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.

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.

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.

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.

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 ¯].

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.

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.

Evaluation of Psychological Impact of COVID-19 on Health-Care Workers.

BACKGROUND: Little information is available from India about the psychological impact of COVID-19 on helath-care workers. AIM: The current study aimed to evaluate the psychological issues among the health-care workers (HCW) during the COVID-19 pandemic. MATERIALS AND METHODS: An online survey using Survey Monkey® platform was carried out to evaluate depression (using Patient Health Questionnaire-9), anxiety (using Generalized Anxiety Disorder Questionnaire-7), and other psychological issues (using a self-designed questionnaire). RESULTS: The study sample comprised 303 participants with a mean age of 41.2 (standard deviation: 11.1) years. A majority of them were male (69%) and married (79.9%). Nearly half (46.2%) of the participants had either anxiety disorder or depression or both and 12.9% of HCW had suicidal behavior. Higher level of anxiety and depression scores were associated with being female, having undergone quarantine, directly involved in the care of COVID-19 patients, and younger age (<30 years). Higher prevalence of depression and anxiety disorder was seen in younger (<30 years) age group, being a doctor (compared to paramedics). In addition, higher prevalence of depression was seen in those who were directly involved in the care of patients with COVID-19 infection. CONCLUSION: About half of the HCWs are suffering from psychiatric morbidity, specifically anxiety, in the wake of the COVID-19 pandemic. There is a need to assess all the HCWs for psychiatric morbidity and provide them with psychological support.

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.

Residual symptoms in bipolar disorders: Findings from the bipolar Disorder course and outcome study from India (BiD-CoIN study).

AIM: To explore the prevalence of residual symptoms (both depressive and manic) and their correlates in subjects with bipolar disorder in clinical remission. METHODOLOGY: This multicentric cross-sectional study included patients in clinical remission recruited across the 14 centers. The patients were evaluated on the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) for the prevalence of residual symptoms. A score of ≤7 on both scales defined the presence of residual symptoms. RESULTS: Four-fifth (79.8%) of the participants had residual symptoms, with 130 (16.8%) having only residual depressive symptoms, 74 (9.6%) having only residual manic symptoms, and 413 (53.4%) having both depressive and manic residual symptoms, on HDRS and YMRS. The residual symptoms were related to the polarity of the most recent episode and the lifetime predominant polarity. Higher numbers of lifetime depressive episodes are associated with higher residual depressive symptoms, and higher numbers of lifetime manic episodes are associated with higher chances of having residual manic symptoms. CONCLUSIONS: A large proportion of patients with bipolar disorder have residual symptoms during the remission phase. Clinicians need to make efforts to identify and address the same to improve the treatment outcome.

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.

Prescription patterns in clinically stable patients with bipolar disorder: Findings from the Bipolar Disorder Course and Outcome from India (BiD-CoIN) study.

AIM: To evaluate the prescription pattern of patients with BD, currently in clinical remission. Additional aim of the study was tocompare the prescription pattern across different study centres. METHODOLOGY: Prescription of 773 patients, currently in clinical remission, recruited from the outpatient setting of 14 General Hospital Tertiary Care Units of tertiary care centres in the country were evaluated. RESULTS: Almost all (98.1 %) participants were on medications at the time of assessment. In terms of conventional mood stabilizers, those receiving valproate (44.2 %), out-numbered those receiving lithium (38.9 %). A small proportion (7.4 %) was receiving a combination of both valproate and lithium. About two-third (62.5 %) were receiving at least one antipsychotic medication, with olanzapine (31.7 %) being the most commonly prescribed antipsychotic, followed by quetiapine (11.1 %), and risperidone (9.6 %). About one-third (34.4 %) of the participants were receiving antidepressants, with sertraline (22.6 %) forming bulk of the prescription. Less than half (43.9 %) of the participants were also receiving a benzodiazepine medication at the time of assessment, with chlordiazepoxide (18 %) being the most common agent, followed by clonazepam (14.5 %). There was variation in the prescription patterns across different centres, in terms of monotherapy, polypharmacy, use of preferred conventional mood stabilizers, use of various antipsychotics and antidepressants. CONCLUSION: Besides conventional mood stabilizers, about two-third of patients with bipolar disorder received concomitant antipsychotics, one-third received concomitant antidepressants and less than half received benzodiazepines.

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.

Bipolar Disorder Course and Outcome Study from India (BiD-CoIN study): Sample Description & Methods.

OBJECTIVES: This multicentric study from India aimed to evaluate the long term course and outcome of bipolar disorder (BD). METHOD: Seven hundred and seventy-three participants diagnosed with BD, attending 14 outpatient clinic centers across the country, were evaluated using the National Institute of Mental Health- Retrospective Life Charts to assess the long term course of BD. RESULTS: The mean age of onset of the first episode of illness of the study sample was 26.3 (8.54) years, and mean duration of illness at the time of assessment was 233.05 (94.55) months. In terms of the total number of lifetime episodes, the mean number of manic episodes (mean: 3.68; SD: 4.75) exceeded the mean number of depressive episodes (mean: 3.36; SD: 5.51). The mean numbers of total lifetime episodes were 8.58 (10.6%). When the number of episodes per year was computed, the mean number of manic episodes per year exceeded that of the mean number of depressive episodes. Compared to females, a higher proportion of males had a history of comorbid substance dependence. LIMITATIONS: The course was assessed retrospectively and the study was limited to participants attending the outpatient clinics. CONCLUSIONS: The course of BD in India differs from that described from developed countries in the form of a number of manic episodes exceeding the depressive episodes.