A hybrid deep CNN model for brain tumor image multi-classification.

The current approach to diagnosing and classifying brain tumors relies on the histological evaluation of biopsy samples, which is invasive, time-consuming, and susceptible to manual errors. These limitations underscore the pressing need for a fully automated, deep-learning-based multi-classification system for brain malignancies. This article aims to leverage a deep convolutional neural network (CNN) to enhance early detection and presents three distinct CNN models designed for different types of classification tasks. The first CNN model achieves an impressive detection accuracy of 99.53% for brain tumors. The second CNN model, with an accuracy of 93.81%, proficiently categorizes brain tumors into five distinct types: normal, glioma, meningioma, pituitary, and metastatic. Furthermore, the third CNN model demonstrates an accuracy of 98.56% in accurately classifying brain tumors into their different grades. To ensure optimal performance, a grid search optimization approach is employed to automatically fine-tune all the relevant hyperparameters of the CNN models. The utilization of large, publicly accessible clinical datasets results in robust and reliable classification outcomes. This article conducts a comprehensive comparison of the proposed models against classical models, such as AlexNet, DenseNet121, ResNet-101, VGG-19, and GoogleNet, reaffirming the superiority of the deep CNN-based approach in advancing the field of brain tumor classification and early detection.

Assessment of Biotransformed Silica Nanoparticle on Blood Glucose Level in Human: An In Vitro Investigation.

Diabetes has affected nearly half a billion people worldwide. According to current guidelines, glycemic control is essential to mitigate diabetic complications. The antihyperglycemic effects of various chemically synthesized nanoparticles have been reported in animal models. However, their impact on humans has not been previously reported. This study was conducted to biosynthesize and assess the antihyperglycemic property of silica nanoparticles (SiO2-NPs) since they are non-toxic and biocompatible. SiO2-NPs biosynthesized using the endophytic fungus Fusarium oxysporum. In this collaborative study, 26 people, either hyperglycemic or euglycemic, diagnosed at the Endocrinology Outpatients, according to the American Diabetes Association, USA, were recruited. Silica nanoparticles were characterized and assessed for in vitro antihyperglycemic property using blood samples. Particle size distribution based on TEM images confirms that the average size of silica nanoparticle is 25 nm and is monodispersed in nature. The XRD pattern shows that only one broad peak at 2θ = 220 corresponds to the plane (101) of silica nanoparticles. UV Visible spectra show the λmax at 270 nm, peaks in FTIR at 1536 cm-1, 1640 cm-1, and 3420 cm-1 for the protein cap. The mean blood glucose was 120.2 mg/dL in the 'SiO2-NP untreated' group and decreased to 97.24 mg/dL in the 'SiO2-NP treated' group. A paired t-test (P-value < 0.0001) indicates a strong relationship between antihyperglycemia and silica NP. In our study, it has been observed that the biosynthesized silica nanoparticles using the endophytic fungus Fusarium oxysporum show antihyperglycemic property in vitro.

Has COVID-19 suppressed dengue transmission in Nepal?

Following the report of the first COVID-19 case in Nepal on 23 January 2020, three major waves were documented between 2020 and 2021. By the end of July 2022, 986 596 cases of confirmed COVID-19 and 11 967 deaths had been reported and 70.5% of the population had received at least two doses of a COVID-19 vaccine. Prior to the pandemic, a large dengue virus (DENV) epidemic affected 68 out of 77 districts, with 17 932 cases and six deaths recorded in 2019. In contrast, the country's Epidemiology and Disease Control Division reported 530 and 540 dengue cases in the pandemic period (2020 and 2021), respectively. Furthermore, Kathmandu reported just 63 dengue cases during 2020 and 2021, significantly lower than the 1463 cases reported in 2019. Serological assay showed 3.2% positivity rates for anti-dengue immunoglobulin M antibodies during the pandemic period, contrasting with 26.9-40% prior to it. Real-time polymerase chain reaction for DENV showed a 0.5% positive rate during the COVID-19 pandemic which is far lower than the 57.0% recorded in 2019. Continuing analyses of dengue incidence and further strengthening of surveillance and collaboration at the regional and international levels are required to fully understand whether the reduction in dengue incidence/transmission were caused by movement restrictions during the COVID-19 pandemic.

