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Background: Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer.Methods: 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat.Findings: Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity.Interpretation: Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer. [ABSTRACT FROM AUTHOR]

Migraine is a globally prevalent neurological disorder. Amitriptyline, a tricyclic antidepressant, has shown potential as a prophylactic treatment for migraine; however, its role as a first-line medication has been debated. A modified Delphi method was used to develop consensus statements on migraine and its management. The literature review identified knowledge gaps, and two survey rounds were conducted among a panel of experts. Consensus was reached for 12 out of 23 initial survey questions, whereas no consensus was reached for four questions after the deliberation in the second round. The results showed that migraine is highly prevalent among women aged 15-35 years in India. Amitriptyline is an effective monotherapy for prophylactic migraine management, with a recommended initial dose of 5-10 mg. A gradual titration over six months achieves optimal results. Amitriptyline is also safe for managing catamenial migraine and can be used at lower doses during pregnancy to alleviate symptoms. The outcomes of this study emphasize that amitriptyline should be considered as a primary prophylactic treatment for migraine because of its efficacy and safety. The evidence-based consensus achieved is intended to serve as guidance for healthcare practitioners in India, and it is anticipated that such adoption will lead to improvement in patient outcomes and an enhancement in the quality of life for those affected by migraines., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Singh et al.)

Introduction: RNF213 mutations have been reported mostly in moyamoya disease (MMD) with varying frequencies across different ethnicities. However, its prevalence in non-MMD adult-onset ischemic stroke is still not well explored., Aims and Objectives: This present study thus aims to screen the most common RNF213 variant (Arg4810Lys, among East Asians) in the Eastern Indian non-MMD ischemic stroke patients and correlate it with long-term progression and prognosis of the patients. The subjects were analyzed for this variant using PCR-RFLP and confirmed using Sanger sequencing method., Result and Conclusion: We have identified Arg4810Lys variant among eleven young-onset familial ischemic stroke patients in heterozygous manner. A positive correlation of the variant with positive family history (P = 0.001), earlier age at onset (P = 0.002), and history of recurrent stroke (P = 0.015) was observed. However, the carriers showed better cognitive performances in memory (P = 0.042) and executive function (P = 0.004). Therefore, we can conclude that Arg4810Lys/RNF213 - a pathogenic variant for young-onset familial ischemic stroke with higher incidence of recurrent events unlike in MMD cases, have no additional impact on cognition among Eastern Indians., (© 2023. Fondazione Società Italiana di Neurologia.)

Post-stroke cognitive impairment (PSCI) is a clinical outcome in around 30% of post-stroke survivors. BDNF is a major gene in this regard. It is regulated by circadian rhythm. The circadian genes are correlated with stroke timings at molecular level. However, studies suggesting the role of these on susceptibility to PSCI are limited. We aim here to determine: (a) genetic risk variants in circadian clock genes, BDNF and (b) dysregulation in expression level of CLOCK, BMAL1, and BDNF that may be associated with PSCI. BDNF (rs6265G/A, rs56164415C/T), CLOCK (rs1801260T/C, rs4580704G/C), and CRY2 (rs2292912C/G) genes variants were genotyped among 119 post-stroke survivors and 292 controls from Eastern part of India. In addition, we analyzed their gene expression in Peripheral blood Mononuclear cells (PBMC) from 15 PSCI cases and 12 controls. The mRNA data for BDNF was further validated by its plasma level through ELISA (n = 38). Among the studied variants, only rs4580704/CLOCK showed an overall association with PSCI (P = 0.001) and lower Bengali Mini-Mental State Examination (BMSE) score. Its 'C' allele showed a correlation with attention deficiency. The language and memory impairments showed association with rs6265/BDNF, while the 'CC' genotype of rs2292912/CRY2 negatively influenced language and executive function. A significant decrease in gene expression for CLOCK and BDNF in PBMC (influenced by specific genotypes) of PSCI patients was observed than controls. Unlike Pro-BDNF, plasma-level mBDNF was also lower in them. Our results suggest the genetic variants in CLOCK, CRY2, and BDNF as risk factors for PSCI among eastern Indians. At the same time, a lowering expression of CLOCK and BDNF genes in PSCI patients than controls describes their transcriptional dysregulation as underlying mechanism for post-stroke cognitive decline., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The present field study evaluates the health status of the catfish Clarias batrachus reared in coal mine effluent (CME)-fed pond water at Rajrappa mining complex using biochemical, haematological and histopathological parameters. Simultaneously, risk assessment along with recovery response of the CME intoxicated fish following their treatment with CME-free freshwater was also studied. The CME-fed pond water fish revealed significant decrease in biomolecules concentrations and considerable increase in activities of several enzymes along with metallothionein level as compared to control. The impaired regulation of metabolic function was also revealed by blood parameters showing significant decrease in haemoglobin content (8.78 ± 0.344 g/100 mL) and red blood cells count (1.77 ± 0.12 × 10 6 mm 3 ) while substantial elevation in white blood cells (187.13 ± 9.78 × 10 3 mm 3 ). The histopathological study also confirmed the changes including hypertrophy of club cells of skin, swelling of secondary lamella of gills, extensive fibrosis in liver and glomerular shrinkage with increased Bowman's space in kidney. Potential health risk assessments based on estimated daily intake and target hazard quotient indicated health risks associated with the consumption of such fishes. The CME-contaminated fish when transferred to CME-free freshwater exhibited decreased metal content accompanied by eventual recovery response as evident by retrieval in biochemical and haematological parameters. Withdrawal study also revealed restoration in the activity of different marker enzymes in fish tissues including blood as well as recovery in their cellular architecture. The results of the present study validate the depuration process as an effective practice for detoxification of fish contaminated with effluent., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the present study, a multi-biomarker approach was used to assess the toxicity of the coal mine effluent (CME) generated at the Rajrappa coal mine on the catfish Clarias batrachus. A core of biomarkers indicative of nutritional value, oxidative stress, and histopathology was selected to illustrate the toxic effects of CME-containing different heavy metals and other toxicants. The results of metal bioaccumulation in CME-exposed fish tissues revealed the highest metal concentration in liver (1.34-297.68 mg/kg) while lowest in muscles (1.47-23.26 mg/kg) as compared to other tissues and so was the metallothionein level. The high value of bioaccumulation observed in liver, kidney, and gills reflects their affinity for metals. In addition, the values of metal pollution index (MPI) of different fish tissues further affirmed that liver followed by kidney and gills are at greater risk than brain, skin, and muscles. Significant alterations in the activity of certain enzymes (aspartate amino transferase, alanine amino transferase, alkaline phosphatase) as well as oxidative stress markers (superoxide dismutase, catalase and lipid peroxidation) were detected in the tissues of CME-exposed fish. The tissue-specific metal accumulation and increased metallothionein levels may be associated with the biochemical and physiological activity of an organ and its constitutive antioxidant defenses. The histopathological changes in the various tissues of the CME-exposed fish justify the high metal accumulation and biochemical alterations. Overall results indicate that the Rajrappa coal mine effluent is very toxic having adverse health impact on the fish and might also affect the human health when consumed.

