Immediate Inferior Alveolar Nerve Reconstruction With Ablative Mandibular Resection Results in Functional Sensory Recovery.

BACKGROUND: Ablative mandibular resection with sacrifice of the inferior alveolar nerve (IAN) results in loss of sensation and decreased quality of life. PURPOSE: The purpose of this study is to evaluate functional sensory recovery (FSR) of immediate IAN allograft reconstruction performed during ablative mandibular resection at 1 year following surgery. STUDY DESIGN, SETTING, SAMPLE: This is a single-center retrospective cohort study that included consecutive subjects who underwent mandibular resection with IAN discontinuity and used a nerve allograft of ≥40 mm. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable is the use of an immediate nerve allograft in mandibular reconstruction. MAIN OUTCOME VARIABLE(S): The main outcome variable is FSR at 1 year using the Medical Research Council Scale. COVARIATES: Covariates include subject age, sex, specific pathology, nerve gap length, and development of neuropathic pain. ANALYSES: Statistical analysis of comparison of neurosensory outcomes was measured by bivariate statistics, weighted values, repeated measures, analysis of variance, and McNemar test. RESULTS: The study sample was composed of 164 subjects, of whom 55 (33.5%) underwent nerve allograft reconstruction and 30 (18.3%) did not have nerve reconstruction. Seventy-nine subjects (48.2%) did not meet the inclusion criteria. In the entire nerve allograft group of 55 subjects, FSR was achieved in 80% at 1 year; however, in benign disease alone, 31 of 33 (94%) achieved FSR at 1 year. In the nonallograft group (all benign disease), only 2 of 30 (7%) achieved FSR at 1 year. The significant covariates were age and pathology. Benign pathologic resections were 5.2 times more likely to achieve FSR than malignancies, and all subjects ≤ 18 years of age achieved FSR. After adjusting for age, sex, pathology, nerve gap length, nerve allograft was significantly associated with achieving FSR at 1 year (adjusted odds ratio = 5.52, 95% confidence interval = (1.03, 29.51), P value = .045 < .05). CONCLUSION AND RELEVANCE: Immediate long-span IAN allograft reconstruction is effective in restoration of sensation with an overall 80% of subjects achieving FSR at 1 year, while benign disease resulted in 94% FSR at 1 year. Immediate IAN reconstruction should be considered with mandibular resection involving the IAN, especially for children and benign disease.

Factors associated with lifetime suicide attempts: findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

AIM: To evaluate the risk factors associated with lifetime suicide attempts in bipolar disorder (BD) patients. METHODOLOGY: 773 BD patients with a duration of illness of at least ten years, currently in clinical remission, were evaluated for suicidal attempts in their lifetime. Those with and without lifetime suicide attempt(s) were compared for various demographic and clinical risk factors. RESULTS: 242 (31.3%) patients had a history of at least one lifetime suicide attempt. Compared to those without lifetime suicide attempts, those with suicidal attempts were less educated, were more often females, spent more time in episodes, and had a significantly more number of total episodes (in the lifetime, first five years of illness, and per year of illness), had significantly more number of total depressive episodes (in the lifetime, first five years of illness, and per year of illness), spent more time in depressive episodes, had more severe depressive episodes, more often had depression as the first episode in the lifetime, spent more time in mania/hypomania/mixed episodes, had higher residual depressive and manic symptoms, more often had rapid cycling affective disorder pattern in the lifetime, use of cannabis in dependence pattern, had poorer insight into their illness and had a higher level of disability (especially in three out of the four domains of Indian disability evaluation assessment scale). CONCLUSIONS: About one-third of the patients with BD have at least one-lifetime suicidal attempt, and those with suicide attempts usually have a poorer course of illness.

Neutrino Propagation When Mass Eigenstates and Decay Eigenstates Mismatch.

We point out that the Hermitian and anti-Hermitian components of the effective Hamiltonian for decaying neutrinos cannot be simultaneously diagonalized by unitary transformations for all matter densities. We develop a formalism for the two-flavor neutrino propagation through matter of uniform density, for neutrino decay to invisible states. Employing a resummation of the Zassenhaus expansion, we obtain compact analytic expressions for neutrino survival and conversion probabilities, to first and second order in the "mismatch parameter" γ[over ¯].

