Evaluation of a successful intervention for sustainability and effects in post research phase.

INTRODUCTION: Promoting appropriate use of drugs is an essential element in achieving quality of health and medical cares for patients and the community, and also to minimize financial burden. OBJECTIVE: The objective of this paper is to assess the successful intervention for sustainability and effects in post research phase. To address these problems, a variety of educational, managerial and regulatory strategies to improve prescribing have been tried in Nepal. When training is combined with a managerial intervention i.e. peer-group discussion, it results into improved changes in prescribing practices of paramedics in several practices. METHODOLOGY: A prospective, three-way design study consisting of small group training, small group training followed by peer-group discussion and control was conducted in three regions of Nepal including one hill and two terai (plains) districts from each region. The study included all health post from the sampled districts, making 80 health posts the study population. RESULTS: The study revealed the effectiveness of the peer-group discussion approach in improving the prescribing practices. An assessment to identify the sustainability of the strategy and its effect within the district healthcare system after the completion of the research phase was undertaken. The study found that peer-group discussion was discontinued in all targeted districts and the improved practices were not sustained after the completion of the research. Various reasons have been found for not continuing the effective intervention.     

Resveratrol inhibits rhabdomyosarcoma cell proliferation.

Rhabdomysarcoma is the most common soft tissue tumour in children under the age of 15. Although the introduction of multimodal treatment programmes, including chemotherapy, radiation therapy and excision have increased the overall survival, the chemotherapeutic agents currently used for the treatment of rhabdomyosarcoma exhibit considerable toxicity. The aim of this study was to investigate the effects and possible mechanism(s) of action of resveratrol on human embryonal rhabdomyosarcoma (RD) cells. Resveratrol is a natural polyphenolic compound produced in a number of edible plants and has received considerable attention as a potential chemopreventive and/or chemotherapeutic agent against various types of cancers. In the present study, resveratrol was shown to inhibit cell proliferation of RD cells in a dose-dependent manner with an IC50 of 48.1 micromol/l and induce an arrest in the S/G2 phase of the cell cycle. As evident from immunocytochemical data, resveratrol treatment increased the size of the RD cells. Furthermore, resveratrol treatment resulted in a significant downregulation of cyclin B expression as demonstrated by western blot analyses. In conclusion, the present study shows that resveratrol exerts a strong inhibition of rhabdomyosarcoma cell proliferation in part by arresting cells in S/G2 phase of the cell cycle. These findings warrant further investigation to establish potential use of resveratrol as a relatively non-toxic chemotherapeutic agent for the treatment of rhabdomyosarcoma.     

Women's empowerment and fertility preferences of married women: analysis of demographic and health survey’2016 in Timor-Leste

A recently independent state, Timor-Leste, is progressing towards socioeconomic development, prioritizing women empowerment while its increased fertility rate (4.1) could hinder the growth due to an uncontrolled population. Currently, limited evidence shows that indicators of women''s empowerment are associated with fertility preferences and rates. The objective of this study was to assess the association between women empowerment and fertility preferences of married women aged 15 to 49 years in Timor-Leste using nationally representative survey data. The study was conducted using the data of the latest Timor-Leste Demographic and Health Survey 2016. The study included 4040 rural residents and 1810 urban residents of Timor-Leste. Multinomial logistic regression has been performed to assess the strength of association between the exposures indicating women''s empowerment and outcome (fertility preference). After adjusting the selected covariates, the findings showed that exposures that indicate women empowerment in DHS, namely, the employment status of women, house and land ownership, ownership of the mobile phone, and independent bank account status, contraceptive use, and the attitude of women towards negotiating sexual relations are significantly associated with fertility preferences. The study shows higher the level of education, the less likely were the women to want more children, and unemployed women were with a higher number of children. Our study also found that the attitude of violence of spouses significantly influenced women''s reproductive choice. However, employment had no significant correlation with decision-making opportunities and contraceptive selection due to a lack of substantial data. Also, no meaningful data was available regarding decision-making and fertility preferences. Our findings suggest that women''s empowerment governs decision-making in fertility preferences, causing a decline in the fertility rate.     