Introduction: GBA mutations have been reported in PD, PDD and DLB - but not associated with cognitive impairment for example in PSP, AD or MSA. However, frequencies of GBA mutations are ethnicity dependent. The present study aims to identify commonly reported GBA mutations (mostly from Asia), among eastern Indian patients with neurodegenerative disorders., Methods: The patient cohort consisting of 198 classical PD cases, 136 PD cases with cognitive impairment, 184 cases with Parkinson Plus syndrome, 46 AD and 241 unrelated controls, from eastern India. Subjects were analyzed for IVS2 + 1A > G, p.Arg120Trp, p.His255Gln, p.Arg257Gln, p.Glu326Lys, p.Asn370Ser, p.Asp409His, p.Leu444Pro, & RecNciI by PCR-RFLP techniques and confirmed by Sanger sequencing method., Results: We have identified only p.Leu444Pro variant among nine cases; three PDD, one DLB, two PD, two PSP and one AD patients in heterozygous condition. The highest frequency for p.Leu444Pro variant was found among PDD subgroup (3.95 %, P = 0.0134). An overall significant overrepresentation of positive family history (P = 0.000049), impaired recent memory (P = 0.0123) was observed among p.Leu444Pro carriers. Further, subgroup analysis for PD, PD-MCI and PDD, revealed statistically significant higher frequency of early age at onset (P = 0.0455), positive family history (P = 0.0025), higher UPDRS III score (off state) (P = 0.006), advanced H&Y stage (P = 0.045) and anxious behaviour (P = 0.0124) among p.Leu444Pro positive patients., Conclusion: The p.Leu444Pro mutation of GBA was found in patients with PD, PDD, DLB, PSP and AD. An Overall higher frequency of positive family history and impaired recent memory are significantly associated with for p.Leu444Pro carriers from eastern India. Our study also ascertains contribution of p.Leu444Pro to an earlier onset of PD, PD-MCI and PDD, higher UPDRS III score (off state) against positive family history background. Furthermore, taking into consideration other Indian studies, we can conclude that p.Leu444Pro mutation plays a limited role in PD and other neurodegenerative disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Metalloproteins utilizes cellular metals which plays a crucial function in brain that linked with neurodegenerative disorders. Parkinson's disease (PD) is a neurodegenerative disorder that affects geriatric population world-wide. Twenty-four metal-binding protein networks were investigated to identify key regulating protein hubs in PD blood and brain. Amongst, aluminum, calcium, copper, iron, and magnesium protein hubs are the key regulators showing the ability to classify PD from control based on thirty-four classification algorithms. Analysis of these five metal proteins hubs showed involvement in environmental information processing, immune, neuronal, endocrine, aging, and signal transduction pathways. Furthermore, gene expression of functional protein in each hub showed significant upregulation of EFEMP2, MMP9, B2M, MEAF2A, and TARDBP in PD. Dysregulating hub proteins imprint the metal availability in a biological system. Hence, metal concentration in serum and cerebrospinal fluid were tested, which were altered and showed significant contribution towards gene expression of metal hub proteins along with the previously reported PD markers. In conclusion, analyzing the levels of serum metals along with the gene expression in PD opens up an ideal and feasible diagnostic intervention for PD. Hence, this will be a cost effective and rapid method for the detection of Parkinson's disease.

