Parametric optimization of hexavalent chromium removal by electrocoagulation technology with vertical rotating cylindrical aluminum electrodes using Taguchi and ANN model.

This study aims to evaluate the performance of rotating aluminum electrodes in the electrocoagulation reactor for removing hexavalent chromium (Cr6+) from synthetic tannery wastewater. Taguchi and Artificial Neural Network (ANN) based models were developed to obtain the optimum condition for maximum Cr6+ removal. The optimum working condition obtained by Taguchi approach for the maximum Cr6+ removal (94%) was: Initial Cr6+ concentration (Cr6+ i) = 15 mg/L; Current Density (CD) = 14.25 mA/cm2; Intial pH = 5; Rotational Speed of Electrode (RSE) = 70 rpm. In contrast, the optimal condition for maximum Cr6+ ions removal (98.83%) obtained from the BR-ANN model was: Cr6+ i = 15 mg/L; CD = 14.36 mA/cm2; pHi = 5.2; RSE = 73 rpm. Compared to the Taguchi model, the BR-ANN model outperformed in terms of providing higher Cr6+ removal (+ 4.83%); reduced energy demand (-0.035 KWh/gm Cr6+ remove); lower error function value (χ2 = -7.9674 and RMSE = -3.5414); and highest R2 value (0.9991). The data for the conditions 91,007 < Re < 227,517 and Sc = 102.834 were found to fit the equation for the initial Cr6+ concentration of 15 mg/l; Sh = 3.143Re0.125 Sc0.33. The Cr6+ removal kinetics was best described by Pseudo 2nd Order model, as validated by high R2 and lower error functions value. The SEM and XRF analysis confirmed that Cr6+ was adsorbed and precipitated along with metal hydroxide sludge. The rotating electrode led to lower SEEC (10.25 kWh/m3), as well as maximum Cr6+ removal (98.83%), compared to EC process with stationary electrodes.

Organochlorine pesticides induce epithelial as well as inflammatory mediators following exposure to human ovarian surface epithelial cells: An in vitro study.

Although studies have suggested organochlorine pesticides (OCPs) exposure increased the risk of epithelial ovarian cancer, the mechanisms underlying its potential tumorigenic effects in the human ovary are not well understood. In this study, we investigated the impact of dichlorodiphenyldichloroethylene (DDE), endosulfan, and heptachlor exposure on epithelial cadherin (E-cadherin) and proinflammatory mediators in human ovary surface epithelial (HOSE) cells. We found that DDE, endosulfan, and heptachlor exposure resulted in epithelial differentiation accompanied by upregulation of E-cadherin expression and overexpression of proinflammatory cytokines (TNFα, IL-1ß, and IL-6) in HOSE cells. The epithelial differentiation may accelerate HOSE cells to inclusion body formation, a common site for ovarian cancer initiation and persistent exposure to OCPs creates a chronic inflammatory microenvironment that may promote the neoplastic transformation of HOSE cells within the inclusion cyst.

Adverse childhood experiences and substance misuse in young people in India: results from the multisite cVEDA cohort.

BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).

Expression Analysis of MicroRNA-21 and MicroRNA-122 in Hepatocellular Carcinoma.

BACKGROUND/OBJECTIVE: Hepatocellular carcinoma (HCC) is a multistep process starting from chronic hepatitis (CH) that progress through cirrhosis to HCC. The expression level of microRNA (miRNA) was found to be deregulated in HCC. The study was designed to find out whether the expression level of miR-21 and miR-122 was deregulated in HCC compared to controls without HCC. METHODS: Real-time quantitative polymerase chain reaction was performed to find out the miRNA expression level using Ct value followed by statistical analysis where P value ≤ 0.05 was considered as significant. RESULTS: Overexpression of miR-21 and miR-122 in HCC was detected. All changes in the expression level of miR-21 and miR-122 were due to HCC compared with healthy control, CH, and liver cirrhosis. Hence miR-21 and miR-122 are suitable to differentiate HCC with an efficient diagnostic power of sensitivity, specificity, and expression level, but they might not have any role in patients' survival. CONCLUSION: miR-21 and miR-122 could be considered as potential markers of HCC screening molecule in addition to other approved markers. However the current study is limited to expression levels of miRNAs from serum; therefore, it needs further validated study in a large group of population to fulfill all the criteria of a biomarker.