Predominant polarity in bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

AIM: This cross-sectional study aimed to assess the predominant polarity (PP) in patients with bipolar disorder (BD) and the factors associated with PP. METHODOLOGY: For this study, 773 participants with at least 10 years of illness, were recruited from 14 centres, were evaluated using the National Institute of Mental Health- Retrospective Life Charts to assess the course of illness and PP was determined by both Barcelona proposal and the Harvard Index. RESULTS: According to Barcelona proposal for PP, 20.6% of the patients belonged to depressive PP, 45.8% belonged to manic PP and 33.6% belonged to indeterminate polarity. According to Harvard index of PP, 31.6% of the patients belonged to depressive PP, 56.1% belonged to manic polarity and 12.3% of the patients could not be categorized into any of these categories and hence, were considered to have indeterminate polarity. Those with depressive PP were more often having BD-II, had later age of onset, spent more time in episodes, had higher residual depressive symptoms, had lower residual manic symptoms, more often had depression as the first lifetime episode, and less often had at least one psychotic episode. CONCLUSION: In the Indian subcontinent, although the prevalence of PP is influenced by the definition used, the most common PP is that of mania.

Is unipolar mania a distinct entity: findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

AIM: This study aimed to evaluate the prevalence of unipolar mania (UM) in a group of patients of bipolar disorder (BD). Additionally, effort was made to evaluate the demographic, clinical and treatment related factors, which distinguish subjects of UM from BD. METHODOLOGY: Seven hundred and seventy-three patients with BD, of at least 10 years duration, recruited from 14 General Hospital Units of tertiary care centers from India were evaluated for UM. RESULTS: The prevalence of UM, varied from 5.4% to 20.3%, depending on the definition used. With the most stringent definition of ≥4 episodes of mania and at least 5 years of follow-up, the prevalence of UM was 5.4%. Compared to patients of BD, who have episodes other than mania too, those with UM had lower proportion of patients with lifetime history of suicide attempts, spent less time in the episodes in their lifetime and had lower severity of residual depressive and manic symptoms. Further, compared to those with episodes other than mania too, those with UM had higher number of manic episodes per year of illness, had higher proportion of patients who had more than five episodes in the lifetime and had higher proportion of those with at least one episode with psychotic symptoms in the lifetime. CONCLUSION: The present study suggests that a small proportion of patients with BD have UM course and this runs a different clinical course compared to that seen in patients with traditionally recognized as BD.

Effect of N,N Coordination and RuII Halide Bond in Enhancing Selective Toxicity of a Tyramine-Based RuII (p-Cymene) Complex.

Ruthenium compounds are promising anticancer candidates owing to their lower side-effects and encouraging activities against resistant tumors. Half-sandwich piano-stool type RuII compounds of general formula [(L)RuII(η6-arene)(X)]+ (L = chelating bidentate ligand, X = halide) have exhibited significant therapeutic potential against cisplatin-resistant tumor cell lines. In RuII (p-cymene) based complexes, the change of the halide leaving group has led to several interesting features, viz., hydrolytic stability, resistance toward thiols, and alteration in pathways of action. Tyramine is a naturally occurring monoamine which acts as a catecholamine precursor in humans. We synthesized a family of N,N and N,O coordinated RuII (p-cymene) complexes, [(L)RuII(η6-arene)(X)]+ (1-4), with tyramine and varied the halide (X = Cl, I) to investigate the difference in reactivity. Our studies showed that complex 2 bearing N,N coordination with an iodido leaving group shows selective in vitro cytotoxicity against the pancreatic cancer cell line MIA PaCa-2 (IC50 ca. 5 µM) but is less toxic to triple-negative breast cancer (MDA-MB-231), hepatocellular carcinoma (Hep G2), and the normal human foreskin fibroblasts (HFF-1). Complex 2 displays stability toward hydrolysis and does not bind with glutathione, as confirmed by 1H NMR and ESI-HRMS experiments. The inert nature of 2 leads to enhancement of cytotoxicity (IC50 = 5.3 ± 1 µM) upon increasing the cellular treatment time from 48 to 72 h.