Effect of mobile phone signal radiation on epigenetic modulation in the hippocampus of Wistar rat.

Exponential increase in mobile phone uses, given rise to public concern regarding the alleged deleterious health hazards as a consequence of prolonged exposure. In 2018, the U.S. National toxicology program reported, two year toxicological studies for potential health hazards from exposure to cell phone radiations. Epigenetic modulations play a critical regulatory role in many cellular functions and pathological conditions. In this study, we assessed the dose-dependent and frequency-dependent epigenetic modulation (DNA and Histone methylation) in the hippocampus of Wistar rats. A Total of 96 male Wistar rats were segregated into 12 groups exposed to 900 MHz, 1800 MHz and 2450 MHz RF-MW at a specific absorption rate (SAR) of 5.84 × 10-4 W/kg, 5.94 × 10-4 W/kg and 6.4 × 10-4 W/kg respectively for 2 h per day for 1-month, 3-month and 6-month periods. At the end of the exposure duration, animals were sacrificed to collect the hippocampus. Global hippocampal DNA methylation and histone methylation were estimated by ELISA. However, DNA methylating enzymes, DNA methyltransferase1 (DNMT1) and histone methylating enzymes euchromatic histone methylthransferase1 (EHMT1) expression was evaluated by real-time PCR, as well as further validated with Western blot. Alteration in epigenetic modulation was observed in the hippocampus. Global DNA methylation was decreased and histone methylation was increased in the hippocampus. We observed that microwave exposure led to significant epigenetic modulations in the hippocampus with increasing frequency and duration of exposure. Microwave exposure with increasing frequency and exposure duration brings significant (p < 0.05) epigenetic modulations which alters gene expression in the hippocampus.

Modulation of mRNA Expression of IL-6 and mTORC1 and Efficacy and Feasibility of an Integrated Approach Encompassing Cognitive Behavioral Therapy Along with Pregabalin for Management of Neuropathic Pain in Postherpetic Neuralgia: A Pilot Study.

OBJECTIVE: This study was designed to explore the efficacy and feasibility of cognitive behavioral therapy (CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of messenger RNA (mRNA) expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients. DESIGN: Randomized controlled pilot study. METHODS: The patients aged >18 years of age with an established diagnosis of PHN with evident allodynia and hyperalgesia who had pain for at least 3 months after healing of rash with pain intensity ≥4/10 on NRS-Pain Scale were enrolled. The trial was registered with the Clinical Trials Registry-India (CTRI/2019/03/018014). A detailed baseline assessment regarding type and duration of pain and disability using pain-relevant self-report questionnaires was done. Two mL venous blood samples were collected for gene expression studies at base line and at end of 12 weeks of treatment. Patients were randomized into one of the two groups. Group PR received pregabalin and Group CP received CBT along with pregabalin. The pain intensity was measured using numeric rating scale (NRS)-Pain scale, neuropathic component of the pain by using Neuropathic Pain Symptom Inventory (NPSI) and Pain Detect Questionnaire (PDQ), sleep interference by NRS-Sleep, pain-related catastrophic thoughts by using Pain Catastrophizing Scale (PCS), depression and quality of life using Beck Depression Inventory-II (BDI-II) and Short Form-12 (SF-12), respectively. The research funding was supported by the intramural grant from the institution. RESULTS: A total of 40 patients with 20 in each group were included. Following integrated approach encompassing CBT and Pregabalin, group CP had significant downregulation of mRNA expression of IL-6; however, no such correlation was observed with mTOR expression. A significant decline in the intensity of pain, NPSI scoring for burning, allodynia, and pain-related catastrophizing were observed; also a significant improvement in depressive symptoms and quality of life were observed with the use of CBT. CONCLUSIONS: A significant downregulation of mRNA expression of IL-6 was observed; however, no significant correlation was observed between NRS pain score and ΔCt values of mRNA expression of both mTORC1 gene and IL-6 gene at baseline and at the end of 12th week. In addition, we note a significant decrease in pain intensity, depressive symptoms, and pain-related catastrophizing while improving QOL was observed with the use of CBT as a clinical adjunct along with pregabalin in PHN patients.

ß-Endosulfan-mediated induction of pro-fibrotic markers in renal (HK-2) cells in vitro: A new insight in the pathogenesis of chronic kidney disease of unknown etiology.

