Modeling the effect of area deprivation on COVID-19 incidences: a study of Chennai megacity, India.

OBJECTIVES: Socio-economic inequalities may affect coronavirus disease 2019 (COVID-19) incidence. The goal of the research was to explore the association between deprivation of socio-economic status (SES) and spatial patterns of COVID-19 incidence in Chennai megacity for unfolding the disease epidemiology. STUDY DESIGN: This is an ecological (or contextual) study for electoral wards (subcities) of Chennai megacity. METHODS: Using data of confirmed COVID-19 cases from May 15, 2020, to May 21, 2020, for 155 electoral wards obtained from the official website of the Chennai Municipal Corporation, we examined the incidence of COVID-19 using two count regression models, namely, Poisson regression (PR) and negative binomial regression (NBR). As explanatory factors, we considered area deprivation that represented the deprivation of SES. An index of multiple deprivations (IMD) was developed to measure the area deprivation using an advanced local statistic, geographically weighted principal component analysis. Based on the availability of appropriately scaled data, five domains (i.e., poor housing condition, low asset possession, poor availability of WaSH services, lack of household amenities and services, and gender disparity) were selected as components of the IMD in this study. RESULTS: The hot spot analysis revealed that area deprivation was significantly associated with higher incidences of COVID-19 in Chennai megacity. The high variations (adjusted R2: 72.2%) with the lower Bayesian Information Criteria (BIC) (124.34) and Akaike's Information Criteria (AIC) (112.12) for NBR compared with PR suggests that the NBR model better explains the relationship between area deprivation and COVID-19 incidences in Chennai megacity. NBR with two-sided tests and P <0.05 were considered statistically significant. The outcome of the PR and NBR models suggests that when all other variables were constant, according to NBR, the relative risk (RR) of COVID-19 incidences was 2.19 for the wards with high housing deprivation or, in other words, the wards with high housing deprivation having 119% higher probability (RR = e0.786 = 2.19, 95% confidence interval [CI] = 1.98 to 2.40), compared with areas with low deprivation. Similarly, in the wards with poor availability of WaSH services, chances of having COVID-19 incidence was 90% higher than in the wards with good WaSH services (RR = e0.642 = 1.90, 95% CI = 1.79 to 2.00). Spatial risks of COVID-19 were predominantly concentrated in the wards with higher levels of area deprivation, which were mostly located in the northeastern parts of Chennai megacity. CONCLUSIONS: We formulated an area-based IMD, which was substantially related to COVID-19 incidences in Chennai megacity. This study highlights that the risks of COVID-19 tend to be higher in areas with low SES and that the northeastern part of Chennai megacity is predominantly high-risk areas. Our results can guide measures of COVID-19 control and prevention by considering spatial risks and area deprivation.

A mitogen-activated protein kinase kinase inhibitor induced compound skin toxicity with oedema in metastatic malignant melanoma.

We report three cases of skin toxicity associated with oral mitogen-activated protein kinase kinase (MEK) inhibitor treatment for metastatic malignant melanoma (MM). All three patients developed oedema, and a single patient experienced eyelash trichomegaly. This is the first known report of eyelash trichomegaly secondary to MEK inhibitor use. We also discuss possible mechanisms for MEK inhibitor-associated oedema development. This series supports the role of the dermatologist in the screening and management of patients in the rapidly developing oncology setting, as new targeted agents can give rise to marked skin toxicity.

Multi-Institutional Clinical Outcomes of Biopsy Gleason Grade Group 5 Prostate Cancers Treated With Contemporary High-Dose Radiation and Long-Term Androgen Deprivation Therapy.

