Study Of Phenothiazine On p53 Core Domain Mutant Y220C: Finding The Anti-tumor Activity Of Phenothiazine

The tumor suppressor protein p53 is a transcription factor that plays a key role in the prevention of cancer development. The p53 cancer mutation Y220C induces formation of a cavity on the protein's surface that can accommodate stabilizing small molecules. We have attempted with the help of virtual screening and molecular docking approach using Lamarckian Genetic Algorithm to elucidate the extent of specificity of p53 cancer mutation Y220C towards different class of Phenothiazines (an anti-cancer agent). 

The 393 residue p53 tumor suppressor protein exists in a dynamic equilibrium to form homotetramers. Each chain comprises several functional domains. The N terminal part of the protein consists of the trans-activation domain (residues 1–63) followed by a proline rich region (64– 92). The central (core) domain (p53 core domain) is responsible for binding. The C terminal part of p53 contains the tetramerization domain (residues 326–355) and the negative regulatory domain at the extreme C terminus (363–393), which contains phosphorylation and acetylation sites and regulates the DNA binding activity of p53.

The docking result of the study of 2,000 Phenothiazines demonstrated that the binding energies were in the range of -10.54 kcal/mol to -1.14 kcal/mol, with 8 molecules showing hydrogen bonds with the active site residues (Lys 164). All the selected 2000 inhibitors were selected on the basis of the structural specificity to the enzyme towards its substrate and inhibitors. Our research provides a blueprint for the design of more potent and specific drugs that rescue p53-Y220C

HIV as a Risk Factor for Multi-Drug Resistant Tuberculosis: A Systematic Review

Winstone Zulu is featured prominently in a tuberculosis (TB) and HIV awareness campaign sponsored by the Stop TB Partnership, a network of organizations, countries and donors that have made the elimination of tuberculosis a priority. He is a Zambian who contracted HIV and later acquired infection with TB. He managed to survive the coinfection when so many around him, including four of his brothers, died of tuberculosis in the 1990s. This defining experience led him to become a leading advocate for TB and HIV patients worldwide. Like those in his family, many people in sub-Saharan Africa and throughout the world who suffer from TB and HIV do not survive the deadly combination. The terrifying consequences of the two infections have now become even graver- a newer threat of multi-drug resistant TB (MDR-TB) jeopardizes what little control there is now over the dual epidemic. Understanding the relationship between HIV and MDR-TB has profound implications for the many people like Winstone Zulu's brothers, who have all but received a death sentence.Master of Public Healt

A Regional Multilevel Analysis: Can Skilled Birth Attendants Uniformly Decrease Neonatal Mortality?

Globally 40% of deaths to children under-five occur in the very first month of life with three-quarters of these deaths occurring during the first week of life. The promotion of delivery with a skilled birth attendant (SBA) is being promoted as a strategy to reduce neonatal mortality. This study explored whether SBAs had a protective effect against neonatal mortality in three different regions of the world

Early Sex Work Initiation and Condom Use among Alcohol-Using Female Sex Workers in Mombasa, Kenya: A Cross-Sectional Analysis

Objectives Early initiation of sex work is prevalent among female sex workers (FSWs) worldwide. The objectives of this study were to investigate if early initiation of sex work was associated with: (1) consistent condom use, (2) condom negotiation self-efficacy or (3) condom use norms among alcohol-using FSWs in Mombasa, Kenya. Methods In-person interviews were conducted with 816 FSWs in Mombasa, Kenya. Sample participants were: recruited from HIV prevention drop-in centres, 18 years or older and moderate risk drinkers. Early initiation was defined as first engaging in sex work at 17 years or younger. Logistic regression modelled outcomes as a function of early initiation, adjusting for drop-in centre, years in sex work, supporting others and HIV status. Results FSWs who initiated sex work early were significantly less likely to report consistent condom use with paying sex partners compared with those who initiated sex work in adulthood. There was no significant difference between groups in consistent condom use with non-paying sex partners. FSWs who initiated sex work early endorsed less condom negotiation self-efficacy with paying sex partners compared with FSWs who did not initiate sex work early. Conclusions Findings highlight a need for early intervention for at-risk youth and adolescent FSWs, particularly in relation to HIV sexual risk behaviours. Evidence-based interventions for adolescent FSWs or adult FSWs who began sex work in adolescence should be developed, implemented and evaluated

