUS-guided enteral anastomosis.

Vascular smooth muscle cell (VSMC) migration and proliferation are critical events in the development of neointima following vascular injury. In this study, we found that CD9 is constitutively expressed in the VSMC of the neointima of injured carotid arteries. The in vitro migration and proliferation of human coronary artery smooth muscle (hCASM) cells were reduced by 40% and 63%, respectively, by treatment with a CD9 specific monoclonal antibody mAb7 when compared to control antibody treatment. In a mouse carotid ligation injury model, a single application of a neutralizing anti-mouse CD9 antibody resulted in a 31% (day 14, n=8, p<0.05), and 32% (day 28, n=5, p<0.01) reduction in neointima formation. In support of these findings, exogenous expression of human CD9 by CD9-adenoviral transduction led to 43% increases in neointima (p<0.05, n=6). Upon investigation of the mechanisms underlying CD9 mediated VSMC phenotypic events we found that integrin alpha5beta1 was a constitutive partner of CD9 and that CD9 significantly augmented PI-3 kinase dependent Akt phosphorylation. Furthermore, enhanced Akt phosphorylation was attenuated by mAb7 binding. Cumulatively, a functional link between CD9, alpha5beta1, PI3-K/Akt activity and enhanced VSMC migratory and proliferative phenotypes has been demonstrated. These studies suggest that agents that modulate CD9 mediated VSMC phenotypes may emerge as novel strategies for the treatment of abnormal vascular injury response.

Little is known about the behavior of the ovarian surface epithelium (OSE), which plays a central role in ovarian cancer etiology. It has been suggested that incessant ovulation causes OSE changes leading to transformation and that high gonadotropin levels during postmenopause activate OSE receptors, inducing proliferation. We examined the chronology of OSE changes, including tumor appearance, in a mouse model where ovulation never occurs due to deletion of follitropin receptor. Changes in epithelial cells were marked by pan-cytokeratin (CK) staining. Histologic changes and CK staining in the OSE increased from postnatal day 2. CK staining was observed inside the ovary by 24 days and increased thereafter in tumor-bearing animals. Ovaries from a third of aged (1 year) mutant mice showed CK deep inside, indicating cell migration. These tumors resembled serous papillary adenoma of human ovaries. Weak expression of GATA-4 and elevation of PCNA, cyclooxygenase-1, cyclooxygenase-2, and platelet-derived growth factor receptors alpha and beta in mutants indicated differences in cell proliferation, differentiation, and inflammation. Thus, we report that OSE changes occur long before epithelial tumors appear in FORKO mice. Our results suggest that neither incessant ovulation nor follicle-stimulating hormone receptor presence in the OSE is required for inducing ovarian tumors; thus, other mechanisms must contribute to ovarian tumorigenesis.

Ovarian cancer is a deadly disease with long latency. To understand the consequences of loss of follicle-stimulating hormone receptor (FSH-R) signaling and to explore why the atrophic and anovulatory ovaries of follitropin receptor knockout (FORKO) mice develop different types of ovarian tumors, including serous papillary epithelial adenoma later in life, we used mRNA expression profiling to gain a comprehensive view of misregulated genes. Using real-time quantitative reverse transcription-polymerase chain reaction, protein analysis, and cellular localization, we show, for the first time, in vivo evidence that, in the absence of FSH-R signaling, claudin-3, claudin-4, and claudin-11 are selectively upregulated, whereas claudin-1 decreases in ovarian surface epithelium and tumors in comparison to wild type. In vitro experiments using a mouse ovarian surface epithelial cell line derived from wild-type females reveal direct hormonal influence on claudin proteins. Although recent studies suggest that cell junction proteins are differentially expressed in ovarian tumors in women, the etiology of such changes remains unclear. Our results suggest an altered hormonal environment resulting from FSH-R loss as a cause of early changes in tight junction proteins that predispose the ovary to late-onset tumors that occur with aging. More importantly, this study identifies claudin-11 overexpression in mouse ovarian serous cystadenoma.

The management of solid organ cancers relies on accurate staging. Once distal metastasis has been excluded by conventional radiographic methods, local staging of the tumor and its nodal involvement is essential to determine the most optimal therapeutic approach. Many radiographic imaging modalities are unable to determine subtle tumor involvement. However, the emergence of endoscopic ultrasonography (EUS) has given promise to improved staging with its unique ability to examine tumors from within the gastrointestinal lumen with extremely close proximity. An additional advantage is the ability to perform fine-needle aspiration (FNA) biopsy to confirm or exclude tumor involvement. Many studies have shown superior accuracy in staging with EUS and EUS-FNA for tumors of the esophagus, stomach, pancreas, rectum, and mediastinum, including lung cancer. This review illustrates the principles of EUS and its role in staging of a variety of cancers and particularly its role alongside other imaging modalities.

Chronic mesenteric ischemia is an unusual but important cause of abdominal pain. Although this condition accounts for only 5% of all intestinal ischemic events, it can have significant clinical consequences. Among its many causes, atherosclerotic occlusion or severe stenosis is the most common. This disorder has an indolent course that results in extensive collateral vascular formation. Thus, symptoms occur when at least two of the three main splanchnic vessels are affected. Intestinal angina, weight loss, and sitophobia are common clinical features. Diagnosis can often be made by noninvasive methods such as computerised axial tomographic angiography, magnetic resonance angiography, and duplex ultrasonography as well as by invasive catheter angiography. Therapy of chronic mesenteric ischemia depends on the extent and location of vascular disease. Alternatives to traditional surgical bypass are becoming more common including embolectomy, thrombolysis, and percutaneous angioplasty with vascular stenting. Early intervention is vital as the natural course of this illness can be debilitating. Furthermore, this has potential to develop into life-threatening acute mesenteric ischemia with subsequent bowel infarction and death. Long-term studies have shown that the risk of developing symptoms from asymptomatic but significant mesenteric vascular disease is 86% with overall 40% mortality rate. The recognition and management of this unusual but important cause of abdominal pain is discussed in detail in this review.

Different rates of suicide have been reported in India. In Vellore, southern India, we have noted that the rates of suicides are several fold higher than those reported anywhere in the world, especially in young women. The department of community health at the Christian Medical College, Vellore, has obtained data prospectively on births, deaths, and morbidity in a population of 108?000. We used the verbal autopsy method to assign cause of death. The mortality rates were analysed for 10 years, from 1992 to 2001, for the age-group 10-19 years. Suicides accounted for about a quarter of all deaths in young men and between 50% and 75% of all deaths in young women. The average suicide rate for young women was 148 per 100?000, and for young men 58 per 100?000. We believe that our findings are reliable. The system of surveillance is well established and the verbal autopsy method has been validated. These very high rates of suicide need urgent intervention.