Background & Objectives: Parkinsonian disorder, including Parkinson's disease (PD), is an aetiologically complex neurodegenerative disorder. Mutations in leucine-rich repeat kinase 2 (LRRK2) gene have been implicated in an autosomal dominant form of PD with variable penetrance. The identification of a common LRRK2 variant (p.Gly2019Ser) in dementia with Lewy bodies indicated its potential role in Parkinsonian disorder. The current study was aimed to identify the p.Gly2019Ser variant in Indian patients with Parkinsonian disorder., Methods: The patient group consisting of 412 classical PD patients, 107 PD patients with cognitive impairment, 107 patients with Parkinson plus syndrome and 200 unrelated controls were recruited from eastern part of India. The allele representing p.Gly2019Ser variant was screened by polymerase chain reaction followed by restriction fragment length polymorphism analysis., Results: The p.Gly2019Ser variant was identified in an East Indian young-onset female PD patient in a heterozygous state having several motor and autonomic problems without disturbed cognition. Her younger brother, sister and elder son harbouring the same mutation were asymptomatic carriers for the variant. However, the influence of DNM3 on decreased disease onset in this family was not clear., Interpretation & Conclusions: Identification of the p.Gly2019Ser variant in only one patient among a large number of Indian patients (n=626) with Parkinsonian disorder in our study suggests a limited role of the LRRK2 variant towards disease pathogenesis., Competing Interests: None

Besides clinical and imaging techniques, there is a lack of molecular makers for the diagnosis of Parkinson's disease (PD). There is an immense need to develop biomarkers associated with the phenotypes which may be valuable for individualized treatment. Single-nucleotide polymorphisms (PARK2: Ser167Asn (G>A) and Val380Leu (G>C); PARK7: IVS4 + 46G>A and IVS4 + 30T>G) in PD-related genes were examined to elucidate its relationship with concentration of serum elements and clinical symptoms of PD. A total of 214 PD patients and 213 controls from Indian population were genotyped using PCR and DNA sequencing methods. The serum element concentrations were detected and clinical symptoms were determined based on UPDRS scale and recorded at the time of sample collection. The IVS4 + 30T>G, Ser167Asn (G>A) and Val380Leu (G>C) polymorphisms appeared to alter element concentrations in PD. The patients with Ser167Asn polymorphism showed significant association with copper, iron and zinc that reinforces the role of A allele as a factor for change in the concentrations of elements, than those patients with G allele. In particular, patients with A allele of Ser167Asn have risk of having high serum iron concentration (OR 11.55, 95% CI 5.59-23.85), which are associated with dementia and postural imbalance. Similar results were observed for Val380Leu (G>C) and IVS4 + 30T>G polymorphisms which suggest their role in element concentration and neurological symptoms. Overall, our study demonstrates the influence of polymorphisms of PD genes on element concentrations and clinical symptoms. Results of this study may be taken into account when considering the contributing factors for PD symptoms.

Coal mining generates huge quantity of toxic effluent which consistently pollutes the neighboring wetlands where the local inhabitants regularly cultivate edible fishes. In the present study the concentration of heavy metals Fe, Zn, Cu, Mn, Ni, Cd, Pb and Cr were analyzed in the water and various tissues of edible catfish Clarias batrachus reared in a pond receiving effluents from Rajrappa coal mine, Jharkhand, India. The metal concentrations in the pond water were dramatically higher (Fe 350%, Zn 423%, Cu 12%, Mn 7029%, Ni 713%, Cd 1700%, Pb 4333% and Cr 588%) than the safe limit of Environmental Pollution Agency (2003) as well as the control tap water. Excessive amounts of metals in effluent caused their substantial transfer to the different tissues of the catfish reared in such ponds. Results showed that accumulation of metals in fish tissues were in the following order: liver > kidney > air breathing organ (ABO) > gills > skin > brain > muscles. Among the various tissues the highest accumulation of most of the metals was recorded in the liver (2.05-271.28 mg/kg dry weight) and lowest in the muscles (1.39-30.27 mg/kg dry weight), while the concentration of metals in other tissues ranged in between. The accumulation of heavy metals in tissues appears to cause remarkable histopathological alterations in skin, gills, ABO, liver and kidney that might be leading to deleterious effect on fish physiology and consequently impact the consumers of such fishes.

In the present study, three aquatic macrophytes, Eichhornia crassipes, Salvinia molesta, and Pistia stratiotes were used to assess their relative efficacies in decontamination of a fish culture pond, regularly fed with coal mine effluent (CME). The level of metals like Fe, Mn, Ni, Zn, Cu, Pb, Cr, and Cd were much higher in CME-fed pond water than their recommended limits in drinking water set by the Bureau of Indian standards and in effluents by the Environmental Protection Agency. The levels of metal were lowered substantially in CME-fed pond water after exposure of the above plants to such water, however, metal levels in the plants increased tremendously. The increased metal levels in plants severely damaged their physiological and biochemical processes. The contents of chlorophyll a, b and carotenoid were reduced by 63.2, 64.2, and 46.3%, respectively, in E. crassipes , 41, 57.4, and 57.8% in S. molesta , and 42, 62, and 61% in P. stratiotes . The accumulating metals also generated oxidative stress in plants, as evident from the increased superoxide dismutase and catalase activities and enhanced malondialdehyde content. The E. crassipes was the most potent in absorbing the metals from the CME-fed pond water, followed by S. molesta and P. stratiotes .

Background: Headache is common in communities; however, epidemiological research regarding its prevalence is infrequent in India., Aim: We planned to study the prevalence of migraine, its disease burden, and the associated risk factors., Setting and Design: This is an urban community study conducted in Kolkata with a cross-sectional and nested case-control design., Materials and Methods: The criteria to study headache among a representative sample (aged 20-50 years) was based on the International Classification of Headache Disorders-II. Sex- and age-matched controls without headache were evaluated for putative risk factors. The disease burden was measured as disability adjusted life years (DALY)., Results: Screening of 2421 individuals revealed that the 1-year prevalence of migraine was 14.12%. Education, environmental exposure, travel, and oral contraceptives determine approximately 75% of the underlying risks. DALY showed maximum burden among women in the age range of between 30 and 34 years., Conclusion: The community-based prevalence of migraine in India is similar to that observed in other countries except Africa. The burden was maximum among women. The risk factors responsible for migraine should be addressed and institution of public health measures are warranted.