Early Sex Work Initiation and Violence against Female Sex Workers in Mombasa, Kenya

Between 20 and 40 % of female sex workers (FSWs) began sex work before age 18. Little is known concerning whether early initiation of sex work impacts later experiences in adulthood, including violence victimization. This paper examines the relationship between early initiation of sex work and violence victimization during adulthood. The sample included 816 FSWs in Mombasa, Kenya, recruited from HIV prevention drop-in centers who were 18 years or older and moderate-risk drinkers. Early initiation was defined as beginning sex work at 17 or younger. Logistic regression modeled recent violence as a function of early initiation, adjusting for drop-in center, age, education, HIV status, supporting others, and childhood abuse. Twenty percent of the sample reported early initiation of sex work. Although both early initiators and other FSWs reported commonly experiencing recent violence, early initiators were significantly more likely to experience recent physical and sexual violence and verbal abuse from paying partners. Early initiation was not associated with physical or sexual violence from non-paying partners. Many FSWs begin sex work before age 18. Effective interventions focused on preventing this are needed. In addition, interventions are needed to prevent violence against all FSWs, in particular, those who initiated sex work during childhood or adolescence

Early sex work initiation and condom use among alcohol-using female sex workers in Mombasa, Kenya: a cross-sectional analysis

Early initiation of sex work is prevalent among female sex workers (FSWs) worldwide. The objectives of this study were to investigate if early initiation of sex work was associated with: (1) consistent condom use, (2) condom negotiation self-efficacy or (3) condom use norms among alcohol-using FSWs in Mombasa, Kenya

Craniosacral therapy for migraine: Protocol development for an exploratory controlled clinical trial

Abstract Background Migraine affects approximately 20% of the population. Conventional care for migraine is suboptimal; overuse of medications for the treatment of episodic migraines is a risk factor for developing chronic daily headache. The study of non-pharmaceutical approaches for prevention of migraine headaches is therefore warranted. Craniosacral therapy (CST) is a popular non-pharmacological approach to the treatment or prevention of migraine headaches for which there is limited evidence of safety and efficacy. In this paper, we describe an ongoing feasibility study to assess the safety and efficacy of CST in the treatment of migraine, using a rigorous and innovative randomized controlled study design involving low-strength static magnets (LSSM) as an attention control intervention. Methods The trial is designed to test the hypothesis that, compared to those receiving usual care plus a treatment with low-strength static magnets (attention-control complementary therapy), subjects receiving usual medical care plus CST will demonstrate significant improvement in: quality-of-life as measured by the Headache Impact Test (HIT-6); reduced frequency of migraine; and a perception of clinical benefit. Criteria for inclusion are either gender, age > 11, English or Spanish speaking, meeting the International Classification of Headache Disorders (ICHD) criteria for migraine with or without aura, a headache frequency of 5 to 15 per month over at least two years. After an 8 week baseline phase, eligible subjects are randomized to either CST or an attention control intervention, low strength static magnets (LSSM). To evaluate possible therapist bias, videotaped encounters are analyzed to assess for any systematic group differences in interactions with subjects. Results 169 individuals have been screened for eligibility, of which 109 were eligible for the study. Five did not qualify during the baseline phase because of inadequate headache frequency. Nineteen have withdrawn from the study after giving consent. Conclusion This report endorses the feasibility of undertaking a rigorous randomized clinical trial of CST for migraine using a standardized CST protocol and an innovative control protocol developed for the study. Subjects are able and willing to complete detailed headache diaries during an 8-week baseline period, with few dropouts during the study period, indicating the acceptability of both interventions. Trial Registration ClinicalTrials.gov NCT0066523

Un análisis multinivel de población y deforestación en el Parque Nacional Sierra de Lacandón (Petén, Guatemala)

