Clinical and biochemical parameters in relation to serum leptin levels in South Indian children and adolescents

Objective  

To investigate the relationship between serum leptin and lipid profile in South Indian School children and adolescents, and to evaluate the role of serum leptin in obese, overweight and congenital heart diseased children and adolescents; in South Indian population and its correlation with anthropometric and biochemical parameters.     

Ovarian cancer targeted adenoviral-mediated mda-7/IL-24 gene therapy

OBJECTIVE: We have previously shown that adenoviral-mediated melanoma differentiation-associated gene-7 (Ad.mda-7) therapy induces apoptosis in ovarian cancer cells. However, the apoptosis induction was low and directly correlated with infectivity of Ad.mda-7. The objective of this study was to derive ovarian cancer targeted infectivity-enhanced adenoviral vectors encoding mda-7 and evaluate their enhancement in therapeutic efficacy for ovarian carcinoma. METHODS: Infectivity-enhanced adenoviral vectors encoding mda-7 Ad.RGD.mda-7 and Ad.RGD.pK7.mda-7 were derived by incorporation of RGD and or RGD and Pk7 motifs in the fiber knobs by genetic modification. Viruses were validated by PCR for presence of mda-7 and by Western blot for expression of MDA-7 protein. To test the enhancement of therapeutic efficacy of these viruses, a panel of human ovarian carcinoma cells, OV-4, HEY, SKOV3, SKOV3.ip1, were infected by either Ad.mda-7 or Ad.RGD.mda-7 and Ad.RGD.pK7.mda-7 or their respective control viruses and the cell killing was evaluated by crystal violet staining in vitro. Further, therapeutic efficacy was evaluated in vivo using human ovarian cancer xenograft mouse models. RESULTS: Both Ad.RGD.pK7.mda-7 and Ad.RGD.mda-7 showed significant increase in cell killing in vitro compared to unmodified Ad.mda-7 with Ad.RGD.pK7.mda-7 showing highest cell killing. Further, Ad.RGD.pK7.mda-7 showed a significant increase in survival of mice bearing human ovarian cancer xenografts compared to Ad.mda-7 and other control groups. CONCLUSION: Infectivity-enhanced Ad.RGD.mda-7 and Ad.RGD.pK7.mda-7 viruses significantly enhanced ovarian cancer tumor cell killing in vitro. Significant prolongation of survival by Ad.RGD.pK7.mda-7 in murine ovarian cancer models demonstrates the high clinical translational potential of these viruses for ovarian cancer therapy.     

The genetic heterogeneity of uterine leiomyomata

Research investigating the genetics of UL has already been successful in gathering epidemiologic evidence for heritability, establishing the clonal and mosaic nature of these tumors, correlating genotypic and phenotypic characteristics, defining cytogenetic subgroups, and identifying specific genes involved in tumorigenesis. Although UL are known to be benign tumors, the impact they have on the lives of so many women can only be described as "malignant". For this reason, continuing the quest to ascertain the genes, functions, and mechanisms integral to UL development is absolutely imperative. Genetic tests for personalized medical management of women with fibroids is at the threshold for providing the most appropriate treatments (Fig. 3), and combined with developing less invasive therapies portends a brighter future for a major health problem for women.     

Computational modelling approaches as a potential platform to understand the molecular genetics association between Parkinson’s and Gaucher diseases