Modulation of CD11c+ lung dendritic cells in respect to TGF-ß in experimental pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a deadly, progressive lung disease with very few treatment options till now. Bleomycin-induced pulmonary fibrosis (BIPF) is a commonly used mice model in IPF research. TGF-ß1 has been shown to play a key role in pulmonary fibrosis (PF). Dendritic cell (DC) acts as a bridge between innate and adaptive immune systems. The coexistence of chronic inflammation sustained by mature DCs with fibrosis suggests that inflammatory phenomenon has key importance in the pathogenesis of pulmonary fibrosis. Here, we investigated the modulation of DCs phenotypic maturation, accumulation in lung tissue, and expression of other lung DC subsets in respect to TGF-ß in PF. First, we established BIPF model in mice and blocked TGF-ß expression by the use of inhibitor SB431542. Accumulation of lung CD11c+ DCs is significantly higher in both inflammatory and fibrotic phases of the disease but that percentages got reduced in the absence of TGF-ß. TGF-ß initiates up-regulation of costimulatory molecules CD86 and CD80 in the inflammatory phases of the disease but not so at fibrotic stage. Expression of lung DC subset CD11c+CD103+ is significantly increased in inflammatory phase and also in fibrotic phase of BIPF. Blocking of TGF-ß causes decreased expression of CD11c+CD103+ DCs. Another important lung DC subset CD11c+CD11b+ expression is suppressed by the absence of TGF-ß after bleomycin administration. CD11c+CD103+ DCs might have anti-inflammatory as well as anti-fibrotic nature in PF. All these data demonstrate differential modulation of CD11c+ lung DCs by TGF-ß in experimental PF.

Comorbidity in patients with Dhat syndrome: a nationwide multicentric study.

INTRODUCTION: There are limited numbers of studies on Dhat syndrome. Major limitations of the existing literature are heterogeneous assessment methods used to describe the comorbidity and small sample size from isolated centers. AIM: To assess comorbidity with a common methodology in patients with Dhat syndrome from multiple centers across India. METHODS: Using a cross-sectional design, this multicentric study involved assessment of 780 male patients, aged more than 16 years, across 15 study centers. MAIN OUTCOME MEASURES: ICD-10 criteria (for evaluation of psychiatric morbidity and sexual dysfunction) RESULTS: About one-third (32.8%) of the cases had no comorbidity. One-fifth (20.5%) of the patients had comorbid depressive disorders and another one-fifth (20.5%) had comorbid neurotic, stress-related and somatoform disorders. Half (51.3%) of the study sample had comorbid sexual dysfunction. When various combinations of comorbidities were evaluated, it was seen that more than one-fourth (28.7%) of the patients had only comorbid sexual dysfunction and one-sixth (15.9%) had only comorbid depressive/anxiety disorders. A little more than one-fifth (22.6%) had comorbidity of both sexual dysfunction and depressive/anxiety disorders. CONCLUSION: Comorbid sexual dysfunction is seen in half of the cases of Dhat syndrome, and it is more common than comorbid depressive and anxiety disorders.

Impact of occupational cadmium exposure on spirometry, sputum leukocyte count, and lung cell DNA damage among Indian goldsmiths.

BACKGROUND: Cadmium is frequently used in manual jewelry industries. Although its toxicity on lung function is well-known, the mechanism is not well-understood. METHODS: Among 26 goldsmiths exposed to cadmium (mean age 35.9 ± 5.0 years) and 17 referent workers without direct exposure (36.6 ± 6.6 years), we measured blood and urinary cadmium concentration and performed spirometry and quantified leukocytes and comet formation in the cells from spontaneously expectorated sputum samples. RESULTS: The goldsmiths had higher cadmium concentration in urine (mean 6.14 ± 1.63 vs. 0.47 ± 0.17 µg/dl) and blood (0.90 ± 0.23 vs. 0.02 ± 0.007 µg/dl) than the referents, which were inversely associated with FEV1 /FVC. Cadmium exposure also resulted in higher neutrophils (%) and lower macrophage (%) prevalence in the sputum and also caused substantial DNA damage in the lung cells among the goldsmiths than the referents (69 vs. 14%). CONCLUSION: Altered lung function among cadmium-exposed goldsmiths was associated with enhanced inflammatory response and increased cellular DNA damage in the lungs.

Carboxylated acyclonucleosides: synthesis and RNase A inhibition.

Strategically designed carboxylated acyclonucleosides have been probed as a new class of RNase A inhibitors. Several experimental and theoretical studies have been performed to compile relevant qualitative and quantitative information regarding the nature and extent of inhibition. The inhibition constant (Ki) values were determined using a UV-based kinetics experiment. The changes in the secondary structure of the enzyme upon binding with the inhibitors were obtained from circular dichroism studies. The binding constants for enzyme-inhibitor interactions were determined with the help of fluorescence spectroscopy. Docking studies were performed to reveal the possible binding sites of the inhibitors within the enzyme. The cytosine analogues were found to possess better inhibitory properties in comparison to the corresponding uracil derivatives. An increment in the number of carboxylic acid groups (-COOH) in the inhibitor backbone was found to result in better inhibition.

