MAP2 is differentially phosphorylated in schizophrenia, altering its function.

Schizophrenia (Sz) is a highly polygenic disorder, with common, rare, and structural variants each contributing only a small fraction of overall disease risk. Thus, there is a need to identify downstream points of convergence that can be targeted with therapeutics. Reduction of microtubule-associated protein 2 (MAP2) immunoreactivity (MAP2-IR) is present in individuals with Sz, despite no change in MAP2 protein levels. MAP2 is phosphorylated downstream of multiple receptors and kinases identified as Sz risk genes, altering its immunoreactivity and function. Using an unbiased phosphoproteomics approach, we quantified 18 MAP2 phosphopeptides, 9 of which were significantly altered in Sz subjects. Network analysis grouped MAP2 phosphopeptides into three modules, each with a distinct relationship to dendritic spine loss, synaptic protein levels, and clinical function in Sz subjects. We then investigated the most hyperphosphorylated site in Sz, phosphoserine1782 (pS1782). Computational modeling predicted phosphorylation of S1782 reduces binding of MAP2 to microtubules, which was confirmed experimentally. We generated a transgenic mouse containing a phosphomimetic mutation at S1782 (S1782E) and found reductions in basilar dendritic length and complexity along with reduced spine density. Because only a limited number of MAP2 interacting proteins have been previously identified, we combined co-immunoprecipitation with mass spectrometry to characterize the MAP2 interactome in mouse brain. The MAP2 interactome was enriched for proteins involved in protein translation. These associations were shown to be functional as overexpression of wild type and phosphomimetic MAP2 reduced protein synthesis in vitro. Finally, we found that Sz subjects with low MAP2-IR had reductions in the levels of synaptic proteins relative to nonpsychiatric control (NPC) subjects and to Sz subjects with normal and MAP2-IR, and this same pattern was recapitulated in S1782E mice. These findings suggest a new conceptual framework for Sz-that a large proportion of individuals have a "MAP2opathy"-in which MAP function is altered by phosphorylation, leading to impairments of neuronal structure, synaptic protein synthesis, and function.

Prevalence and Predictors of Abuse in Elderly Patients with Depression at a Tertiary Care Centre in Saurashtra, India.

CONTEXT: Elder abuse has devastating consequences such as poor quality of life, psychological distress and loss of property and security. Abuse of elderly patients with depression has not been adequately researched in India. AIMS: To explore the prevalence and predictors of abuse and its relation to various sociodemographic variables in elderly patients with depression. SETTINGS AND DESIGN: A cross-sectional, observational study carried out at a tertiary care centre in Jamnagar. METHODS AND MATERIALS: In all, 100 elderly patients with depression, attending Out Patient Department of Psychiatry at Shree M. P. Shah Government Medical College and Guru Gobind Singh Hospital, Jamnagar, were selected using simple random sampling by lottery method. Actual Abuse Tool and Elder Abuse Suspicion Index were used to detect abuse. Geriatric Depression Scale was used to assess depression, and Mini Mental State Examination was used to rule out dementia. STATISTICAL ANALYSIS: Descriptive statistics, Chi-square test, and binary logistic regression were used. RESULTS: The prevalence of abuse was 24%. Among those who had experienced abuse, 50% had experienced psychological abuse, 17% had experienced neglect, 8% had experienced exploitation and 4% had experienced physical abuse. About 54% of patients with severe depression had experienced abuse. Daughters-in-law (54%) and sons (42%) were the most common perpetrators. Illiteracy and severe depression were found to be the predictors of abuse.

Liquisolid Tablets for Dissolution Enhancement of a Hypolipidemic Drug.