Chronic kidney disease of unknown etiology (CKDu), manifested clinically as tubulo interstitial fibrosis, has emerged as the second major cause of chronic kidney disease (CKD) in the Indian subcontinent and various agrochemicals have been implicated in its occurance. Among the agrochemicals organochlorine pesticides particularly endosulfan is well known for its toxicity and recent residue analysis have shown its presence in the blood samples of general population. In this present study, we have investigated the consequences of endosulfan exposure at a concentration (0.01 µM) equivalent to their highest reported presence in human blood sample of some CKDu patients, to human renal proximal tubular epithelial (HK-2) cell line with regard to ROS generation and expression of profibrotic and epithelial to mesenchymal (EMT) markers in order to find out endosulfan's ability to induce profibrotic changes in renal cell. We demonstrated a significant increase in intracellular ROS generation and increased expression of TGF-ß1 when cells were incubated with ß-endosulfan (0.01 µM) indicating occurrence of oxidative stress and fibrotic process. Again, decreased expression of epithelial marker E-cadherin and increase in the expression of mesenchymal marker α-smooth muscle actin (α-SMA) suggest possible onset of EMT process. Pre-treatment with 5 mM concentration of anti-oxidant N-acetyl cysteine partially attenuated the above process. In conclusion, these findings suggest possible involvement of ß-endosulfan in the development of CKDu through oxidative stress and profibrotic signaling.

Modulation of the Extracellular Signal-Regulated Protein Kinase and Tissue Inhibitors of Matrix Metalloproteases-1 Gene in Chronic Neuropathic Pain.

OBJECTIVES: The aim of this study is to study the modulation of extracellular signal-regulated protein kinase (ERK) and tissue inhibitors of matrix metalloproteases 1 (TIMP 1) gene in patients with neuropathic pain (NP). MATERIALS AND METHODS: In the present, cross-sectional, observational study, 2 ml of venous baseline sample was withdrawn from all the patients with neuropathic (NP) or non NP (NNP) soon after their diagnosis or on their first visit to the pain clinic. A real-time quantitative polymerase chain reaction experiment was conducted to measure the mRNA expression of TIMP1 and ERK genes in blood samples. The Delta Ct, Delta Ct, and fold change analysis of both the genes were conducted between patients with NP and NNP. RESULTS: A total of 285 patients with chronic pain were assessed, out of which, 153 patients had NP and 132 had NNP. The average duration of chronic pain was 11 months for 285 patients. The mRNA expression of TIMP1 gene is significantly down regulated (2.65-fold) (P (-f. 01), and the mRNA expression level of ERK is significantly up regulated (2.03-fold) (P (-f. 01) in NP patients when compared with NNP. CONCLUSION: The mRNA expression of TIMP1 gene is significantly down regulated, and ERK is significantly up regulated in patients with NP. Further, multicentric trials with larger sample size are recommended to confirm this finding.

Early lactate measurements for predicting in-hospital mortality in paediatric sepsis.

AIM: We compared the performance of plasma lactate with high-sensitivity C-reactive protein (hs-CRP), and paediatric sepsis-related organ failure assessment (pSOFA) score for predicting mortality in septic children. METHODS: Serial plasma lactate and hs-CRP levels and pSOFA score was assessed during early hospital stay in septic children. RESULTS: Out of 149 participants, 45 died. Plasma lactate at 0 h and 6 h was significantly higher, and lactate clearance was significantly lower in non-survivors. The optimal cut-off of plasma lactate at 6h for identifying mortality was 2.5 mmol/L (sensitivity 85% and specificity 74%). pSOFA score had the best predictive ability for mortality (AUC 0.89) followed by hs-CRP at 0 h (AUC 0.86), hs-CRP at 48 h (AUC 0.83), plasma lactate levels at 6 h (AUC 0.83), and plasma lactate at 0 h (AUC 0.67). CONCLUSION: pSOFA score, hs-CRP and hyperlactemia at 6 h can identify septic children at risk of dying.

Significance of MMP-9 and VEGF-C expression in North Indian women with breast cancer diagnosis.