Toxicity of the effluent generated at the Rajrappa coal mine complex under the Central Coalfields Limited (CCL, a subsidiary of Coal India Limited) in Jharkhand, India was investigated. The concentrations (mg L -1 ) of all the toxic metals (Fe, Mn, Ni, Zn, Cu, Pb, Cr, and Cd) in the coal mine effluent were above the safe limit suggested by the Environmental Protection Agency (EPA 2003). Among these, Fe showed the highest concentration (18.21 ± 3.865), while Cr had the lowest effluent concentration (0.15 ± 0.014). Efforts were also made to detoxify the effluent using two species of aquatic macrophytes namely "'Salvinia molesta and Pistia stratiotes." After 10 days of phytoremediation, S. molesta removed Pb (96.96%) > Ni (97.01%) > Cu (96.77%) > Zn (96.38%) > Mn (96.22%) > Fe (94.12%) > Cr (92.85%) > Cd (80.99%), and P. stratiotes removed Pb (96.21%) > Fe (94.34%) > Ni (92.53%) > Mn (85.24%) > Zn (79.51%) > Cr (78.57%) > Cu (74.19%) > Cd (72.72%). The impact of coal mine exposure on chlorophyll content showed a significant decrease of 42.49% and 24.54% from control values in S. molesta and P. stratiotes, respectively, perhaps due to the damage inflicted by the toxic metals, leading to the decay of plant tissues.

Objectives: Increase in aging population is expected to lead to increasing prevalence of dementia in India. In this study, we aimed to determine prevalence, incidence, and mortality of dementia and its subtypes and assess dementia burden in terms of disability-adjusted life years (DALY)., Methods: A community study was conducted over 5 years (2003-2008) in Kolkata, India, on 100,802 (males 53,209) randomly selected subjects to assess prevalence and capture data on incident cases and deaths. Standard case definitions were used. The data were used to estimate years of life lost (YLL) due to premature mortality, years of life lived with disability (YLD), and DALY, based on Global Burden of Disease 2010 approach., Results: During 2003-2004, there were 103 (men 55) cases of dementia. The prevalence was 1.53% (age adjusted 1.12%) at age ≥65 years. In those ≥55 years age, average annual incidence rate of dementia was 72.57 per 100,000. All-cause standardized mortality ratio in dementia cases was 4.74 (men 6.19, women 3.03). The burden of dementia in 2007-2008 revealed that overall YLL was 47.13 per 100,000 and YLD ranged from 1.87 to 16.95 per 100,000 depending on the clinical severity of dementia. The overall DALY lost per 100,000 due to dementia for the year 2007-2008 was 74.19., Conclusions: This community study revealed a low prevalence and incidence of dementia with consequent low DALY-derived burden of illness compared with many industrialized nations. YLL formed major component of DALY indicating premature mortality to be an outcome of dementia burden. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Parkinson's disease (PD) is a neurodegenerative disease with the absence of markers for diagnosis. Several studies on PD reported the elements imbalance in biofluids as biomarkers. However, their results remained inconclusive. This study integrates metallomics, multivariate and artificial neural network (ANN) to understand element variations in CSF and serum of PD patients from the largest cohort of Indian population to solve the inconsistent results of previous studies. Also, this study is aimed to (1) ascertain a common element signature between CSF and serum. (2) Assess cross sectional element variation with clinical symptoms. (3) Develop ANN models for rapid diagnosis. A metallomic profile of 110 CSF and 530 serum samples showed significant variations in 10 elements of CSF and six in serum of patients compared to controls. Consistent variations in elements pattern were noticed for Calcium, Magnesium and Iron in both the fluids of PD, which provides feasible diagnosis from serum. Furthermore, implementing multivariate analyses showed clear classification between normal and PD in both the fluids. Also, ANN provides 99% accuracy in detection of disease from CSF and serum. Overall, our analyses demonstrate that elements profile in biofluids of PD will be useful in development of diagnostic markers for PD.

Ganga River, life line of millions of people got heavily polluted due to uncontrolled anthropogenic activities. To monitor the effect of pollution of the river on its aquatic life, a field study was conducted by analyzing the different biomarker enzymes and biochemical parameters in the various tissues (muscles, liver, gills, kidney, brain, and skin) of the Indian major carp Labeo rohita collected from the River Ganga from different study sites of Varanasi district. Activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, and level of lipid peroxidation were found to be higher in the fish collected from the river showing pollutant-induced oxidative stress in the fish. Disturbed health status of the river fish was also manifested by increased activities of aspartate amino transferase, alanine amino transferase, and alkaline phosphatase. Concentration of nutritionally important biomolecules (proteins, lipids, and moisture) and energy value were also found to be significantly lower in the tissues of the River fish indicating its decreased nutritional value due to oxidative stress caused by different pollutants.