Wilson disease-causing mutations in the carboxyl terminus of ATP7B regulates its localization and Golgi exit selectively in the unpolarized cells.

Mutational inactivation of the P-type Cu-ATPase ATP7B interferes with its cellular functions to varying extent leading to varied cellular phenotypes. Wilson's disease (WD) primarily affects organs composed of polarized/differentiated epithelial cells. Therefore, phenotypic variability might differ depending on the polarization/differentiation of the cells. The present study investigates the intracellular stability and localization of ATP7B harboring WD mutations in both unpolarized/undifferentiated and polarized/differentiated cell-based models. Green fluorescent protein (GFP)-ATP7B harboring the WD causing mutations, N41S, S653Y, R778Q, G1061E, H1069Q, S1423N, S1426I, and T1434M, are included for investigation. The C-terminal WD mutations (S1423N, S1426I, and T1434M), exhibit distinct localization and Cu(I) responsive anterograde and retrograde trafficking in undifferentiated/unpolarized vs. differentiated/polarized cells. While basal localization of the S1423N mutant gets corrected in the differentiated glia, its Cu(I) responsive anterograde and retrograde trafficking behavior is not identical to the wild-type. But localization and trafficking properties are completely rescued for the S1426I and T1434M mutants in the differentiated cells. Comprehensive meta-analysis on the effect of the reported C-terminal mutations on patient phenotype and cultured cells demonstrate discrete regions having distinct effects. While mutations in the proximal C-terminus affect ATP7B stability, the present study shows that the distal region dictates cell-specific Trans Golgi Network (TGN) localization and exit. The localization and export properties are corrected in the differentiated cells, which is a plausible mechanism for the milder phenotype exhibited by these mutations. It highlights the critical role of the C-terminus in cell-specific TGN retention and exit of ATP7B.

Disability and its correlates among persons with bipolar disorder: Exploratory findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Aim: This study aimed to evaluate the disability and its correlates in persons with Bipolar Disorder during the remission phase. Materials and Methods: As part of the multicentric study, 773 patients with bipolar disorder, currently in clinical remission, were evaluated for disability on the Indian Disability Assessment Evaluation Scale. Results: About one-fifth of the participants had some level of disability in the domain of self-care, one-third had some level of disability in the interpersonal domain, one-fourth had some level of disability in communication and understanding, and a maximum proportion (43.7%) had some disability in the domain of work. Overall, about one-fifth (18.4%) were considered to have a benchmark disability (i.e., disability >40%). In terms of correlates, those with a disability had a short duration of current remission, a higher number of manic and mixed episodes, a higher mean number of total episodes, spent more time in the episodes, had lower severity of the depressive episodes, higher residual depressive and manic symptoms, had overall higher manic affective morbidity, had a higher level of cognitive deficits, and had poorer insight. Conclusion: A significant proportion of patients with bipolar disorder have disability in work domain, and the presence of residual symptoms of either polarity are associated with higher level of disability.

Insight in patients with bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Background: There are limited number of studies evaluating insight among patients with bipolar disorder (BD). Aim: This study aimed to examine insight and its correlates in BD using the data from the multicenter BD course and outcome study from India (BiD-CoIN). The additional aim was to evaluate the insight in patients with BD using different scales and understand the correlates of insight. Materials and Methods: 773 BD patients presently in clinical remission were evaluated on the Insight Scale for Affective Disorders (ISAD), insight items of the Hamilton Depression Rating Scale (HDRS), and the Young Mania Rating Scale (YMRS). Results: The assessment scales influenced the prevalence of poor insight. Poorer insight irrespective of the assessment scale was consistently associated with higher residual depressive and manic symptoms, and a higher level of cognitive impairment and disability. Poor insight as assessed by ISAD was associated with a higher number of episodes in the lifetime, shorter duration of current remission, a higher number of depressive episodes, a higher amount of time spent in depressive episodes, higher depressive affective morbidity, a higher number of manic episodes, and higher residual depressive and manic symptoms. Conclusion: Poor insight in BD is consistently associated with higher residual depressive and manic symptoms and a higher level of cognitive impairment and disability. However, in terms of course variables, the correlates vary depending on the assessment method.