AIMS: This multicentric retrospective study reports long-term clinical outcomes of non-metastatic grade group 5 prostate cancers treated with external beam radiotherapy (EBRT) alone with long-term androgen deprivation therapy (ADT). MATERIALS AND METHODS: Patients treated across 19 institutions were studied. The key endpoints that were evaluated were 5-year biochemical recurrence-free survival (bRFS), metastases-free survival (MFS), overall survival, together with EBRT-related acute and late toxicities. The impact of various prognostic factors on the studied endpoints was analysed using univariate and multivariate analyses. RESULTS: Among the 462 patients, 88% (405) had Gleason 9 disease and 31% (142) had primary Gleason pattern 5. A prostate-specific membrane antigen positron emission tomography-computed tomography scan was used for staging in 33% (153), 80% (371) were staged as T3/T4 and 30% (142) with pelvic nodal disease. The median ADT duration was 24 months; 66% received hypofractionated EBRT and 71.4% (330) received pelvic nodal irradiation. With a median follow-up of 56 months, the 5-year bRFS, MFS and overall survival were 73.1%, 77.4% and 90.5%, respectively. Primary Gleason pattern 5 was associated with worse bRFS, MFS and overall survival with hazard ratios of 0.51 (95% confidence interval 0.35 to 0.73, P < 0.001), 0.64 (95% confidence interval 0.43 to 0.96, P = 0.031) and 0.52 (95% confidence interval 0.28 to 0.97, P = 0.040), respectively, whereas pelvic nodal disease was associated with worse bRFS (hazard ratio 0.67, 95% confidence interval 0.46 to 0.98, P = 0.039) and MFS (hazard ratio 0.56, 95% confidence interval 0.37 to 0.85, P = 0.006). The acute and late radiation-related toxicities were low overall and pelvic nodal irradiation was associated with higher toxicities. CONCLUSION: Contemporary EBRT and long-term ADT led to excellent 5-year clinical outcomes and low rates of toxicity in this cohort of non-metastatic grade group 5 prostate cancers. Primary Gleason pattern 5 and pelvic node disease portends inferior clinical outcomes.

Association of polymorphisms in 9p21 region with CAD in North Indian population: replication of SNPs identified through GWAS.

Coronary artery disease (CAD) is one of the leading causes of death worldwide that is influenced by both environmental as well as genetic factors. Several recent genome-wide association studies (GWAS) have reported the association of multiple single nucleotide polymorphisms (SNPs) mainly in the 9p21 region with CAD. However, the association of these SNPs with CAD has not been rigorously tested in Indian population, which accounts for the largest incidences of CAD in the world. Herein, we genotyped six such SNPs (rs10116277, rs10757274, rs1333040, rs2383206, rs2383207 and rs1994016) identified through GWAS, in 754 individuals (311 angiography-confirmed CAD patients and 443 treadmill test controls) recruited mainly from North India to evaluate if these SNPs were associated with CAD. The minor allele frequency of these six SNPs was comparable to that reported in the respective GWAS. We found that three of these SNPs (rs10116277, rs1333040 and rs2383206) present at the locus 9p21 were significantly associated with CAD even after controlling for the confounding factors such as age, sex, body mass index, homocysteine, hypertension, diabetes, smoking, diet, etc. In conclusion, the locus 9p21 found to be significantly associated with cardiovascular diseases in the Caucasian populations seems to be also important in North Indian population.

A natural flavonoid, apigenin isolated from Clerodendrum viscosum leaves, induces G2/M phase cell cycle arrest and apoptosis in MCF-7 cells through the regulation of p53 and caspase-cascade pathway.

BACKGROUND: With 9.6 million deaths in 2018, cancer remains the second leading cause of death worldwide. Breast cancer is the most deadly type of cancer among females, with 55.2% of crude incidence rate and 16.6% of crude mortality rate. PURPOSE: The present study was aimed to investigate the anti-breast cancer potential of natural dietary flavonoid, apigenin isolated from Clerodendrum viscosum leaves. METHODS: Apigenin was evaluated for in-depth anticancer activity in MCF-7 cells using cell viability assay, cell cycle analysis, Annexin-V-FLUOS staining, ROS induction, morphological analysis, and western blot analysis. RESULTS: Apigenin showed selective cytotoxicity on MCF-7 cells with an IC50-56.72 ± 2.35 µM, while negligible cytotoxicity was observed on WI-38 cells. Further, the flow cytometer-based analysis showed that apigenin halted MCF-7 cells in the G2/M phase arrest followed by dose-dependent apoptosis. Moreover, the FACS and confocal microscopy results confirmed the elevation of intracellular ROS and nuclear fragmentation in apigenin-treated MCF-7 cells. Western blots showed up-regulation of cell cycle regulatory proteins, increased p53 expression, Bax/Bcl-2 ratio, activation of caspases, and cleavage of PARP. Finally, apigenin treatment in the presence of Pifithrin-µ showed decreased apoptotic population and it was further confirmed through western blotting study. The results revealed the vital role of p53 in apigenin-induced apoptosis in MCF-7 cells. CONCLUSIONS: In the present findings, treatment of apigenin-induced intracellular ROS in MCF-7 cells followed by induction of G2/M phase cell cycle arrest and further apoptosis through the regulation of p53 and caspase-cascade signaling pathway.

