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

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

Gender inequality and the risk of HIV among married couples in North India

This study investigated the distribution and determinants of HIV risks among married couples in North India. Gender inequality emerged as a potential driver of HIV risks in this region. Data collection took place in 2003 in a probability survey of 3,385 couples living in India’s most populous state – Uttar Pradesh – and Uttaranchal. Couples’ analyses utilizing generalized estimating equations showed that compared with husbands, wives were less knowledgeable about HIV (OR=0.31, 95% CI= 0.27–0.36), more likely to consider themselves at risk for infection (OR=6.86, 95% CI= 4.65–10.13), and less likely to feel that a wife had the right to refuse sex with her husband (OR=0.50, 95% CI= 0.44–0.58). The proportion of husbands reporting non-marital sex in the past year was 7.1% and transactional sex in the past year, 2.2%. Among their wives, 73.4% were unaware of their husbands’ non-marital sexual behaviors and only 28.9% of husbands reported condom use during their last non-marital sexual encounter. Logistic regression analyses showed that husbands’ alcohol use, husbands’ mobility, and urban residence were positively associated with husbands’ non-marital sexual behaviors adjusting for other covariates. The data demonstrate that HIV prevention programs among couples in North India should consider both sexual risks and gender inequalities which potentially fuel HIV spread in this region

Gender-Based Power and Couples’ HIV Risk in Uttar Pradesh and Uttarakhand, North India

Gender inequality is a long-recognized driver of the HIV epidemic. However, few studies have investigated the association between gender-based power and HIV risk in India, which has the world's third largest HIV epidemic

Intergenerational Profiles of Socioeconomic (Dis)advantage and Obesity During the Transition to Adulthood

Investigations of socioeconomic status (SES) and health during the transition to adulthood in the United States are complicated by the later and more varied transitions in residence, employment, schooling, and social roles compared with previous generations. Parental SES is an important influence during adolescence but cannot sufficiently capture the SES of the independent young adult. Typical, single SES indicators based on income or education likely misclassify the SES of young adults who have not yet completed their education or other training, or who have entered the labor force early with ultimately lower status attainment. We use a latent class analysis (LCA) framework to characterize five intergenerational SES groups, combining multidimensional SES information from two time points—that is, adolescent (parental) and young adult (self) SES data. Associations of these groups with obesity, a high-risk health outcome in young adults, revealed nuanced relationships not seen using traditional intergenerational SES measures. In males, for example, a middle-class upbringing in adolescence and continued material advantage into adulthood was associated with nearly as high obesity as a working poor upbringing and early, detrimental transitions. This intergenerational typology of early SES exposure facilitates understanding of SES and health during young adulthood

HIV Testing Among Young Adults in the United States: Associations with Financial Resources and Geography

We estimated prevalence and odds ratios for self-reported HIV testing among sexually experienced young adults using nationally representative data obtained from Wave III of the National Longitudinal Study of Adolescent Health (Add Health). The prevalence of testing in the past year was 18.8%

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

Medication, reperfusion therapy and survival in a community-based setting of hospitalised myocardial infarction

To examine the survival benefit of multiple medical therapies in a large, community-based population of validated myocardial infarction (MI) events