Este estudio examina los factores demográficos asociados con la deforestación en el Parque Nacional Sierra de Lacandón (PNSL), Guatemala, utilizando un análisis de regresión multinivel. Más del 10% del PNSL ha sido deforestado desde mediados de la década de 1980, a causa del crecimiento demográfico de la población campesina y su subsiguiente manejo de la tierra. Utilizando un análisis de regresión múltiple de dos niveles, este estudio examina datos demográficos y otras características de los hogares para explicar variaciones en el bosque roturado entre 241 fincas agrícolas en ocho comunidades en el PNSL. Esta metodología, novedosa en el estudio de uso del suelo en los trópicos, toma en cuenta la variación espacial entre comunidades, así como entre hogares. Al usar modelos de multinivel, se puede llegar a resultados mejores sobre los impactos de los factores, tanto a nivel de comunidad como a nivel de hogar sobre la deforestación, con implicaciones más adecuadas para políticas de desarrollo.Aquest estudi examina els factors demogràfics associats amb la desforestació al Parc Nacional Sierra de Lacandon (PNSL), Guatemala, mitjançant una anàlisi de regressió multinivell. Més del 10 % del PNSL ha estat desforestat des de la meitat de la dècada de 1980, com a conseqüència del creixement demogràfic i les pràctiques de gestió agrícola. Utilitzant una anàlisi de regressió múltiple de dos nivells, aquest estudi examina dades demogràfiques i unes altres característiques de les llars per explicar variacions en el bosc artigat entre 241 finques agrícoles en vuit comunitats al PNSL. Aquesta metodologia té en compte la variació especial entre comunitats i entre llars, i abans no havia estat mai aplicada als tròpics. El model de regressió multinivell pot ajudar a explicar millor els impactes de factors propis de les comunitats i de les llars en la desforestació, per tant, pot contribuir a millorar les polítiques de desenvolupament.Cette étude a examiné les facteurs démographiques associés au phénomène de déforestation du Parc National Sierra de Lacandón (PNSL, Guatemala) en utilisant une analyse de régression multi-niveau. Depuis le milieu des années 1980, plus de 10 % du PNSL a été déboisé par la croissance démographique de la population rurale, son besoin en surface et l'utilisation variée de la terre. En utilisant une analyse de régression multiple de deux niveaux, cette étude examine des données démographiques et plusieurs caractéristiques liées aux exploitations, dans le but d'expliquer les variations dans le parc défriché entre 241 propriétés agricoles dans huit communautés du PNSL. Cette méthodologie, nouvelle dans l'étude de l'usage du sol dans les tropiques, prend en compte la variation spatiale entre des communautés ainsi que des exploitations. En utilisant ces modèles de multi-niveaux, on peut arriver à de meilleurs résultats concernant les impacts des facteurs au niveau des communautés et des exploitations concernant la déforestation, avec des résultats plus adapatées pour les politiques de développement.The paper examines depopulation factors associated with deforestation in the Natural park of the Sierra de Lacandón (PNSL), using multi-level regresión analysis. More than 10 percent of the park area has been deforested since the mid 1980s because of rural population growth and agricultural practices. By means of a two-level regression analysis the study use dem ographic and other household data to explain variations in deforested land in 241 agricultural estates in 8 communities of the PNSL. The methodology, not applied before in the tropics, takes into account spatial variations between communities and households. Multilvel regression allows for better results on the impacts of socioeconomic factors on deforestation, both at the community and at the household levels with important implications for development policies

Gene by Sex Interaction for Measures of Obesity in the Framingham Heart Study

Obesity is an increasingly prevalent and severe health concern with a substantial heritable component and marked sex differences. We sought to determine if the effect of genetic variants also differed by sex by performing a genome-wide association study modeling the effect of genotype-by-sex interaction on obesity phenotypes. Genotype data from individuals in the Framingham Heart Study Offspring cohort were analyzed across five exams. Although no variants showed genome-wide significant gene-by-sex interaction in any individual exam, four polymorphisms displayed a consistent BMI association (P-values .00186 to .00010) across all five exams. These variants were clustered downstream of LYPLAL1, which encodes a lipase/esterase expressed in adipose tissue, a locus previously identified as having sex-specific effects on central obesity. Primary effects in males were in the opposite direction from females and were replicated in Framingham Generation 3. Our data support a sex-influenced association between genetic variation at the LYPLAL1 locus and obesity-related traits