Subjective cognitive deficits and its correlates among patients with bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Aim: This study aimed to evaluate the prevalence of subjective cognitive complaints and their association with clinical variables, insight, and disability. Methodology: Seven hundred and seventy-three subjects with bipolar disorder (BD), recruited across 14 centers, currently in the euthymic phase were cross-sectionally evaluated on Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA). Results: The mean total COBRA score was 9.79 (SD: 6.99), and 322 (41.7%) of the participants were found to have subjective cognitive complaints when the cut-off of >10 was used. Compared to those without cognitive complaints, those with cognitive complaints more often had depression as the first episode in their lifetime, had a higher prevalence of alcohol dependence, a higher number of depressive episodes (first five years of illness, lifetime, and per year of illness), a higher number of manic episodes in the first five years of illness, more often had depressive or indeterminate predominant polarity, lower prevalence of at least one-lifetime episode with psychotic symptoms, higher severity of residual symptoms, spent more time in the episodes in the lifetime, had poorer insight and higher disability. Conclusion: The present study suggests subjective complaints complaints are associated with more severe illness, higher levels of residual symptoms, poor insight, and higher disability.

Copper dependent ERK1/2 phosphorylation is essential for the viability of neurons and not glia.

Intracellular copper [Cu(I)] has been hypothesized to play role in the differentiation of the neurons. This necessitates understanding the role of Cu(I) not only in the neurons but also in the glia considering their anatomical proximity, contribution towards ion homeostasis, and neurodegeneration. In this study, we did a systematic investigation of the changes in the cellular copper homeostasis during neuronal and glial differentiation and the pathways triggered by them. Our study demonstrates increased mRNA for the plasma membrane copper transporter CTR1 leading to increased Cu(I) during the neuronal (PC-12) differentiation. ATP7A is retained in the trans-Golgi network (TGN) despite high Cu(I) demonstrating its utilization towards the neuronal differentiation. Intracellular copper triggers pathways essential for neurite generation and ERK1/2 activation during the neuronal differentiation. ERK1/2 activation also accompanies the differentiation of the foetal brain derived neuronal progenitor cells. The study demonstrates that ERK1/2 phosphorylation is essential for the viability of the neurons. In contrast, differentiated C-6 (glia) cells contain low intracellular copper and significant downregulation of the ERK1/2 phosphorylation demonstrating that ERK1/2 activation does not regulate the viability of the glia. But ATP7A shows vesicular localization despite low copper in the glia. In addition to the TGN, ATP7A localizes into RAB11 positive recycling endosomes in the glial neurites. Our study demonstrates the role of copper dependent ERK1/2 phosphorylation in the neuronal viability. Whereas glial differentiation largely involves sequestration of Cu(I) into the endosomes potentially (i) for ready release and (ii) rendering cytosolic copper unavailable for pathways like the ERK1/2 activation.

Prevalence of psychotic symptoms and their impact on course and outcome of patients with bipolar disorder: Findings from the Bipolar Disorder Course and Outcome study from India (BiD-CoIN study).

AIM: Most of the available data on the prevalence and impact of psychotic symptoms on the course of bipolar disorder (BD) is from Western countries. We aimed to study the prevalence of at least one psychotic episode in the lifetime in patients with BD and its association with the long-term course and outcome. METHODOLOGY: 773 patients recruited as part of the Bipolar Disorder Course and Outcome study from India (BiD-CoIN study) were divided into 2 groups, based on the presence or absence of at least one psychotic episode in the lifetime. RESULTS: 326 (42.2%) patients had at least one psychotic episode in their lifetime. At least one psychotic episode in the lifetime was associated with overall more severe illness in terms of lower age of onset, a higher number of episodes in the first 5 years of illness; higher rates of BD-II, a higher rate of lifetime history of at least 1 suicide attempt, lifetime history of hospitalization, history of receiving Electroconvulsive Therapy, and a higher prescription rates of antipsychotics. However, presence of psychotics symptoms was associated with better cognitive functioning. CONCLUSIONS: Our findings suggest that the presence of psychotic symptoms during episodes in patients with BD is associated with poorer course of BD.

Prevalence and association of comorbid substance dependence on the course and outcome of bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Aim: To evaluate the prevalence of substance use disorder (SUD) and its association with the course and outcome of bipolar disorder (BD). Materials and Methods: A total of 773 patients with BD were recruited from 14 centers in different parts of India, and they were evaluated for the prevalence of comorbid substance dependence, course and outcome, subjective cognitive functioning, and disability. Results: About one-fourth (22.9%) of the participants had one or more substance dependence. In terms of specific substance of abuse, 136 (17.6%) had nicotine dependence, 80 (10.3%) patients had alcohol dependence, 13 (1.7%) had cannabis dependence, and nine (1.2%) had opioid dependence. Compared to those without comorbid substance dependence, those with a dual diagnosis (i.e., using at least one substance in a dependent pattern) were less educated, more often males, more often currently single, more often employed, had a lower number of depressive episodes per year of illness, had a higher number of manic and mixed episodes per year of illness in the first 5 years of illness, had a higher level of disability, and more often had a history of hospitalization and a history of receiving electroconvulsive therapy (ECT); also, a higher proportion of them had manic predominant polarity, more often had recurrent mania course, and were more often receiving a combination of lithium and valproate. Conclusion: About one-fourth of BD patients have comorbid SUDs, and presence of SUD has a negative impact on the course and outcome of BD.