Background: The rising incidence of stroke in India indicates the importance of evaluating the existing knowledge, attitude, and practice (KAP) in the community, which is essential for stroke control., Objective: To explore and compare stroke-related KAP among participants from stroke-affected families (SAFs) and nonstroke-affected families (NSFs)., Design: Using stratified random sampling, a three-phase house-to-house survey was conducted in Kolkata, West Bengal, India. First, field investigators screened subjects of stroke; second, the neurologist confirmed positive cases; and third, under supervision of the neuropsychologist, a validated questionnaire on KAP was administered to participants from SAFs and age-matched NSAFs from the same neighborhood., Results: The KAP questionnaire was administered to 282 participants each from both groups. Knowledge about stroke prevailed in 97% participants and was significantly higher in the SAF group. Both SAF and NSAF groups had better knowledge about prominent symptoms of stroke (loss of consciousness and paralysis) and admitted it as emergency situation requiring hospitalization and that it was potentially preventable. Those persons belonging to the SAF group, however, had lesser knowledge of the risk factors such as diabetes (P < 0.001), smoking (P < 0.014), alcoholism (P < .0.0001), family history (P < .0.0001) and mild stroke symptoms such as headache, (P < 0.001), vomiting (P < 0.001), and fits (P 0.003) as compared to the NSAF group., Conclusions: Persons from both SAF and non-SAF groups are aware about stroke but possess lesser knowledge about the many symptoms of stroke and risk factors, indicating the necessity of enhancement of existence knowledge on symptoms for better diagnosis and of risk factors for better prevention.

Purpose: Cancer-related dyspnea is a common, distressing, and difficult-to-manage symptom in cancer patients, resulting in diminished quality of life and poor prognosis. Buspirone, a non-benzodiazepine anxiolytic which does not suppress respiration and has proven efficacy in the treatment of generalized anxiety disorder, has been suggested to relieve the sensation of dyspnea in patients with COPD. The main objective of our study was to evaluate whether buspirone alleviates dyspnea in cancer patients., Methods: We report on a randomized, placebo-controlled trial of 432 patients (mean age 64, female 51%, lung cancer 62%) from 16 participating Community Clinical Oncology Program (CCOP) sites with grade 2 or higher dyspnea, as assessed by the Modified Medical Research Council Dyspnea Scale. Dyspnea was assessed by the Oxygen Cost Diagram (OCD; higher scores are better) and anxiety by the state subscale of the State-Trait Anxiety Inventory (STAI-S; lower scores are better) at baseline and after the 4-week intervention (post-intervention)., Results: Mean scores from baseline to post-intervention for buspirone were OCD 8.7 to 9.0 and STAI-S 40.5 to 40.1 and for placebo were OCD 8.4 to 9.3 and STAI-S 40.9 to 38.6 with raw improvements over time on both measures being greater in the placebo group. Analysis of covariance (ANCOVA) controlling for baseline scores showed no statistically significant difference between groups for OCD (P = 0.052) or STAI-S (P = 0.062)., Conclusion: Buspirone did not result in significant improvement in dyspnea or anxiety in cancer patients. Thus, buspirone should not be recommended as a pharmacological option for dyspnea in cancer patients.

The impact of sublethal toxicity of sodium arsenite on hematological and certain biochemical parameters of the fresh water catfish Clarias batrachus has been analyzed following exposure of sublethal concentration (1 mg/L; 5% of LC 50 value) of sodium arsenite for 10, 30, 45, and 60 days. Arsenic bioaccumulation in the blood tissue of the fish increased progressively with increased period of exposure. The values of total erythrocyte count (TECs), total leucocytes count (TLCs), hemoglobin concentration, and packed cell volume (PCV) 1.40 ± 0.03 × 10 6 /mm 3 , 174.83 ± 2.74 × 10 3 /mm 3 , 5.01 ± 0.26 g/100 ml, 25.00 ± 1.06 were observed respectively at the end of 60 days of exposure. The results of hematological indices were found to be 179.23 ± 8.81fl/cell for mean corpuscular volume (MCV), 35.92 ± 1.89 pg/cell for mean corpuscular hemoglobin (MCH) and 20.17 ± 1.12 g/dl for mean corpuscular hemoglobin concentration (MCHC). The present findings are clearly indicating severe fish anemia due to the arsenic salt exposure. The continued arsenic toxicity results in decreased serum protein concentration that might be a cause for the loss of weight as well as weakness in the fish.

Currently, the stroke incidence in India is much higher than Western industrialized countries. Large vessel intracranial atherosclerosis is the commonest cause of ischemic stroke in India. The common risk factors, that is, hypertension, diabetes, smoking, and dyslipidemia are quite prevalent and inadequately controlled; mainly because of poor public awareness and inadequate infrastructure. Only a small number of ischemic stroke cases are able to have the benefit of thrombolytic therapy. Benefits from stem cell therapy in established stroke cases are under evaluation. Presently, prevention of stroke is the best option considering the Indian scenario through control and/or avoiding risk factors of stroke. Interventional studies are an important need for this scenario.