Cadmium level in brain correlates with memory impairment in F1 and F2 generation mice: improvement with quercetin.

The increased exposure to cadmium (Cd) through environmental pollutants, food and cigarette smoke is a concern worldwide. The association of Cd with impaired learning disabilities led us to hypothesise that cadmium levels in brain tissue could be dose-dependently related to the extent of memory impairment and oxidative stress. In this study, we proposed to study whether cadmium exposure to dams could alter the brain Cd levels, memory parameters, antioxidant enzymes in brain and their gene expression in the F1-F2 generation mice and whether quercetin could modulate this effect. Animals were administered Cd alone and in combination with quercetin for 7 days during their gestation period. Their newborn pups (F1 and F2 mice) were reared until adulthood and were tested for memory using Morris water maze and step-down latency test. The brain tissue of F1 mice was collected. Cd levels were estimated using the atomic absorption spectrophotometer. G-S-transferase (GST) and catalase (CAT) activity were measured and fold increase in their respective gene expression was observed using the RT-PCR method. Cd levels were significantly increased in the brain tissue of animals exposed to Cd but cotreatment with quercetin showed decreased levels in both generations. Memory impairment was observed in animals of F1 generation exposed to Cd and cotreatment with quercetin (100 mg/kg) reversed this effect. Cd exposure significantly enhanced both activity and expression of GST and CAT in the brain tissue of F1 generation mice and quercetin attenuated this effect. In F2 generation, results were variable. GST activity and expression increased with Cd and decreased with quercetin cotreatment. However, CAT activity showed no significant change despite a decrease in gene expression. Quercetin cotreatment enhanced activity as well gene expression in F2 generation. Our study insinuates that Cd levels could act as a predictor of memory impairment and altered enzyme activity and gene expression in brain tissue. Quercetin helped to reduce Cd levels in brain tissue of F1 and F2 generation and modulated the antioxidant system of the cell by affecting expression of antioxidant enzymes at the transcription level.

Roadside Exposure and Inflammation Biomarkers among a Cohort of Traffic Police in Kathmandu, Nepal.

Air pollution is a major environmental problem in the Kathmandu Valley. Specifically, roadside and traffic-related air pollution exposure levels were found at very high levels exceeding Nepal air quality standards for daily PM2.5. In an exposure study involving traffic police officers, we collected 78 blood samples in a highly polluted spring season (16 February 2014⁻4 April 2014) and 63 blood samples in the less polluted summer season (20 July 2014⁻22 August 2014). Fourteen biomarkers, i.e., C-reactive protein (CRP), serum amyloid A (SAA), intracellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), interferon gamma (IFN-γ), interleukins (IL1-ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13), and tumor necrosis factor (TNF-α) were analyzed in collected blood samples using proinflammatory panel 1 kits and vascular injury panel 2 kits. All the inflammatory biomarker levels were higher in the summer season than in the spring season, while particulate levels were higher in the spring season than in the summer season. We did not find significant association between 24-hour average PM2.5 or black carbon (BC) exposure levels with most of analyzed biomarkers for the traffic volunteers working and residing near busy roads in Kathmandu, Nepal, during 2014. Inflammation and vascular injury marker concentrations were generally higher in females, suggesting the important role of gender in inflammation biomarkers. Because of the small sample size of female subjects, further investigation with a larger sample size is required to confirm the role of gender in inflammation biomarkers.

Clinical and laboratory profile of anti-M.