This investigation was aimed to improve the dissolution rate of the poorly soluble drug lovastatin, by formulating it as a liquisolid compact. Different liquisolid compacts were prepared using mathematical formulae to calculate the required quantities of powder and liquid ingredients to produce acceptably flowable and compressible admixture. Avicel PH 200, Cab-O-Sil, sodium starch glycolate and PEG 400 were employed as carrier, coating material, disintegrant and non-volatile liquid vehicle, respectively. The various drug to liquid and carrier to coating ratio were used to prepare liquisolid compacts. The formulated liquisolid tablets were evaluated for weight variation, hardness, drug content, friability and disintegration time. The in vitro release characteristics of the drug from tablets formulated by direct compression and liquisolid technique were compared in two different dissolution media. The tableting properties of the liquisolid compacts were within the acceptable limits and drug release rates were distinctly higher as compared to directly compressed tablets. The FTIR spectra showed no interaction between drug-excipient and disappearance of the characteristic absorption band of lovastatin in liquisolid formulations could be attributed to the formation of hydrogen bonding between the drug and liquid vehicle, which resulted in dissolution enhancement. Thus, the liquisolid technique was found to be a promising approach for improving the dissolution of a poorly soluble drug like lovastatin.

Work of breathing during SIMV with and without pressure support.

OBJECTIVE: In a randomised trial, pressure support with synchronised intermittent mandatory ventilation (SIMV) compared to SIMV alone was associated with a significant reduction in supplementary oxygen duration. The hypothesis that the addition of pressure support to SIMV compared to SIMV alone would reduce the work of breathing was examined. DESIGN: Prospective study. SETTING: Perinatal service. PATIENTS: 20 infants, with a mean gestational age of 31 weeks, being weaned from mechanical ventilation were studied. INTERVENTIONS: 1 h periods of SIMV and SIMV with pressure support at 50% of the difference between the peak inflating pressure and positive end expiratory pressures. MAIN OUTCOME MEASURES: The work of breathing was assessed by measurement of the transdiaphragmatic pressure time product (PTPdi). RESULTS: The mean PTPdi on SIMV plus pressure support was 112 cm H(2)Oxs/min, approximately 20% lower than that on SIMV alone (141 cm H(2)Oxs/min) (p<0.001). CONCLUSION: The addition of pressure support to SIMV reduces the work of breathing in infants being weaned from the ventilator.

Modeling and informatics in designing anti-diabetic agents.

Diabetes mellitus is a chronic metabolic disorder, characterized by glucose overproduction and glucose underutilization. Current therapy for T2DM includes drugs, like metformin, glitazones, sulphonyl ureas, etc. Extensive research has been carried out world wide on molecular targets for T2DM like PPARgamma, PTP1B, DPP-IV, GSK-3, cannabinoid receptor, fructose-bisphosphatases, beta3 adrenoceptor, etc. in the development of newer anti-diabetic agents. These therapeutic targets are quite important and most of them are suitable for in silico analysis. Hence, many molecular modeling and informatics studies like, molecular docking, pharmacophore mapping, 3D-QSAR, virtual screening, quantum chemical studies, and pharmacoinformatics like bioinformatics and chemoinformatics studies have been performed on the drugs/leads/targets associated with T2DM. Several of these in silico efforts are exemplary studies; the methodologies adopted in these studies can be emulated in many other therapeutic areas. A review of the rational approaches reported in designing anti-diabetic agents is presented in this article.

Understanding barriers to preventive health actions for occupational noise-induced hearing loss.

A theoretically based formative evaluation was conducted with coal miners in the Appalachian Mountains who were at high risk for noise-induced hearing loss (NIHL). The results of four focus groups indicate that despite high levels of knowledge, strong perceived severity of negative consequences, and strong perceived susceptibility to hearing loss, two main categories of barriers (environmental and individual) keep coal miners from using their hearing protection devices (HPD). Further analysis suggests that the environmental factors, rather than individual variables, more strongly influence decisions against protective actions. Recommendations and practical implications are offered.

Treatment of atrophoderma of Pasini and Pierini-associated hyperpigmentation with the Q-switched alexandrite laser: a clinical, histologic, and ultrastructural appraisal.