Aim was to analyze predictors of burden among primary caregivers (CGs) of Indian Parkinson's disease (PD) patients. 150 PD patients were administered using Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr Scale (H&Y), Montgomery Asberg Depression Rating Score (MADRS) and Mini Mental State Examination (MMSE) in this cross-sectional evaluation study. CG burden was assessed by Caregiver's Burden Scale (CBS), Hospital Anxiety and Depression Scale (HADS), SF-36 and 20-item Burden Assessment Schedule (BAS). Linear regression methods were used to evaluate factors contributing to burden and stress. Mean age of CG was 50.38±16.04 (range: 25-83 yrs). Marital status of CGs was noted to have significant relationship with CBS score (F=9.525, P<0.0001). Siblings (brother/sister) reported the highest CBS score while the wives reported the least. Correlations were strong between CBS and HADS anxiety (r=0.228, P=0.0048) and HADS depression (r=0.2172, P=0.0076). High correlations were found in caregiving duration, patients' stage of illness and motor disability among all the scales (CBS, HADS, SF36) determined. Step-wise regression analysis showed UPDRS (beta=1.364-0.202 ranging among all scales) and H&Y stages (beta=2.786-7.257) to have the strongest influence on CGs. CGs of patients with depression (MADRS: P=0.007 (SF36 mental) and dementia (MMSE: P=0.01) experienced greater stress. Social and financial status was disrupted in ~60% to 80% of the CGs. Motor imbalances with disability of PD patients and severity of disease are the main factors contributing to burden and stress in CGs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Disability-adjusted life year (DALY) is a time-based measure of disease burden incorporating both disability and mortality. Our study aimed to determine the DALY lost from epilepsy in an Indian metropolis., Methods: A population-based prospective study on epilepsy was conducted over 5 years (2003-8) in Kolkata, India, on randomly selected 100,802 subjects (males 53,209, females 47,593) to assess prevalence as well as to capture incident cases of epilepsy and those incident cases that died. Standard case definitions were used. The data were used to estimate years of life lost (YLL) due to premature mortality, years of life lived with disability (YLD), and DALY, utilizing the prevalence-based Global Burden of Disease (GBD) 2010 approach. Age- and gender-specific figures were computed., Results: During 2003-2004, a total of 476 subjects with active epilepsy were detected and the age-adjusted prevalence rate was 4.71 per 1000. Over 5 years, there were 197 incident cases of epilepsy of whom 26 died. The age-adjusted annual incidence rate of epilepsy was 38.3 per 100,000. The all-cause standardized mortality rate (SMR) of epilepsy was 2.4. The burden of epilepsy in the year 2007-8 revealed the overall YLL was 755 per 100,000, and the overall YLD ranged from 14.45 to 31.0 per 100,000 persons depending on the clinical severity of the epilepsy. Both YLL and YLD values were higher in males than in females. The overall DALY lost due to epilepsy in 2007-8 was found to be 846.96 (males 1183.04, females 463.81) per 100,000., Conclusions: This is the first study in India to determine the DALY of epilepsy using GBD 2010. The results reveal a substantial burden of epilepsy in our setting. Similar such studies are needed in other parts of India in both urban and rural settings., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Little information is available regarding the molecular pathogenesis of Parkinson's disease (PD) among the Bengalee population in West Bengal, India. This study was undertaken to determine the contribution of Parkin variants in well-defined ethnically identical Bengalee population of India and further to describe the clinical spectrum associated with these mutations. A total of 150 unrelated PD patients and 150 controls were recruited for the study. The entire cohort was screened for mutations in all the 12 exons of the gene along with flanking splice junctions by polymerase chain reaction and DNA sequencing. Eleven nucleotide variants including two novel changes were detected. Cerebrospinal fluid (CSF) parkin protein expression of the novel mutation, Val186Ile (found in heterozygous condition in one patient only) was almost 2.7 folds lower than the controls and other PD patients. Molecular characterization of polymorphisms Ser167Asn and Val380Leu depicted that homozygous Ser167 and Val380 are significantly associated with the disease. We did not find any linkage disequilibrium among the SNPs, the low r(2) for every pair of single-nucleotide polymorphisms (SNPs) indicated that these SNPs cannot be tagged by each other. Another novel intronic change, IVS8+48C>T was present in almost equally in PD patients and controls. Among the ethnically defined Bengalee population of West Bengal, occurrence of Parkin mutation is 4% (6/150) of the PD patient pool supported with decreased folds of expression of CSF PARKIN protein. Parkin polymorphisms, Ser167 and Val380 are risk factors for the progression of the disease, and their frequency is greatly influenced by ethnic origin.

Stroke survivors (SS) are rising with higher incidence of stroke in developing countries. In addition to physical impairment, other factors such as cognition, social interaction, and depression determine the functional outcome after stroke. Considering the paucity of data from developing countries, we planned to determine the change in various functional parameters among SS. This community-based prospective study was carried out in Kolkata, India among 283 SS between 2006 and 2010. Functional outcome was assessed at baseline and at 3 annual follow-up visits using validated tools. A stepwise regression analysis was performed with demographic and stroke-related covariates against various measures of functional outcome. Result showed that mean Barthel Index score at baseline was 76.4 ± 30.8. Bengali version of mental status examination and Geriatric Depression Scale scores trended down over time with a negative regression coefficient of -.2061 (standard error [SE], .0937) and -.4488 (SE, .2145). Other outcomes did not change. Female gender, depression, and cognitive dysfunction had an unfavorable impact, whereas education correlated positively. In conclusions female gender and neuropsychiatric disturbances showed poor functional outcome compared with education, which correlates with better outcome. This information will be helpful for patients in developing countries for planning stroke rehabilitation., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Depression and cognitive impairment are frequent manifestations in Parkinson's disease (PD). Although a few longitudinal studies have reported on depression and dementia in PD, there is a yet a lack of such studies in India. This 7-year longitudinal study is a hospital-based prospective case (n = 250)-control (n = 280) study. In all, 36.8% had PD with no cognitive impairment (PD-Normal), 27.2% of the patients with PD were affected by dementia (PDD), and 36% of the remaining patients with PD had mild cognitive impairment (PD-MCI) at baseline. After 7 years of evaluation, 32 new patients, 12 patients from the PD-MCI group and 9 patients from the PD-Normal group, were diagnosed with dementia. The 7-year prevalence rate for dementia was estimated to be 49.28%. In the Indian population, an early onset of dementia is noted among patients with PD, with the age of onset being less than 55 years. Patients with early-onset PDD showed depression symptoms that differed significantly from the controls of the same age-group. There was a major difference in verbal fluency, word list recall, constructional praxis and recall, word list recognition, abridged Boston Naming Test, word list memory with repetition, and Mini-Mental State Examination between PD-MCI and PDD groups. Hallucinations before baseline (odds ratio [OR] = 4.427, 95% confidence interval [CI] = 2.122-9.373), akinetic/tremor dominancy (OR = 0.380, 95%CI = 0.149-0.953), and asymmetrical disease onset (OR = 0.3285, 95%CI = 0.1576-0.685) can be considered as risk factors for patients with dementia. Patients with early-onset PD might be more prone to complex depression and dementia. As the disease progresses, akinetic-dominant PD, early hallucinations, and asymmetrical disease onset are the potential risk factors for the development of dementia in patients with PD., (© The Author(s) 2014.)