Anti-M is a frequently detected naturally occurring antibody that has been reported in various clinical settings and also in voluntary donors. We describe here the clinical and laboratory findings of 11 cases with anti-M detected at our center. This report is a retrospective study in which we reviewed our immunohematology laboratory records for cases involving anti-M. Both donor and patient data from a 28-month period (September 2014 to December 2016) were reviewed. During this period, 11 examples of anti-M were detected (8 patients, 1 voluntary whole blood donor, and 1 hematopoietic stem cell donor. Anti-M was also detected in one external quality assessment scheme sample received during this period. In conclusion, anti-M can be detected in various clinical settings. This antibody can be clinically significant; in the laboratory, it can present as a serologic problem such as an ABO group discrepancy or an incompatible crossmatch. After detection, management and course of action is determined by both the antibody characteristics and the clinical setting.Anti-M is a frequently detected naturally occurring antibody that has been reported in various clinical settings and also in voluntary donors. We describe here the clinical and laboratory findings of 11 cases with anti-M detected at our center. This report is a retrospective study in which we reviewed our immunohematology laboratory records for cases involving anti-M. Both donor and patient data from a 28-month period (September 2014 to December 2016) were reviewed. During this period, 11 examples of anti-M were detected (8 patients, 1 voluntary whole blood donor, and 1 hematopoietic stem cell donor. Anti-M was also detected in one external quality assessment scheme sample received during this period. In conclusion, anti-M can be detected in various clinical settings. This antibody can be clinically significant; in the laboratory, it can present as a serologic problem such as an ABO group discrepancy or an incompatible crossmatch. After detection, management and course of action is determined by both the antibody characteristics and the clinical setting.

Serum and Urinary Hepcidin for Diagnosing Iron-deficiency Anemia in Under-5 Children.

Bone marrow iron estimation remains the gold standard for diagnosing iron-deficiency anemia (IDA); serum ferritin, total iron-binding capacity, and transferrin saturation are routinely used as surrogate markers of IDA. However, these tests are marred by problems like poor specificity and sensitivity. Recently, hepcidin, a protein hormone synthesized in the liver and excreted in urine, has been shown to be related to iron status. We estimated the serum and urinary hepcidin levels in healthy children 6 to 60 months of age with (n=30) and without IDA (n=30). The mean (SD) serum hepcidin levels in children with IDA were significantly lower than those in children without IDA (3.03 [1.06] vs. 4.78 [3.94] ng/mL; P=0.02). The mean (SD) urinary hepcidin levels were also significantly lower in children with IDA than those in children without IDA (2.29 [0.53] vs. 2.79 [0.75] ng/mL; P=0.004). Performance of urinary and serum hepcidin compared with serum ferritin (<12 µg/L) for diagnosing IDA in terms of area under the receiver operating characteristic curve was 0.704 (P=0.007) and 0.59 (P=0.22), respectively. Serum hepcidin is not useful for diagnosing IDA in under-5 children. In contrast, urinary hepcidin holds promise as a noninvasive diagnostic tool for IDA in under-5 children.

Delineating Potential Transcriptomic Association with Organochlorine Pesticides in the Etiology of Epithelial Ovarian Cancer.

BACKGROUND: Recent studies have shown that there is an increased risk of Epithelial Ovarian Cancer (EOC) with Organochlorine Pesticides (OCPs). However, the alteration in the gene expression profile has not been explored so far. The goal of the present study is to understand the probable molecular mechanism of OCPs toxicity towards discovery of dysregulation of signaling pathway associated with differential gene expression and candidate transcriptomic set of markers in the pathophysiology of EOC in OCPs exposed population. METHODS: The OCP levels were estimated by gas chromatography and whole genome differential expression study was carried out using expression microarray and candidate genes were validated using Real time RT-PCR. RESULTS: Significant level of OCP residues such as ß-hexachlorocyclohexane (ß-HCH), Heptachlor, Heptachlor epoxide B (HTEB), dichlorodiphenyldichloroethylene (p'p'-DDE) and endosulfan-I was found between healthy and EOC patients. The transcriptome profile of several genes revealed regulation of various important cellular processes such as metabolism, inflammation, cytoskeleton dysregulation of TGF and WNT pathway in EOC cases with high OCPs. CONCLUSION: This study provides the first evidence showing that differentially expressed genes and dysregulation of signaling pathways might be associated with significant level of OCPs exposure in ovary tissue of epithelial ovarian cancer patients. Moreover, significant correlation of these genes with OCPs revealed that OCPs exposure played vital role in dysregulation of related pathways in the etiology of EOC.