Selenium and cabbage and colon carcinogenesis in mice.

The influence of dietary selenium and cabbage on the formation of colon tumors in female Swiss mice treated with 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8] was reported. Mice received a control diet (laboratory chow), the control diet plus selenium in the drinking water (1 mg/liter), or the control diet with added cabbage (12.8 g/100 g diet). They also received 8 weekly sc injections of DMH. The experiment was divided into two time periods: a) from 5 weeks before the first injection until 3 days after the last one (initiation period), and b) the subsequent 19.5 weeks until sacrifice of the mice (promotion period). Selenium had a strong protective effect when given during the initiation period; adenomas were reduced to a much greater extent than adenocarcinomas. The only effect of selenium supplementation in the promotion period was a small decrease in adenomas. Cabbage apparently had two opposing actions. It increased tumor incidence, particularly adenocarcinomas, if given in the initiation period, but it reduced adenoma formation considerably when given in the promotion period.

Protective effect of beta-carotene against colon tumors in mice.

The effect of dietary beta-carotene on colon carcinogenesis induced by 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8] was studied in female inbred Swiss Webster (ICR) mice. At age 10 weeks and continuing throughout the experiment, mice received diets consisting mainly of natural foods (laboratory chow) and containing 2 or 22 mg beta-carotene/kg. At age 15 weeks they received 7 weekly sc injections of DMH (total dose: 196 mg DMH X diHCI/kg body wt). When autopsied 31 weeks after the first DMH injection, the incidence (percent of mice with tumors) and multiplicity (number of tumors/tumor-bearing mouse) of colon tumors were reduced by half in the mice supplemented with beta-carotene. There was a much greater decrease in adenocarcinomas than in adenomas. Mice observed for 13 additional weeks revealed that the mortality rate, due largely or wholly to colon cancer, was only about half in supplemented mice. Mice sacrificed 12 weeks after the first dose of DMH (i.e., well before tumors appeared) showed mild colon mucosal hyperplasia. beta-Carotene supplementation, however, did not alter this, indicating that the protective effect against colon cancer may have occurred at a late stage of carcinogenesis.

Recent advances in mycotoxins detection.

Mycotoxins contamination in both food and feed is inevitable. Mycotoxin toxicity in foodstuff can occur at very low concentrations necessitating early availability of sensitive and reliable methods for their detection. The present research thrust is towards the development of a user friendly biosensor for mycotoxin detection at both academic and industrial levels to replace conventional expensive chromatographic and ELISA techniques. This review critically analyzes the recent research trend towards the construction of immunosensor, aptasensor, enzymatic sensors and others for mycotoxin detection with a reference to label and label free methods, synthesis of new materials including nano dimension, and transuding techniques. Technological aspects in the development of biosensors for mycotoxin detection, current challenges and future prospects are also included to provide a overview and suggestions for future research directions.

Role of Shc in the activation of Ras in response to epidermal growth factor and nerve growth factor.

Treatment of the rat pheochromocytoma cell line PC12 with nerve growth factor (NGF) or epidermal growth factor (EGF) is known to result in activation of Ras. In response to EGF treatment, complexes form between Sos, Grb2 and tyrosine phosphorylated Shc and/or EGF receptor. In response to NGF treatment, complexes form between Sos, Grb2 and tyrosine phosphorylated Shc. While Shc is also found bound to the activated NGF receptor, Trk, no complexes were detectable that contained both Trk and Grb2 or Sos. In streptolysin O permeabilised cells, a tyrosine phosphopeptide, EGFR-Y1068P, which binds to the SH2 domain of Grb2, totally blocks growth factor induced formation of complexes between Grb2 and Shc or EGF receptor, and also blocks activation of nucleotide exchange on Ras. At low concentrations, another tyrosine phosphopeptide, TRK-Y490P, which binds to the SH2 domain of Shc, blocks growth factor induced formation of complexes between Shc and the EGF receptor or Trk, but fails to block activation of nucleotide exchange on Ras. Higher concentrations of TRK-Y490P inhibit tyrosine phosphorylation of Shc and the formation of Shc complexes with Grb2: this results in strong inhibition of Ras activation by NGF and partial inhibition of Ras activation by EGF. These data demonstrate that the formation of a trimeric complex between tyrosine phosphorylated Shc, Grb2 and Sos is the key event in the activation of Ras in response to NGF. The binding of Sos to tyrosine phosphorylated receptor, via Grb2 may also contribute to Ras activation by EGF but not NGF, while stable complex formation between Shc and receptors is not necessary for Ras activation by either growth factor.