Molecular docking and dynamics based approach for the identification of kinase inhibitors targeting PI3Kα against non-small cell lung cancer: a computational study

Non-small cell lung cancer (NSCLC) is an obscure disease whose incidence is increasing worldwide day by day, and PI3Kα is one of the major targets for cell proliferation due to the mutation. Since PI3K is a class of kinase enzyme, and no in silico research has been performed on the inhibition of PI3Kα mutation by small molecules, we have selected the protein kinase inhibitor database and performed the energy minimization process by ligand preparation. The key objective of this research is to identify the potential hits from the protein kinase inhibitor library and further to perform lead optimization by a molecular docking and dynamics approach. And so, the protein was selected (PDB ID: 4JPS), having a unique inhibitor and a specific binding pocket with amino acid residue for the inhibition of kinase activity. After the docking protocol validation, structure-based virtual screening by molecular docking and MMGBSA binding affinity calculations were performed and a total of ten hits were reported. Detailed analysis of the best scoring molecules was performed with ADMET analysis, induced fit docking (IFD) and molecular dynamics (MD) simulation. Two molecules – 6943 and 34100 – were considered lead molecules and showed better results than the PI3K inhibitor Copanlisib in the docking assessment, ADMET analysis, and molecular dynamics simulation. Furthermore, the synthetic accessibility of the two compounds – 6943 and 34100 – was investigated using SwissADME, and the two lead molecules are easier to synthesize than the PI3K inhibitor Copanlisib. Computational drug discovery tools were used for identification of kinase inhibitors as anti-cancer agents for NSCLC in the present research.

Non-small cell lung cancer (NSCLC) is an obscure disease whose incidence is increasing worldwide day by day, and PI3Kα is one of the major targets for cell proliferation due to the mutation.     

Expedient approach for trans-esterification of β-keto esters under solvent free conditions using silica supported boric acid (SiO2–H3BO3) as a recyclable catalyst

A highly efficient trans-esterification of β-keto methyl/ethyl esters with primary, secondary, allylic, benzylic and chiral alcohols has been carried out in excellent yields under solvent-free conditions using silica supported boric acid as a heterogeneous catalyst. The surface morphology of the silica-boric acid catalyst (fresh and recycled) has been characterized by SEM and EDX techniques. This sustainable protocol resulted in a remarkable enhancement in the synthetic efficiency (87–95% yield) with high purity and eliminating the use of an environmentally toxic solvent. The work up procedure is very simple and the catalyst has been successfully recovered and recycled. The present methodology is also applicable for trans-esterification with chiral alcohols on a multi-gram scale without compromising the yield. Noteworthy features of this protocol are simple operational procedure, minimizing production of chemical waste, mild reaction conditions, easy preparation of the catalyst and its recyclability up to five cycles without any appreciable loss of catalytic activity.

A simple, mild, high yielding and minimizing chemical waste procedure for trans-esterification of β-keto methyl/ethyl esters with alcohol groups was developed under solvent-free condition using silica-boric acid as recyclable heterogeneous catalyst.     

Glycosmis arborea extract as a hepatoprotective agent

Glycosmis arborea is a plant possessing various medicinal properties. The aim of the present study was to investigate the hepatoprotective efficacy of the butanol extract obtained from the aerial parts of the plant. The test sample was prepared by extracting the material through different steps. The extract thus obtained was dissolved in normal saline. Albino rats were prophylactically treated with the extract (i.p.) for 3 weeks. At the end of 3rd week all the groups were injected with hepatotoxic agents. After 48 h of injection, blood was collected and livers were taken out. Different enzymes in the serum were assayed and histopathological study was performed with liver. Glycosmis arborea extract was able to overcome the toxic effects of hepatotoxic agents in terms of lowering the levels of serum GPT, alkaline phosphatase and increased level of SOD in serum. TBARS generation in liver was also altered. Moreover, necrosis of liver produced by carbon tetrachloride was reversed by the extract.     