Lead-induced DNA damage and cell apoptosis in human renal proximal tubular epithelial cell: Attenuation via N-acetyl cysteine and tannic acid.

This study investigates the exposure of lead-induced reactive oxygen species (ROS) generation, DNA damage, and apoptosis and also evaluates the therapeutic intervention using antioxidants in human renal proximal tubular cells (HK-2 cells). Following treatment of HK-2 cells with an increasing concentration of lead nitrate (0-50 µM) for 24 h, the intracellular ROS level increased whereas the GSH level decreased significantly in a dose-dependent manner. Comet assay results revealed that lead nitrate showed the ability to increase the levels of DNA strand breaks in HK-2 cells. Lead exposure also induced apoptosis through caspase-3 activation at 30 µg/mL. Pretreatment with N-acetylcysteine (NAC) and tannic acid showed a significant ameliorating effect on lead-induced ROS, DNA damage, and apoptosis. In conclusion, lead induces ROS, which may exacerbate the DNA damage and apoptosis via caspase-3 activation. Additionally, supplementation of antioxidants such as NAC and tannic acid may be used as salvage therapy for lead-induced DNA damage and apoptosis in an exposed person.

A prospective comparative clinical study of peripheral blood counts and indices in patients with primary brain tumors.

BACKGROUND: Elevation of the neutrophil to lymphocyte ratio (NLR) has been shown to be an indicator of poor prognosis in many malignancies including recurrent glioblastoma multiforme. OBJECTIVES: This study was aimed at assessing if the NLR and other leukocyte counts and indices were deranged in treatment-naïve patients with primary brain tumors when compared with an age-matched healthy control group. MATERIALS AND METHODS: This was a prospective comparative clinical observational study by design. A healthy control population was compared with treatment-naïve patients diagnosed with intra- and extraaxial brain tumors. Leukocyte counts (neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts) as well as leukocyte ratios such as the NLR and the monocyte to lymphocyte ratio (MLR) were calculated. We also evaluated if the counts and indices were related to the tumor volume. RESULTS: In all patients with tumors, the platelet and neutrophil counts were elevated when compared to the controls. In contrast, monocyte counts and the MLR were found to be decreased in patients with tumors when compared to the controls. The subset of patients with glioblastoma showed a significant increase in NLR when compared to the controls. CONCLUSIONS: Significant changes in the neutrophil, monocyte, and platelet counts as well as NLR and MLR were observed. Prospective longitudinal studies are required to determine the prognostic and therapeutic implications of these findings.

Cadmium exposure during lactation causes learning and memory-impairment in F1 generation mice: amelioration by quercetin.

Cadmium (Cd) is a known pollutant present in the environment at low levels and is reported to affect reproduction in many ways. The present study was undertaken to explore the effect of Cd in F1 generation mice on cognitive parameters, and to further investigate whether quercetin could modulate these effects. In this study, female lactating mice were exposed to cadmium for seven days just after delivery. The new born pups in their adulthood were tested for learning and memory parameters by passive avoidance task and Morris water maze (MWM) test. It was observed that pups exposed to Cd showed significant impairment of memory in step down latency test, which was reversed by quercetin (100 mg/kg). In MWM test for spatial memory, animals exposed to Cd exhibited increased escape latency, which was reversed by quercetin (50 mg/kg) significantly. Quercetin alone (50 and 100 mg/kg) also demonstrated improved spatial memory, and showed improved retention memory in the passive avoidance paradigm at dose 50 mg/kg. On testing oxidative stress parameters, we observed significantly increased malondialdehyde (MDA) levels in brain tissue of Cd-treated mice. Moreover, co-treatment with quercetin (50 mg/kg) and Cd significantly reduced these MDA levels. The other doses (25 and 100 mg/kg) also showed reduction in MDA levels as compared to the group exposed to Cd alone, though the difference was not statistically significant. Hence, this study highlights the possibility of cognitive impairment in adulthood if there is Cd exposure during lactation and oxidative stress could possibly attribute to this effect.