Club drugs: review of the 'rave' with a note of concern for the Indian scenario.

'Club drugs' which include Ecstasy, gamma-hydroxybutyrate (GHB), ketamine, and Rohypnol (flunitrazepam) have become popular with participants in 'raves', because they are perceived to enhance energy, endurance, sociability and sexual arousal. These drugs vary in their pharmacologic properties, physiological and psychological effects, and potential consequences. The use of club drugs by young people has increased in the last decade, and continue to get modified and evolve, making them very difficult to monitor. Further, these drugs are not picked up by routine drugs screening procedures, thereby making these popular with the criminals. India, which is in a phase of social transition, also faces this rising menace. Despite the nature and extent of this problem, this area has been under-researched. Data from India are sparse barring a few newspaper and police reports. Keeping abreast of current trends in club drug use prepares the clinician to recognize the clinical effects of club drug use, to manage club drug related emergencies, and to generate social awareness.

Prevalence & correlates of metabolic syndrome in alcohol & opioid dependent inpatients.

BACKGROUND & OBJECTIVES: The research on the association of metabolic syndrome (MS) and substance abuse is scanty. The present research aimed to study the prevalence and correlates of MS among the inpatients at a Drug De-addiction Centre in north India. METHODS: Consecutive male subjects (N=110) admitted to a drug de-addiction centre during July to December 2009 with a primary diagnosis of alcohol or opioid dependence were evaluated for the presence of MS as per the International Diabetes Federation (IDF) criteria. RESULTS: The prevalence of MS was 24.6 and 29.3 per cent in alcohol and opioid dependent groups, respectively. MS showed a significant association with the age and body mass index (BMI) in the opioid dependent group. Co-morbid tobacco use was not associated with MS in either group. INTERPRETATION & CONCLUSIONS: The prevalence of MS in our sample of alcohol and opioid dependent male inpatients was greater than the prevalence of MS in general population, however it was comparable to that reported in physical and other psychiatric disorder populations. Even though the absence of any comparative study limits the generalizability of our findings, results indicate towards a need for screening of the patients with substance dependence especially for those aged above 30 years and/or having a high BMI for MS.

Genes regulating development and behavior exhibited altered expression in Drosophila melanogaster exposed to bisphenol A: use of real-time quantitative PCR (qRT-PCR) and droplet digital PCR (ddPCR) in genotoxicity study.

Toxicity of bisphenol A on morphological and life-history traits of model insect Drosophila melanogaster was reported in our previous work. In the present study, we have analyzed the adversity of bisphenol A on the reproductive behavior of adult and on the expression of selected genes in the larva and adult stage of fruit fly exposed to bisphenol A (0.007 g/2 ml. or 3.5 mg/ml), in addition to determination of LC50 value of bisphenol A in larva and pupal stage. We employed both the quantitative reverse transcriptase PCR and droplet digital PCR for analyzing the expression profile of seven genes namely, decapentaplegic, vestigial, wingless, foraging, insulin-like receptor, doublesex, and fruitless. We found bisphenol A has more adverse effects on male sexual behavior than females. Moreover, we observed significant downregulation of all the selected genes in treated larvae except, fruitless in male where it showed significant upregulation. On contrary among the treated adult flies, significant downregulation of all target genes in both sexes is evident, except, doublesex and fruitless in males which showed significant upregulation. We did not observe any deviation of male: female sex ratio from 1:1 under bisphenol A exposure. All these results suggest bisphenol A adversely affects the optimum functioning of genes which are involved in the regulation of metabolic pathways, behavioral pattern, stress response, endocrine homeostasis, neural functioning, and the development of the specific organ in Drosophila melanogaster. Our result not only provides a foundation to study further the bisphenol A toxicity on different pivotal genes in Drosophila but also suggests the use of the droplet digital PCR technology in toxicity measurement at the molecular level in eukaryotic model systems.