The frequency of cognitive dysfunction among community stroke survivors (SS) is not known in India. This prospective study investigated the prevalence of poststroke mild cognitive impairment (psMCI) and poststroke dementia (psDem), the annual progression rate to dementia, and pertinent risk factors in a sample population of SS in Kolkata, India between September 2006 and July 2010. From a community-based stroke registry, 281 SS were assessed at baseline year after excluding attrition due to various causes. Validated cognitive tools were applied by trained field workers under supervision of a neuropsychologist. The assessment was repeated annually for consecutive three years. The mean follow-up period was 1.89 years (range, 1-3 years). The period prevalence rate of psDem was 13.88% (95% confidence interval [CI], 9.91%-18.90%) at baseline, and the average annual progression rate to dementia was 3.53% (95% CI, 2.09%-5.58%). Compared with subjects without dementia, those with psDem were significantly older at first-ever stroke and more likely to have cortical atrophy. The period prevalence rate of psMCI was 6.05% (95% CI, 1.45%-13.64%) at baseline, and 10.6% (95% CI, 4.57%-20.88%) of these subjects converted to psDem annually. Survival analysis of psDem patients showed a greater risk of death in psDem SS as compared to nondemented SS (hazard ratio, 2.65; 95% CI, 1.72-6.15). Our data suggest that the overall prevalence of psDem is higher than that of psMCI, possibly related to nonexclusion of prestroke dementia, but that the average annual progression rate of SS to psDem and that of psMCI to psDem are comparable. Older age at first-ever stroke and cortical atrophy are associated with increased risk for dementia among SS., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: Post-stroke depression (PSD) is a disabling entity among stroke survivors (SS). Longitudinal studies on PSD, essential to determine its prognosis, are lacking from developing countries. This prospective study was undertaken to assess the prevalence, natural history, and correlates of depression among SS in an Indian community., Methods: From a community based stroke registry, SS were assessed annually for cognition, disability, and depression using Bengali validated scales. PSD was diagnosed if score on geriatric depression scale was greater than or equal to 21. Complex sample strategy was considered when calculating prevalence of post stroke depression. An age- and sex-matched case-control study was undertaken to determine the odds of depression in SS., Results: Prevalence of PSD was 36.98% (95% confidence interval [CI]: 31.89%-42.06%) among 241 patients assessed at baseline. About 17% developed depression annually and a similar proportion had spontaneous improvement. Peak rate of PSD was beyond 3 months and continued up to 18 months after stroke. Compared to the non-depressed group, PSD subjects were significantly older, had higher age at first stroke, less education, lower socioeconomic status, and greater cognitive impairment and disability. Education had a protective role. Mortality in PSD was nearly twice that in non-depressed patients, though not significant statistically (hazard ratio: 1.84; 95% CI: 0.90-3.77). Compared with controls, odds ratio of PSD was 19.95 (95% CI: 10.09-39.47)., Conclusions: Approximately one-third of SS develop PSD, similar to developed countries. Prevalence remains stable annually. Delayed peak of PSD suggested later realization of underlying disability. Predictors of PSD have been described and higher literacy was protective in this study., (Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Refractory Epilepsy (R.E.) is a condition where all antiepileptic drugs (AEDs) fail to provide adequate seizure control. To diagnose R.E., false cases of refractoriness need to be carefully excluded. There are several predictors of refractoriness. The treatment options in R.E. are resective surgery, ketogenic diet and vagal nerve stimulation. The roles of newer AEDs are also promising. The future therapeutic possibilities include deep brain stimulation, AED containing polymers, stem cells and gene therapy.