Factors predicting mortality in newborn ventilation.

OBJECTIVE: Prediction of mortality among newborns on mechanical ventilation is difficult. Our aim was to develop a scoring system for predicting mortality among such neonates. METHODS: This multi centre prospective study was performed to develop and validate a scoring system among two equal cohorts of ventilated newborns in India. Mechanical ventilator was used in pressure-limited time-cycled mode. Arterial blood gas, initial pulmonary pressures, septicemia screen along with other basic parameters were recorded in a pre-structured proforma. Blood samples were analyzed for malondialdehyde to determine the possible role and predictive validity of free radical injury. Multiple logistic regression analysis was done to find out independent predictors of mortality for the variables those were significantly associated with outcome after univariate analysis. RESULTS: On univariate analysis, birth-weight, oxygenation-index, septicaemia, malondialdehyde level, and inotropic support were significantly associated with mortality. However, after multiple regression analysis gestational-age, pH and FiO2 lost their significance as predictors. According to cut-off values of ROC-curve, a scoring system ranging from 0 to 20 and four mortality risk groups were developed. Area under ROC-curve was 0.94, compared to 0.90 for both APACHE-III and CRIB-scores; and 0.92 for PRISM-score. CONCLUSIONS: Birth-weight, oxygenation-index, malondialdehyde level, inotropic support, and septicemia are independent mortality predictors of neonatal ventilation. Increase in malondialdehyde level is associated with higher mortality rate, indicating possible role of free radical injury. Pediatr Pulmonol. 2015; 50:271-275. © 2014 Wiley Periodicals, Inc.

Serum vitamin A and retinol-binding protein in patients with insulin-dependent diabetes mellitus.

Serum concentrations of vitamins A and E and retinol-binding protein (RBP) were measured in 25 late adolescent and young adult patients with insulin-dependent diabetes mellitus. Their serum vitamin A levels were significantly lower than those of nondiabetic control subjects of comparable age. The serum concentrations of RBP were also significantly lower in the diabetic patients. The serum levels of vitamin A in the diabetic patients as well as in the control subjects showed a significant linear regression with serum concentrations of RBP. Unlike vitamin A, serum concentrations of vitamin E were not significantly different between the two groups of subjects. These findings suggest that the reduced serum vitamin A levels in the diabetic patients reflect reduced mobilization of vitamin A from the liver.

Dietary fibre and the mouse colon: its influence on luminal pH, reducing activity and bile acid binding.

Female, Swiss mice were fed semi-synthetic diets for 33 days. The diets were fibre-free (FF) or supplemented with corn bran (CB) 12%, wheat bran (WB) 12%, alfalfa (AL) 12%, pectin (P) 6%, cellulose (CL) 6%, or lignin (LG) 6%. Fibre caused little hyperplasia of the colon mucosa. The number of cells per crypt was increased 9-13% and the crypt column length by 14-19% in the CL, AL and LG groups. CB caused rather less hyperplasia, WB less again and P caused none. The colon mucosal DNA content was approximately 5-10% lower in mice given supplemental fibre. The pH of the contents of the distal colon was apparently unaffected by fibre. Measurement of a non-specific, non-enzymic reducing activity indicated that activity was doubled by AL and LG, lowered 41% by CB but little changed by WB, CL and P. The deoxycholate binding capacity of the colon contents was increased 3--4-fold by LG, whereas the other fibre sources were without appreciable effect. This high binding capacity by LG was also seen in the material used for diet preparation. Analyses of the contents of the caecum and of the remaining colon indicated that as food residue passes from the caecum to the remaining colon little change in binding capacity occurs.