Drug-prescribing patterns during pregnancy in the tertiary care hospitals of Pakistan: a cross sectional study

Background

Low birth weight (LBW) is considered as a major multifaceted public health concern. Seventy-two percent of LBW infants are born in Asia. An estimation of 8% LBW infants has been reported for Eastern Mediterranean region including Iran. This study investigated contributory factors of LBW in singleton term births in Tehran, Iran. Tehran is a multicultural metropolitan area and a sample from the general population in Tehran could be regarded as a representative sample of urban population in Iran.

Methods

This was a retrospective study using data from 15 university maternity hospitals in Tehran, Iran. Data on all singleton term births in these hospitals were extracted from case records during a one calendar year. Study variables included: maternal age, maternal educational level, history of LBW deliveries, history of preterm labor, cigarette smoking during pregnancy, number of parities, chronic diseases and residential area (Tehran versus suburbs of Tehran). In order to examine the relationship between LBW and demographic and reproductive variables the adjusted logistic regression analysis was performed.

Results

In all, data for 3734 term pregnancies were extracted. The mean age of women was 25.7 (SD = 5.3) years and 5.2% of term births were LBW. In addition to association between LBW and maternal age, significant risk factors for LBW were: history of LBW deliveries [adjusted odds ratio (OR) = 2.53, 95% confidence interval (CI) = 1.06–6.03], smoking during pregnancy (OR = 4.64, 95% CI = 1.97–10.95) and chronic diseases (OR for hypertension = 3.70, 95% CI = 2.25–6.06, OR for others = 2.04, 95% CI = 1.09–3.83).

Conclusion

The findings indicate that in addition to maternal age, history of LBW deliveries; smoking during pregnancy and chronic diseases are significant determinants of LBW in this population. This is consistent with national and international findings indicating that maternal variables and risk behaviors during pregnancy play important roles on LBW.     

DRESS syndrome: a detailed insight

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a serious and potentially fatal adverse effect to therapeutic medications. The incidence of this condition varies among different ethnicities because of the difference in the genetic makeup. Though fever, rash and eosinophilia are essential features for the diagnosis of this syndrome, these vary from patient to patient along with the involvement of various organs such as liver, kidney, lungs, pancreas, etc. Some of the atypical features are dysphagia, agranulocytosis, and chylous ascites. Phenytoin, phenobarbitone, carbamazepine, and allopurinol are the most common drugs responsible for developing this syndrome, although the list is fairly long. Among the criteria used for the diagnosis of DRESS syndrome, European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) criteria is the most commonly used one. The management of this syndrome involves early removal of the causative agent and treatment with anti-histamines and emollients in the mild form, corticosteroids in the moderate form and plasmapheresis in the severe form along with other alternatives drugs. Healthcare professionals should be more vigilant about the early manifestations of this syndrome, as early diagnosis and treatment improve outcomes considerably.     

Simian Varicella Virus Pathogenesis in Skin during Varicella and Zoster

Primary simian varicella virus (SVV) infection and reactivation in nonhuman primates is a valuable animal model in the study of varicella zoster virus disease [varicella (chickenpox) and herpes zoster (shingles)]. To understand SVV pathogenesis in skin, we inoculated 10 rhesus macaques with SVV, resulting in varicella rash. After the establishment of latency, eight of the monkeys were immunosuppressed using tacrolimus with or without irradiation and prednisone and two monkeys were not immunosuppressed. Zoster rash developed in all immunosuppressed monkeys and in one non-immunosuppressed monkey. Five monkeys had recurrent zoster. During varicella and zoster, SVV DNA in skin scrapings ranged from 50 to 10⁷ copies/100 ng of total DNA and 2–127 copies/100 ng of total DNA, respectively. Detection of SVV DNA in blood during varicella was more frequent and abundant compared to that of zoster. During varicella and zoster, SVV antigens colocalized with neurons expressing β-III tubulin in epidermis, hair follicles, and sweat glands, suggesting axonal transport of the virus. Together, we have demonstrated that both SVV DNA and antigens can be detected in skin lesions during varicella and zoster, providing the basis for further studies on SVV skin pathogenesis, including immune responses and mechanisms of peripheral spread.