Metastasis accounts for the majority of cancer-associated mortality and renders the targeted therapy fruitless in the patients of breast cancer. Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF-C) are thought to be involved in tumor progression and metastasis. The aim of this study was to investigate the expression of MMP-9 and VEGF-C at both mRNA and protein levels in breast cancer and to correlate with lymph node metastasis and other clinicopathological characteristics. Biopsy specimens (N = 100) of breast cancer & benign breast disease (N = 100) were investigated for the mRNA expression of MMP-9 and VEGF-C by Real-time PCR and Protein expression by Western blot. Elevated levels of MMP-9 (p < 0.001) and VEGF-C (p < 0.001) expression were detected in breast cancer with corresponding to benign breast disease. Additionally, we found significantly increased levels of MMP-9 and VEGF-C in node-positive group with respect to node-negative group. Moreover, the levels of MMP-9 were significantly increased in larger tumor size (T3/T4) (p < 0.05) as compared to smaller size (T1/T2), which suggests that MMP-9 plays an important role in the progression of breast cancer. VEGF-C expression was associated with the TNM stage of tumor (p < 0.05). Further, a significant positive correlation was established between the mRNA levels of these two genes (p < 0.001). However, we could not obtain any significant correlation between expression of these genes with other clinicopathological parameters like tumor grade, age, menopausal status, and receptor status like ER, PR, and Her2. This study suggests that the high expression of MMP-9 and VEGF-C could act as markers for the tumor presence in breast cancer. In addition, this study recommends that expression of MMP-9 and VEGF-C was significantly associated with lymph node status and may provide valuable diagnosis of lymph node metastasis in breast cancer patients. Further, MMP-9 expression was associated with the tumor size and VEGF-C expression was correlated with the staging of the tumor, although no association was observed with other clinicopathological variables.

Molecular evidence supports the expansion of visceral leishmaniasis towards non-program districts of Nepal.

BACKGROUND: Visceral Leishmaniasis (VL) is caused by a protozoan parasite Leishmania donovani that is transmitted to humans by an infected female sandfly, Phlebotomus argentipes. VL is common in the Indian sub-continent including Nepal and efforts for its elimination are ongoing. However, expansion of disease towards the higher altitude areas, previously considered as VL free in Nepal, may impact the ability to achieve the elimination target by 2020. METHODS: This was an exploratory study, where VL suspected patients living exclusively in the non-program districts of Nepal and presenting with fever > 2 weeks and splenomegaly was included. The patients' blood samples were collected, and DNA was extracted. DNA was subjected to PCR amplification and subsequent sequencing. Additionally, past 10 years data of VL cases from the national databases were analysed to see the trends of the disease in program and non program districts. RESULTS: Analysis of the past 10 years data revealed that trend of VL cases significantly decreased in the program districts (p = 0.001) while it increased in the non-program districts (p = 0.002). The national trend for overall incidence of VL also significantly decreased over this time period. Limited number of patients' samples (n = 14) were subjected to molecular investigation, and four patients were found to be positive for Leishmania species by PCR. Interestingly, these cases in non-program districts were indeed also L. donovoni complex. All four patients were male with age ranges from 10 to 68 years. GenBank BLAST of the obtained DNA sequences confirmed identified specimens as L. donovani complex. We identified additional VL cases from non-program districts (including the high lands) of Nepal, indicating that the infection could be an emerging threat for the non-program areas of Nepal. CONCLUSION: The demonstration of VL cases in areas initially considered non-endemic has raised concern about on-going transmission in those regions and may trigger subsequent government plan and action to include those areas in the elimination program. Thus, the government should consider revising the disease control programs to accommodate non-program districts for achieving the VL elimination goal set for 2020.

Genetic variations of IL-10: Identification of novel variations and evaluation of the impact of the SNPs/haplotype in the promoter region with the progression of Oral Squamous Cell Carcinoma in Indian population.