Gaucher’s disease (GD) is a genetic disorder in which glucocerebroside accumulates in cells and specific organs. It is broadly classified into type I, type II and type III. Patients with GD are at high risk of Parkinson’s disease (PD), and the clinical and pathological presentation of GD patients with PD is almost identical to idiopathic PD. Several experimental models like cell culture, animal models, and transgenic mice models were used to understand the molecular mechanism behind GD and PD association; however, such mechanism remains unclear. In this context, based on literature reports, we identified the most common mutations K198T, E326K, T369M, N370S, V394L, D409H, L444P, and R496H, in the Glucosylceramidase (GBA) protein that are known to cause GD1, and represent a risk of developing PD. However, to date, no computational analyses have designed to elucidate the potential functional role of GD mutations with increased risk of PD. The present computational pipeline allows us to understand the structural and functional significance of these GBA mutations with PD. Based on the published data, the most common and severe mutations were E326K, N370S, and L444P, which further selected for our computational analysis. PredictSNP and iStable servers predicted L444P mutant to be the most deleterious and responsible for the protein destabilization, followed by the N370S mutation. Further, we used the structural analysis and molecular dynamics approach to compare the most frequent deleterious mutations (N370S and L444P) with the mild mutation E326K. The structural analysis demonstrated that the location of E326K and N370S in the alpha helix region of the protein whereas the mutant L444P was in the starting region of the beta sheet, which might explain the predicted pathogenicity level and destabilization effect of the L444P mutant. Finally, Molecular Dynamics (MD) at 50 ns showed the highest deviation and fluctuation pattern in the L444P mutant compared to the two mutants E326K and N370S and the native protein. This was consistent with more loss of intramolecular hydrogen bonds and less compaction of the radius of gyration in the L444P mutant. The proposed study is anticipated to serve as a potential platform to understand the mechanism of the association between GD and PD, and might facilitate the process of drug discovery against both GD and PD.     

External Cephalic Version: A Dying Art Worth Reviving

Purpose

Breech presentation is the most common abnormal presentation occurring in 3–4% of all deliveries. Incidence of caesarean section for breech presentation has increased markedly in the last few decades. Attempting external cephalic version (ECV) reduces the chance of non-cephalic presentation at term, thus reducing the rate of caesarean sections.

Methods

Prospective study was conducted in secondary healthcare centre, in rural set-up from August 2013 to August 2015. A total of 52 patients were enrolled into the study.

Results

ECV was successful in 32 out of 52 patients with overall success of 61.5%. Out of the 32 successful ECVs, 24 patients delivered vaginally (75%) (p value 0.00), 6 patients delivered by caesarean section, and 2 patients were lost to follow-up. Transverse lie had 100% success rate for ECV (p value 0.005). Gravidity, placental position, gestational age and use of tocolytics did not influence the success rate of ECV. Most common problem observed during the procedure was abdominal discomfort.

Conclusion

ECV is a safe procedure with high percentage of patients delivering vaginally after successful version. Hence, acquiring skills in ECV should be considered mandatory in the postgraduate training of future obstetricians.

     

Online Public Health Preparedness Training Programs: An Evaluation of User Experience with the Technological Environment

Objectives:

Several public health education programs and government agencies across the country have started offering virtual or online training programs in emergency preparedness for people who are likely to be involved in managing or responding to different types of emergency situations such as natural disasters, epidemics, bioterrorism, etc. While such online training programs are more convenient and cost-effective than traditional classroom-based programs, their success depends to a great extent on the underlying technological environment. Specifically, in an online technological environment, different types of user experiences come in to play—users’ utilitarian or pragmatic experience, their fun or hedonic experience, their social experience, and most importantly, their usability experience—and these different user experiences critically shape the program outcomes, including course completion rates. This study adopts a multi-disciplinary approach and draws on theories in human computer interaction, distance learning theories, usability research, and online consumer behavior to evaluate users’ experience with the technological environment of an online emergency preparedness training program and discusses its implications for the design of effective online training programs. .

Methods:

Data was collected using a questionnaire from 377 subjects who had registered for and participated in online public health preparedness training courses offered by a large public university in the Northeast.

Results:

Analysis of the data indicates that as predicted, participants had higher levels of pragmatic and usability experiences compared to their hedonic and sociability experiences. Results also indicate that people who experienced higher levels of pragmatic, hedonic, sociability and usability experiences were more likely to complete the course(s) they registered for compared to those who reported lower levels.

Discussion:

The study findings hold important implications for the design of effective online emergency preparedness training targeted at diverse audiences including the general public, health care and public health professionals, and emergency responders. Strategies for improving participants’ pragmatic, hedonic, sociability and usability experiences are outlined.

Conclusion:

There are ample opportunities to improve the pragmatic, hedonic, sociability and usability experiences of the target audience. This is critical to improve the participants’ learning and retention as well as the completion rates for the courses offered. Online emergency preparedness programs are likely to play a crucial role in preparing emergency responders at all levels in the future and their success has critical implications for public health informatics.