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.

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.

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.

Depression, Sexual Dysfunction, and Medical Comorbidities in Young Adults Having Nicotine Dependence.

BACKGROUND: Nicotine dependence, depression, diabetes mellitus, hypertension, and hypothyroidism are risk factors of sexual dysfunction. AIMS AND OBJECTIVES: The present study aims to find the prevalence of sexual dysfunction and the various sexual response cycle domains in individuals with nicotine dependence with and without comorbidities. MATERIALS AND METHODS: A total of 52 individuals attending the tobacco cessation clinic were included in the study. To assess the primary outcome, Fagerstrom test for nicotine dependence, Arizona Sexual Experiences Scale, and Hamilton's Depression Rating Scale 17had been administered after validation in local vernacular. RESULTS: In the sample, 32 (61.5%) were male and 20 (38.5) were female. The 17 participants (32.7%) met the criteria of low nicotine dependence, 5 (9.6%) participants met low to moderate, 11 participants (21.2%) had moderate dependence, and 19 (36.5%) participants met the criteria of high nicotine dependence. CONCLUSIONS: The nicotine dependence is directly related to sexual dysfunction, and it affects various stages of the sexual response cycle. One-quarter of individuals of nicotine dependence also met the threshold criteria of depression. The interventions as primary and primordial preventions with awareness building and health education may be a cost-effective measure to prevent tobacco-related deaths.

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.

Cellular copper homeostasis: current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases.

Copper is a trace element essential for almost all living organisms. But the level of intracellular copper needs to be tightly regulated. Dysregulation of cellular copper homeostasis leading to various diseases demonstrates the importance of this tight regulation. Copper homeostasis is regulated not only within the cell but also within individual intracellular compartments. Inactivation of export machinery results in excess copper being redistributed into various intracellular organelles. Recent evidence suggests the involvement of glutathione in playing an important role in regulating copper entry and intracellular copper homeostasis. Therefore interplay of both homeostases might play an important role within the cell. Similar to copper, glutathione balance is tightly regulated within individual cellular compartments. This review explores the existing literature on the role of glutathione in regulating cellular copper homeostasis. On the one hand, interplay of glutathione and copper homeostasis performs an important role in normal physiological processes, for example neuronal differentiation. On the other hand, perturbation of the interplay might play a key role in the pathogenesis of copper homeostasis disorders.

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.

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.

Modulation of phenotypic and functional maturation of murine bone-marrow-derived dendritic cells (BMDCs) induced by cadmium chloride.

Cadmium (Cd(2+)) has been classified as a type I human carcinogen by the International Agency for Research on Cancer. In the present study, we are going to report for the first time on the detailed modulation of phenotypic and functional maturation of murine bone marrow-derived dendritic cells (BMDCs) induced by cadmium chloride. Dendritic cells (DCs) are major modulators in the whole immune system. One dynamic field of research is the manipulation of DCs as pharmacological targets to screen novel biological modifiers for the treatment of tumor, inflammatory and autoimmune disorders. Phenotypic and functional maturation of BMDCs was evaluated by phase-contrast light microscope for primary cultures, flow cytometry (FCM) for important DC markers, reverse-transcriptase PCR and enzyme linked immunosorbent assay (ELISA) for cytokines. Cd(2+)-induced BMDC death was also performed by comet assay. Our results elucidated that Cd(2+) suppressed maturation of BMDCs via changes as reflected by the decreased expression of key surface molecules such as MHCII and CD40, and also by releasing the lower level of IL-12p70. The change of expression of other co-stimulatory molecules such as CD86 and CD80 was not so significant. However, it was found that cadmium promotes releasing a higher level of IL-23 from BMDCs. So from our study, it can be concluded that cadmium may be one of the potent immunosuppressive agents through the blockage of DC maturation and function.

Erectile dysfunction in patients with diabetes mellitus: its magnitude, predictors and their bio-psycho-social interaction: a study from a developing country.

BACKGROUND: Persons suffering from diabetes mellitus (DM) are at higher risk of developing erectile dysfunction (ED). Several factors contribute to ED in patients of DM. Only few studies have attempted to explore physical, psychological and social factors in a single study. The aim of the index study was to measure the prevalence of ED in patients of DM and to determine the contributory role of various socio-demographic, physical, and psychological variables. METHOD: One hundred and thirteen (N = 113) consenting consecutive male married diabetic patients were assessed on International Index of Erectile Function Questionnaire (IIEFQ-5), Dyadic Adjustment Scale (DAS) and Beck's Depression Inventory (BDI) to measure erectile performance, quality of marriage and depressive symptoms respectively. Pretested Bengali versions of these scales were used in the index study. RESULTS: Prevalence of ED was 38.94%. ED group significantly differed from non-ED group in current age, family type, type of treatment for diabetes, presence of micro/macrovascular complications, history of current tobacco use, quality of marriage, and presence of depressive symptoms. In logistic regression analysis current age, body mass index (BMI) and presence of depressive symptoms had significant predictive role on occurrence of erectile dysfunction. CONCLUSION: Prevalence of ED among diabetic patients is high compared to general population. Both physical and psychosocial factors predict the occurrence of ED in this group. So, both physicians and psychiatrists should remain aware about the multi-faceted causative role of ED in DM.

Pattern of psychotropic prescription in a tertiary care center: a critical analysis.

OBJECTIVES: To study the prescription pattern of psychotropic drugs in a Tertiary Care Hospital in Eastern India with special reference to polypharmacy. MATERIALS AND METHODS: A total of 411 patients were included in the study through systematic sampling. Patients were diagnosed by a Consultant Psychiatrist before inclusion in the study using a semi-structured interview schedule based on the International Classification of Disease (ICD), classification of mental and behavioral disorders, 10th version). The most recently prescribed psychopharmacological medication of those patients was studied. A checklist to assess the pattern of prescription and evaluate reasons of polypharmacy was filled up by the prescribing consultant. RESULTS: About 76.6% of the patients received polypharmacy in the index study. Males were more exposed to polypharmacy compared to women (80.93% vs. 70.85%). Gender and diagnosis had a predictive value with regard to the polypharmacy. Polypharmacy was more common in organic mental disorders (F0), psychoactive substance abuse disorders (F1), psychotic disorders (F2), mood disorders (F3) and in childhood, and adolescent mental disorders (F9). Most frequently, antipsychotic drugs were prescribed followed by tranquilizers/hypnotics and anticholinergics. Antidepressants (35.13%) were more commonly prescribed as monotherapy. Anticholinergics (100%) and tranquilizers/hypnotics (96.7%) were the drugs more commonly used in combination with other psychotropics. The three most common reasons for prescribing polypharmacy were augmentation (43.8%) of primary drug followed by its use to prevent adverse effects of primary drug (39.6%) and to treat comorbidity (34.9%). CONCLUSIONS: Polypharmacy is a common practice despite the research based guidelines suggest otherwise. More vigorous research is needed to address this sensitive issue.

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.