The correlation of interleukin 10 (IL-10) with the outbreak and progression of cancer has been well established as it contributes to tumor immune evasion. Convincing number of evidences has been accumulated to reflect the critical correlation between IL-10 polymorphism and tumorogenesis. Several polymorphic sites at promoter regions have been reported to be associated with cancer susceptibility. The purpose of this study was to examine the effect of modulated genotypes in the promoter region of IL-10 gene with life-style habits in oral squamous cell carcinoma (OSCC) in the Indian population. A total of 300 subjects (100 OSCC, 50 precancer and 150 healthy controls) were recruited in this study. The IL-10 promoter region was amplified in 14 overlapping fragments by PCR and further screened through the high throughput technique of denaturing high-performance liquid chromatography (dHPLC) followed by sequencing. We identified three novel variations at positions (-924, -1045 & -1066); we also found some known SNPs (-592C/A, -657G/A, -851G/A, -819C/T, -1082A/G). The identified novel variations were submitted to the NCBI Gene Bank (accession numbers KT153594, KT291742 and KT291743). We also noticed a significant association of polymorphisms (-592C/A, -819C/T and -1082A/G) individually as well as in combination (haplotypes) along with lifestyle habits for the risk of oral carcinoma (p<0.0001). We have reported three novel SNPs in the Indian population for the first time, and these SNPs may be associated with OSCC. Besides, we showed the first evidence of IL-10 haplotypes, i.e., CCG and CTG, may act as a biomarker for early detection of oral pre-cancerous/cancerous lesions or treatment management of oral carcinoma.

Expression analysis of apolipoproteins AI & AIV in hepatocellular carcinoma: A protein-based hepatocellular carcinoma-associated study.

Background & objectives: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. The objective of this study was to find out the differential expression of apolipoproteins (ApoAI and ApoAIV) in HCC and cases of liver cirrhosis and chronic hepatitis (controls) without HCC and to compare ApoAI and ApoAIV expression with alpha-foetoprotein (AFP), the conventional marker in HCC. Methods: Fifty patients with HCC and 50 controls comprising patients with liver cirrhosis (n=25) and chronic hepatitis (n=25) without HCC were included in this study. Total proteins were precipitated using acetone precipitation method followed by albumin and IgG depletion of precipitated protein using depletion kit. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expression changes of ApoAI and ApoAIV were confirmed by western blotting using specific primary and secondary polyclonal antibodies followed by densitometric protein semi-quantitative estimation. ApoAI, ApoAIV and AFP were measured in the plasma samples by ELISA method. Results: Semi-quantitative densitometric image analysis of the western blot images and the comparison between HCC patients with those without HCC (control) revealed differential expression of ApoAI and ApoAIV. Levels of ApoAI were significantly higher in patients with HCC compared to controls without HCC (0.279±0.216 vs 0.171±0.091 and 0.199±0.014; P <0.001). Levels of ApoAIV were significantly lower in patients of HCC compared to controls without HCC (0.119±0.061 vs 0.208±0.07 and 0.171±0.16; P <0.01). ELISA assays of apolipoproteins (ApoAI and ApoAIV) revealed similar results of expression of ApoAI and ApoAIV as detected in western blotting densitometric image analysis. Interpretation & conclusions: Increased expression of ApoAI and decreased expression of ApoAIV in HCC patients compared to controls without HCC revealed the abnormalities in HCC. These molecules need to be studied further for their use as potential biomarkers in the future diagnostic tools along with other conventional biomarkers for screening of HCC cases. It needs further analysis in higher number of patient population.

Assessing the feasibility of integration of self-care for filarial lymphoedema into existing community leprosy self-help groups in Nepal.

BACKGROUND: Lymphatic filariasis (LF) and leprosy are disabling infectious diseases endemic in Nepal. LF infection can lead to lymphoedema and hydrocoele, while secondary effects of leprosy infection include impairments to hands, eyes and feet. The disabling effects of both conditions can be managed through self-care and the supportive effects of self-help groups (SHGs). A network of SHGs exists for people affected by leprosy in four districts in Nepal's Central Development Region, however no such service exists for people affected by LF. The aim of this study was to determine the feasibility of integrating LF affected people into existing leprosy SHGs in this area. METHODS: A survey was conducted using a semi-structured questionnaire to elicit information on: (i) participant characteristics, clinical manifestation and disease burden; (ii) participants' knowledge of management of their condition and access to services; and (iii) participants' knowledge and perceptions of the alternate condition (LF affected participants' knowledge of leprosy and vice versa) and attitudes towards integration. RESULTS: A total of 52 LF affected and 53 leprosy affected participants were interviewed from 14 SHGs. On average, leprosy affected participants were shown to have 1.8 times greater knowledge of self-care techniques, and practiced 2.5 times more frequently than LF affected participants. Only a quarter of LF affected participants had accessed a health service for their condition, compared with 94.3% of leprosy affected people accessing a service (including SHGs), at least once a week. High levels of stigma were perceived by both groups towards the alternate condition, however, the majority of LF (79%) and leprosy (94.3%) affected participants stated that they would consider attending an integrated SHG. CONCLUSIONS: LF affected participants need to increase their knowledge of self-care and access to health services. Despite stigma being a potential barrier, attitudes towards integration were positive, suggesting that the SHGs may be a good platform for LF affected people to start self-care in this area. TRIAL REGISTRATION: This is not a registered trial.