Effect of Low-Intensity Microwave Radiation on Monoamine Neurotransmitters and Their Key Regulating Enzymes in Rat Brain.

The increasing use of wireless communication devices has raised major concerns towards deleterious effects of microwave radiation on human health. The aim of the study was to demonstrate the effect of low-intensity microwave radiation on levels of monoamine neurotransmitters and gene expression of their key regulating enzymes in brain of Fischer rats. Animals were exposed to 900 MHz and 1800 MHz microwave radiation for 30 days (2 h/day, 5 days/week) with respective specific absorption rates as 5.953 × 10(-4) and 5.835 × 10(-4) W/kg. The levels of monoamine neurotransmitters viz. dopamine (DA), norepinephrine (NE), epinephrine (E) and serotonin (5-HT) were detected using LC-MS/MS in hippocampus of all experimental animals. In addition, mRNA expression of key regulating enzymes for these neurotransmitters viz. tyrosine hydroxylase (TH) (for DA, NE and E) and tryptophan hydroxylase (TPH1 and TPH2) (for serotonin) was also estimated. Results showed significant reduction in levels of DA, NE, E and 5-HT in hippocampus of microwave-exposed animals in comparison with sham-exposed (control) animals. In addition, significant downregulation in mRNA expression of TH, TPH1 and TPH2 was also observed in microwave-exposed animals (p < 0.05). In conclusion, the results indicate that low-intensity microwave radiation may cause learning and memory disturbances by altering levels of brain monoamine neurotransmitters at mRNA and protein levels.

Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities.

Notch activity regulates tumor biology in a context-dependent and complex manner. Notch may act as an oncogene or a tumor-suppressor gene even within the same tumor type. Recently, Notch signaling has been implicated in cellular senescence. Yet, it remains unclear as to how cellular senescence checkpoint functions may interact with Notch-mediated oncogenic and tumor-suppressor activities. Herein, we used genetically engineered human esophageal keratinocytes and esophageal squamous cell carcinoma cells to delineate the functional consequences of Notch activation and inhibition along with pharmacological intervention and RNA interference experiments. When expressed in a tetracycline-inducible manner, the ectopically expressed activated form of Notch1 (ICN1) displayed oncogene-like characteristics inducing cellular senescence corroborated by the induction of G0/G1 cell-cycle arrest, Rb dephosphorylation, flat and enlarged cell morphology and senescence-associated ß-galactosidase activity. Notch-induced senescence involves canonical CSL/RBPJ-dependent transcriptional activity and the p16(INK4A)-Rb pathway. Loss of p16(INK4A) or the presence of human papilloma virus (HPV) E6/E7 oncogene products not only prevented ICN1 from inducing senescence but permitted ICN1 to facilitate anchorage-independent colony formation and xenograft tumor growth with increased cell proliferation and reduced squamous-cell differentiation. Moreover, Notch1 appears to mediate replicative senescence as well as transforming growth factor-ß-induced cellular senescence in non-transformed cells and that HPV E6/E7 targets Notch1 for inactivation to prevent senescence, revealing a tumor-suppressor attribute of endogenous Notch1. In aggregate, cellular senescence checkpoint functions may influence dichotomous Notch activities in the neoplastic context.

A rare case of adult acute lymphoblastic leukemia presenting with paraparesis and multiple osteolytic lesions.

Acute lymphoblastic leukemia presenting with bone involvement and multiple osteolytic lesions has been commonly reported in pediatric population. Various myeloid and lymphoid malignancies can rarely present with bony lesions. We are reporting an adult female patient with acute lymphoblastic leukemia who presented with paraparesis and multiple osteolytic lesions in skull initially giving false impression of multiple myeloma.