A field study was conducted to examine different physicochemical properties of water and various haematological and biochemical parametres of the fish Labeo rohita collected from the Ganga River (National river of India) at Varanasi district, India. The water was found to be greatly contaminated with a number of dissolved metals (Fe, Cr, Zn, Cu, Mn, Ni and Pb) whose concentrations were above the safe limits suggested by Bureau of Indian Standard (BIS 1991) for drinking water (Fe, 1,353.33 %; Cr, 456 %; Mn, 553.33 %; Ni, 4,490 % and Pb, 1,410 %). The metal accumulation in the fish blood was very high (Fe, 2,408 %; Cr, 956.57 %; Zn, 464.90 %; Cu, 310.57 %; Mn, 1,115.48 %) in comparison to the control fish maintained under strict quality control. Lower values of the various haematological parameters (total erythrocytes count, haemoglobin, haematocrit, mean corpuscular volume and O2-carrying capacity) in the river fish in comparison to the control indicate toxic manifestation exerted by the contaminated river water on the fish. The higher level of total leucocytes count further illustrates stressed condition of the river fish. The toxic impact of the Ganga water is also expressed in the fish by the presence of higher levels of cholesterol, glucose, elevated activities of the enzymes aspartate amino transferase and alanine amino transferase, and lowered protein concentration.

In the present paper, accumulation of zinc (Zn), iron (Fe), copper (Cu), chromium (Cr), nickel (Ni), manganese (Mn) and lead (Pb) was determined in different tissues (skin, muscles, liver, gills, kidney and brain) of rohu (Labeo rohita) collected from the River Ganga in Varanasi, India. Concentrations of Cu (except gills), Fe and Cr (except brain for Cr) in most of the tissues were above the permissible safe limits for human consumption suggested by the Food and Agricultural Organization (FAO 1983). Concentrations of all metals were higher in River Ganga fish than those from the University fish farm. With the exception of Zn in skin, muscle and brain tissue, the studied metals were bioaccumulated in all tissues. The total metal accumulation or metal pollution index was highest in liver (20.8 ± 0.50) followed by kidney (16.8 ± 0.44), gills (15.2 ± 0.15), muscles (12.1 ± 0.08), skin (10.5 ± 0.53) and brain (7.0 ± 0.02).

Phytoremediation efficacy of Lemna minor and Azolla pinnata in decontaminating metals from coal mine effluent (CME) was analyzed using bioassays. Catfish Heteropneustes fossilis were exposed to both the phytoremediated CMEs for the metal bioaccumulation analysis and biochemical alteration in seven vital tissues. Gross concentration of metals accumulated in liver, kidneys, air breathing organs (ABO), skin and muscle were greater in fish exposed to A. pinnata remediated CME (AP-CME) than those exposed to L. minor remediated CME (LP-CME). Total protein concentrations of all the tissues were greater in fish exposed to LP-CME than to AP-CME. Glycogen concentrations were greater in muscle, brain, ABO and skin of LP-CME exposed fish. In remaining tissues (liver, kidneys and gills) concentrations of glycogen were more in AP-CME exposed ones. Total lipid and total DNA concentrations were greater in most of the tissues of fish exposed to LP-CME than to AP-CME. The total RNA concentrations were elevated only in muscle, liver, kidneys and brain of LP-CME exposed fish; in rest of the tissues (gills, ABO and skin) it was greater in AP-CME exposed fish. The values of condition factor (K) and organosomatic index (OSI) of fish exposed to LP-CME and AP-CME were insignificant to those of wild fish. However, the improvements in the biomolecules concentration of tissues of fish exposed to either of the phytoremediated effluent were not equivalent to their concentration in the wild fish. Thus, decontamination of CME by either of these macrophytes was not complete and prolonged exposure of even phytoremediated CMEs exerts deleterious effects on the fish., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background/aims: The disability-adjusted life year (DALY) is a new time-based measure of disease burden incorporating both disability and mortality. Our study aims to determine the DALYs lost due to stroke using a direct methodology and the implications., Methods: A population-based, house-to-house, 2-stage, prospective study on stroke was conducted over 7 years in Kolkata, India, on 100,802 randomly selected subjects to capture the incident cases of first-ever stroke and those with fatal stroke. The data were utilized to estimate years of life lost due to premature mortality (YLLs), years lived with disability (YLDs) and DALYs lost., Results: Over 7 years, there were 763 incident cases of first-ever stroke; of these, 320 had a fatal stroke within 30 days and 443 were stroke survivors. The overall DALYs lost due to stroke were computed as 795.57 per 100,000 person-years (730.43 in men and 552.86 in women). The overall YLL and YLD values were 593.14 and 202.43 per 100,000 person-years, respectively. The YLLs comprised 74.5% of the total DALYs., Conclusions: This is the first study in India where DALYs lost due to stroke were derived by a direct method. High YLL values demand urgent measures for controlling premature stroke death., (Copyright © 2013 S. Karger AG, Basel.)

Pattern of arsenic bioaccumulation in six organ systems (blood, brain, gills, liver, muscles and skin) of Clarias batrachus was analysed following exposure to sublethal (1 mg L(-1); 5% of 96 h LC(50) value) concentration of sodium arsenite. After 60 days of treatment the liver accumulated highest concentration (9.711 ± 0.138 μg g(-1) dry wt of tissue.) of arsenic followed by gills (6.156 ± 0.154) > blood (6.070 ± 0.043) > muscles (5.756 ± 0.123) > skin (5.606 ± 0.140) > brain (2.350 ± 0.205). The bioaccumulations of arsenic in all the tissues were time dependant and increased with exposure period. Although the exposed fish loaded with arsenic did not die after prolonged treatment (60 days), the amount of arsenic accumulated made them unsuitable for human consumption. Due to depletion of the proteineous components of their muscles, the body mass of the exposed fish decreased without corresponding decrease in their length. This made the fish lean and thin. These proteineous moieties of the muscles and other tissue systems of the stressed fish were mobilized for breakdown to generate additional requirement of energy to combat the arsenic toxicity.