Visceral leishmaniasis from a non-endemic Himalayan region of Nepal.

Visceral leishmaniasis (VL) is endemic to the southern plains of Nepal. Here, we report the first case of VL from a non-endemic Himalayan region of Nepal. The patient presented with a history of high-grade fever, splenomegaly, and anemia but had not traveled to a VL-endemic region. Visceral leishmaniasis was diagnosed following microscopic detection of the Leishmania species amastigote in a bone marrow aspirate, positive result for the rK39 test, and further validation by nested polymerase chain reaction (PCR). The patient was treated with 5 mg/kg liposomal amphotericin B and was clinically improved upon discharge. Our result suggests that VL is expanding towards non-endemic regions of Nepal, and it should therefore be considered that VL surveillance systems be strengthened, particularly for non-program districts and VL be included as a differential diagnosis in febrile illnesses.

Prevalence and genotypic diversity of Entamoeba species in inhabitants in Kathmandu, Nepal.

In Nepal, gastrointestinal infections due to parasites including Entamoeba species are common. The main aim of this study was to identify species of Entamoeba using genotypic analysis. The prevalence of Entamoeba infections was examined by PCR in fecal samples from 143 inhabitants living close to wild rhesus macaques in Kathmandu, Nepal. The numbers of positive cases were one (0.7%) for E. histolytica, eight (5.6%) for E. dispar, seven (4.9%) for E. coli, and two (1.4%) for E. chattoni (E. polecki ST2). No infections with E. nuttalli, E. moshkovskii, and E. polecki ST1 were found. In E. dispar, at least seven different genotypes were detected from the eight samples by sequence analysis of tRNA-linked short tandem repeats. Different genotypes were found even in a couple from the same family. This is the first report demonstrating that E. dispar with high genotypic diversity is prevalent, rather than E. histolytica, in Kathmandu, and that zoonotic transmission of E. chattoni from rhesus macaques might occur in the inhabitants.

Sero-epidemiology study of leptospirosis in febrile patients from Terai region of Nepal.

BACKGROUND: Leptospirosis is a re-emerging zoonotic disease caused by pathogenic strains of bacteria belonging to genus Leptospira whose symptoms can range from mild clinical manifestations to a severe life threatening illness. This disease may be under-recognized in resource poor settings like Nepal where many clinical laboratories lack appropriate equipment, technology and personnel for proper diagnosis. METHODS: We used IgM ELISA to estimate the sero-prevalence of leptospirosis in a group of febrile patients in a western region of Nepal. We also tested for possible co-infection with two other common febrile diseases endemic to Nepal including dengue and typhoid fever. RESULTS: Among samples from 144 febrile patients, 30 (21%) were positive for leptospiral IgM. In univariate analysis, leptospirosis was significantly associated with being of working age (p = 0.019), farming (p = 0.045) and water and animal contact (p = 0.0001). Widal and dengue serological study showed that the majority of leptospirosis infections did not have an alternative diagnosis. CONCLUSION: As indicated by the study, regular surveillance of animal reservoirs in collaboration with veterinary department and inclusion of leptospirosis as a differential diagnosis of febrile illness is thus recommended based on the current findings.

Organochlorine pesticide level in patients with chronic kidney disease of unknown etiology and its association with renal function.

