Perventricular device closure of muscular ventricular septal defects on the beating heart

This report describes our initial experience with intraoperative device closure of muscular ventricular septal defects under echocardiographic guidance without cardiopulmonary bypass in two patients.     

The matricellular protein CCN3 regulates NOTCH1 signalling in chronic myeloid leukaemia

Deregulated NOTCH1 has been reported in lymphoid leukaemia, although its role in chronic myeloid leukaemia (CML) is not well established. We previously reported BCR‐ABL down‐regulation of a novel haematopoietic regulator, CCN3, in CML; CCN3 is a non‐canonical NOTCH1 ligand. This study characterizes the NOTCH1–CCN3 signalling axis in CML. In K562 cells, BCR‐ABL silencing reduced full‐length NOTCH1 (NOTCH1‐FL) and inhibited the cleavage of NOTCH1 intracellular domain (NOTCH1‐ICD), resulting in decreased expression of the NOTCH1 targets c‐MYC and HES1. K562 cells stably overexpressing CCN3 (K562/CCN3) or treated with recombinant CCN3 (rCCN3) showed a significant reduction in NOTCH1 signalling (> 50% reduction in NOTCH1‐ICD, p < 0.05). Gamma secretase inhibitor (GSI), which blocks NOTCH1 signalling, reduced K562/CCN3 colony formation but increased that of K562/control cells. GSI combined with either rCCN3 or imatinib reduced K562 colony formation with enhanced reduction of NOTCH1 signalling observed with combination treatments. We demonstrate an oncogenic role for NOTCH1 in CML and suggest that BCR‐ABL disruption of NOTCH1–CCN3 signalling contributes to the pathogenesis of CML. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

First controlled treatment trial of bipolar II hypomania with mixed symptoms: Quetiapine versus placebo

Objectives

To compare the efficacy and safety of adjunctive quetiapine (QTP) versus placebo (PBO) for patients with bipolar II disorder (BDII) currently experiencing mixed hypomanic symptoms in a 2-site, randomized, placebo-controlled, double-blind, 8-week investigation.

Methods

Participants included 55 adults (age 18–65 years) who met criteria for BDII on the Structured Clinical Interview for DSM-IV-TR (SCID). Entrance criteria included a stable medication regimen for ≥2 weeks and hypomania with mixed symptoms (>12 on the Young Mania Rating Scale [YMRS] and >15 on the Montgomery Asberg Depression Rating Scale [MADRS] at two consecutive visits 1–3 days apart). Participants were randomly assigned to receive adjunctive quetiapine (n=30) or placebo (n=25).

Results

Adjunctive quetiapine demonstrated significantly greater improvement than placebo in Clinical Global Impression for Bipolar Disorder Overall Severity scores (F(1)=10.12, p=.002) and MADRS scores (F(1)=6.93, p=.0138), but no significant differences were observed for YMRS scores (F(1)=3.68, p=.069). Side effects of quetiapine were consistent with those observed in previous clinical trials, with sedation/somnolence being the most common, occurring in 53.3% with QTP and 20.0% with PBO.

Conclusions

While QTP was significantly more effective than PBO for overall and depressive symptoms of BDII, there was no significant difference between groups in reducing symptoms of hypomania. Hypomania improved across both groups throughout the study.     

The Alarm Response in Zebrafish: Innate Fear in a Vertebrate Genetic Model

The alarm response is an antipredator behavior displayed by many fish species and was first described 70 years ago. It is triggered through the olfactory system by substances released from injured skin and is characterized by dramatic, measurable changes in locomotion as well as physiology. We propose that this is an ideal time to revisit this response and to utilize it as an assay for understanding how neural circuits mediate innate fear. A suitable organism for these studies is the zebrafish, a genetic model with a rapidly expanding toolkit for molecular manipulation of the nervous system. Individual neurons mediating the response, ranging from receptor neurons to those in higher brain centers, should first be identified. New tools, specifically transgenic lines that allow spatial and temporal control of neural activity, provide a way to define and test the role of specific neurons, while genetic screens provide a route to identifying individual molecules essential for a normal response. Optical recording, which has proven successful in studies of information processing in the bulb, will provide valuable insights into neural circuitry function during the alarm response. When carried out on mutants, physiological analysis can provide insight into aspects of signal processing that are essential for normal behavior. The alarm response thus provides a paradigm to examine innate fear in a vertebrate system, enabling analysis at multiple levels from genes to the entire neural circuit. Additionally, the context dependency of the response can be utilized to investigate attention and decision making.     

Embracing Technology for Capacity Building in Mental Health: New Path,Newer Challenges

Psychiatric Quarterly - Technology driven capacity building initiatives are the way to break the barrier of shortage of mental health human resources in India. This new path, while is a welcome...     

Development of aceclofenac nanovesicular system using biomaterial for transdermal delivery: physical characterization,ex vivo,in vivo,and anti-inflammatory studies

Context: Aceclofenac is an important NSAID; however, it causes GI disturbances whereas employing transdermal route would require permeation enhancer for systemic application, thereby causing skin damage. Ceramide 2 is a natural lipid having an important role in the maintenance of skin. Objective: Aceclofenac-loaded nanovesicles of ceramide-2, cholesterol, palmitic acid, and cholesteryl sulfate were formulated and analyzed for physical and biological properties. Materials and method: Film hydration method was used to prepare the vesicles and physical parameters, in vitro drug release and stability were evaluated. Then, they were formulated into gel and evaluated against a commercial formulation (CF) and gel-containing plain drug (CPG) for ex vivo, in vivo drug permeation, and anti-inflammatory activity. Results: The developed formulations showed best physical profile and ACV-1 gave 92.89% drug release in in vitro studies. Ex vivo studies showed drug permeation between 15.32–31.12?μg/cm², whereas CPG and CF released 0.47 and 2.81?μg/cm², respectively. ACVG-1 and CF showed C_max of 8.1 and 1.2?μg/ml at 8 and 4?h, respectively. ACVG-1 showed 11.6 times AUC than CF. ACVG-1 inhibited edema by 44% in first hour itself. Discussion: Ceramide 2 and palmitic acid played an important role in the formulation and promotes the drug permeation through stratum corneum and dermis. Ceramide content of the formulation also contributes towards stability and skin protection. Conclusion: The composition of the vesicle formulation performs an important role in physical properties and drug permeation, thereby producing an optimum formulation.     

Prevalence of malnutrition in a tertiary care hospital in India

Introduction:

Malnutrition adversely affects clinical outcome of hospitalized patients. This observational prospective study was done to assess the prevalence of malnutrition and its grade among patients admitted in a mixed intensive care unit (ICU) of a tertiary care hospital in order to help devise a comprehensive nutrition program for the malnourished.

Materials and Methods:

A total of 500 sequential patients admitted to the ICU were screened on admission over a year period for malnutrition using the Subjective Global Nutritional Assessment (SGNA) score. Distribution of the degree of malnutrition according to co-morbidities was also documented.

Results:

Of the total, 198 (39.6%) patients were malnourished, including one patient qualifying as severely malnourished; 68% patients were male, however, there was no statistically significant difference between nutrition status between sexes. Hypertension, diabetes, and cancer were the three most commonly encountered co-morbidities among the malnourished. A total of 86% of all cancer patients admitted were malnourished against only 12% of trauma patients.

Conclusion:

This study showed that almost two-fifth of the patients admitted were malnourished in this tertiary care hospital and that there is an urgent need to develop a comprehensive nutritional care program in many such Indian ICUs.