BACKGROUND AND OBJECTIVE: Atrophoderma of Pasini and Pierini (APP) is an uncommon cutaneous disorder, with no known effective treatment, manifested by hyperpigmented patches that appear to be depressed compared with surrounding skin. This study investigated the effectiveness of the Q-switched alexandrite laser on a patient with extensive APP, and evaluated histopathologic and ultrastructural changes. STUDY DESIGN/MATERIALS AND METHODS: A man with stable APP underwent Q-switched alexandrite laser treatment to a patch on the trunk. Biopsies were obtained from treated and untreated sites of involvement. Light and transmission electron microscopic evaluation was performed to investigate melanosome number, size, and volume, as well as melanin granule number and size. RESULTS: After three treatment sessions, the treated area showed marked clinical improvement. Electron microscopy showed a 19% reduction in melanin granule number and size and a 65% reduction in melanosome number, size, and volume in larger melanosomes in treated compared with untreated sites. CONCLUSION: Treatment of APP with the Q-switched alexandrite laser results in clinical improvement. Electron microscopic evaluation suggests that the mechanism may be a reduction in the number, size, and volume of larger melanosomes as well as a decrement in melanin granule number and size.

Pulsed-dye laser versus conventional therapy in the treatment of warts: a prospective randomized trial.

BACKGROUND: The clinical management of verrucae vulgaris is often challenging, and no ideal treatment currently exists. Early studies suggested that pulsed-dye laser (PDL) therapy might be highly effective in the treatment of verrucae, although more recent reports have been less optimistic. Previous studies have been retrospective or have consisted of a series of patients treated with PDL alone. OBJECTIVE: Our objective was to prospectively evaluate the efficacy of PDL therapy versus conventional therapy with liquid nitrogen cryotherapy or cantharidin in the treatment of warts. METHODS: Forty healthy adult patients with verrucae were randomized to receive either PDL (585 nm) therapy or conventional therapy. All enrollees also performed home therapy. Patients were eligible for up to 4 treatment sessions at 1-month intervals. Warts were individually counted and measured at the time of each treatment session. Complete response was defined as complete absence of verrucae with the presence of dermatoglyphics, and partial response was defined as a 50% or greater reduction in wart size. RESULTS: A total of 194 warts were evaluated by the conclusion of the study. Complete response was noted in an average of 70% of the warts treated with conventional therapy and in 66% of those in the PDL group; this was statistically insignificant. Partial response was observed in an average of 82% of the warts in patients treated with conventional therapy and 87% in the PDL group. Verruca vulgaris responded more readily than verruca plantaris in both treatment groups. The mean number of treatments to achieve success was similar in both groups. CONCLUSION: The PDL is an efficacious form of therapy for verrucae, as is conventional therapy. PDL therapy should be considered among the better established approaches in the treatment of warts, although data from this trial suggest that this approach is probably not superior.

Biodegradation of dimethylterephthalate by Comamonas acidovorans D-4.

Comamonas acidovorans D-4, capable of utilizing dimethylterephthalate (DMT) as the sole carbon source, was isolated from the activated sludge of petrochemical wastewater treatment plant. Almost complete utilization of as high as 0.5% (w/v) DMT was observed in 72 hr. Growth kinetics followed a parallel relation between the growth, DMT utilization and cell associated esterase activity. A cell free broth of DMT grown cells showed an extracellular esterase activity. During the DMT degradation an extracellular accumulation of terephthalic acid was found. Although, C. acidovorans grew on a number of phthalate esters and phthalic acids as the sole carbon source, growth was significantly high on phthalic acids. The potential of this organism in petrochemical pollution abatement is discussed.

Blue nevus of the uterine cervix.

The clinical, gross pathologic, and light and electron microscopic features of three blue nevi of the endocervix were studied. Immunocytochemical studies for the localization of S-100 protein in the blue nevus cells were performed. A comprehensive review of 47 previously published cases is also presented. Blue nevi of the endocervix appear to be rare incidental lesions; they are often found in hysterectomy specimens from middle-aged women. The lesion is seldom detected clinically or colposcopically. However, it appears in most instances as a blue-black lesion in the posterior wall of the endocervix on gross pathologic examination. The demonstration of S-100 protein in the blue nevus cells before and after bleaching in the present study, along with the ultrastructural observations, supports combined melanocytic and schwannian differentiation of the blue nevus cell.