BACKGROUND: Involvement of agrochemicals have been suggested in the development of chronic kidney disease of unknown etiology (CKDu). The association between CKDu and blood level of organochlorine pesticides (OCPs) in CKDu patients has been examined in the present study. METHODS: All the recruited study subjects (n = 300) were divided in three groups, namely, healthy control (n = 100), patients with chronic kidney disease of unknown etiology (n = 100), and patients with chronic kidney disease of known etiology (CKDk) (n = 100). Blood OCP levels of all three study groups were analyzed by gas chromatography. RESULTS: Increased level of OCPs, namely α-HCH, aldrin, and ß-endosulfan, were observed in CKDu patients as compared to healthy control and CKD patients of known etiology. The levels of these pesticides significantly correlated negatively with the estimated glomerular filtration rate (eGFR) and positively with urinary albumin of CKD patients. Logistic regression analysis revealed association of γ-HCH, p, p'-DDE, and ß-endosulfan with CKDu on adjustment of age, sex, BMI, and total lipid content. CONCLUSIONS: Increased blood level of certain organochlorine pesticides is associated with the development of chronic kidney disease of unknown etiology.

CYP2D6*2 Polymorphism as a Predictor of Failed Outpatient Tramadol Therapy in Postherpetic Neuralgia Patients.

Human cytochrome P4502D6 (CYP2D6) gene is highly polymorphic, leading to wide interindividual ethnic differences in CYP2D6-mediated drug metabolism. Its activity ranges from complete deficiency to excessive activity, potentially causing toxicity of the medication or therapeutic failure with recommended drug dosages. The aim of the study was to find the association of CYP2D6*2 polymorphisms with demographic characters (age, sex, and weight), pain intensity scales [numerical rating scale (NRS) sleep, global perceived effect (GPE)], and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol. The study comprised 246 patients [including 123 nonresponders (NRs) and 123 responders (Rs)] with PHN undergoing analgesic treatment at the pain clinic, Out Patient Department, University College of Medical Sciences, Guru Teg Bahadur Hospital, Delhi, India. Patients with any history of diabetes mellitus, human immunodeficiency virus, malignancy, hematological or liver disease, psychiatric illness, alcohol abuse, and tramadol sensitivity were excluded from the study. The NRSs of (resting and movement), NRS-sleep, and GPE were evaluated by the treating physician. Adverse drug effects during the time of the study were recorded. All samples were analyzed for CYP2D6*2 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The genotype distribution did not vary significantly among genders [NR (P = 0.723); R (P = 0.947)] and different age groups in NRs (P = 0.763) and Rs (P = 0.268). Clinically, statistically significant (P < 0.001) results were obtained in both the groups when compared with baseline in the NRS-sleep and GPE scores, whereas no association was found between NRS-sleep and GPE scores when compared with CYP2D6*2 genotype (P > 0.05). In addition, CYP2D6*2 genotype was not related to the adverse effects of analgesic therapy. The overall results suggested that CYP2D6*2 polymorphism plays no role in the PHN patients receiving tramadol treatment. The CYP2D6*2 polymorphism may not be a predictor of treatment outcome of patients with respect to PHN-receiving tramadol.

Effect of Low Level Subchronic Microwave Radiation on Rat Brain.

OBJECTIVE: The present study was designed to investigate the effects of subchronic low level microwave radiation (MWR) on cognitive function, heat shock protein 70 (HSP70) level and DNA damage in brain of Fischer rats. METHODS: Experiments were performed on male Fischer rats exposed to microwave radiation for 90 days at three different frequencies: 900, 1800, and 2450 MHz. Animals were divided into 4 groups: Group I: Sham exposed, Group II: animals exposed to microwave radiation at 900 MHz and specific absorption rate (SAR) 5.953 × 10-4 W/kg, Group III: animals exposed to 1800 MHz at SAR 5.835 × 10-4 W/kg and Group IV: animals exposed to 2450 MHz at SAR 6.672 × 10-4 W/kg. All the animals were tested for cognitive function using elevated plus maze and Morris water maze at the end of the exposure period and subsequently sacrificed to collect brain tissues. HSP70 levels were estimated by ELISA and DNA damage was assessed using alkaline comet assay. RESULTS: Microwave exposure at 900-2450 MHz with SAR values as mentioned above lead to decline in cognitive function, increase in HSP70 level and DNA damage in brain. CONCLUSION: The results of the present study suggest that low level microwave exposure at frequencies 900, 1800, and 2450 MHz may lead to hazardous effects on brain.