Establishment of Doxorubicin Resistant Stem-like Cell line from MCF-7 Cells

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Population study of 1311 C/T polymorphism of Glucose 6 Phosphate Dehydrogenase gene in Pakistan – an analysis of 715 X-chromosomes

<p>Abstract</p> <p>Background</p> <p>Nucleotide 1311 polymorphism at exon 11 of G6PD gene is widely prevalent in various populations of the world. The aim of the study was to evaluate 1311 polymorphism in subjects carrying G6PD Mediterranean gene and in general population living in Pakistan.</p> <p>Results</p> <p>Patients already known to be G6PD deficient were tested for 563C-T (G6PD Mediterranean) and 1311 C-T mutation through RFLP based PCR and gene sequencing. A control group not known to be G6PD deficient was tested for 1311C/T only.</p> <p>C-T transition at nt 1311 was detected in 60/234 X-chromosomes with 563 C-T mutation (gene frequency of 0.26) while in 130 of normal 402 X-chromosomes (gene frequency of 0.32).</p> <p>Conclusion</p> <p>We conclude that 1311 T is a frequent polymorphism both in general populations and in subjects with G6PD Mediterranean gene in Pakistan. The prevalence is higher compared to most of the populations of the world. The present study will help in understanding genetic basis of G6PD deficiency in Pakistani population and in developing ancestral links of its various ethnic groups.</p

Community based interventions for the prevention and control of tuberculosis

In 2012, an estimated 8.6 million people developed tuberculosis (TB) and 1.3 million died from the disease. With its recent resurgence with the human immunodeficiency virus (HIV); TB prevention and management has become further challenging. We systematically evaluated the effectiveness of community based interventions (CBI) for the prevention and treatment of TB and a total of 41 studies were identified for inclusion. Findings suggest that CBI for TB prevention and case detection showed significant increase in TB detection rates (RR: 3.1, 95% CI: 2.92, 3.28) with non-significant impact on TB incidence. CBI for treating patients with active TB showed an overall improvement in treatment success rates (RR: 1.09, 95% CI: 1.07, 1.11) and evidence from a single study suggests significant reduction in relapse rate (RR: 0.26, 95% CI: 0.18, 0.39). The results were consistent for various study design and delivery mechanism. Qualitative synthesis suggests that community based TB treatment delivery through community health workers (CHW) not only improved access and service utilization but also contributed to capacity building and improving the routine TB recording and reporting systems. CBI coupled with the DOTS strategy seem to be an effective approach, however there is a need to evaluate various community-based integrated delivery models for relative effectiveness

Relationship of Caregivers' Perceived Stress and Burden among Stroke Survivors: A prospective Cross-Sectional Study

Objective: To determine the relationship between perceived stress and burden among caregivers of stroke survivors residing in Lahore city of Pakistan. Methods: This prospective cross-sectional study was conducted at three health care institutes of Lahore, Pakistan from October 2021 to March 2022. The inclusion was limited to caregivers providing more than 6 hours of care per day to stroke survivors for at least one month duration after the discharge from hospital. The Zarit Caregiver burden interview and perceived stress scale were used to measure caregiver burden and perceived stress respectively. Results: Of 384 caregivers of stroke survivors, the mean age was 34.79 ± 5.80 years. Mild to moderate burden was observed in 364 (94.8%) and only 20 (5.2%) had moderate to severe burden. Similarly, moderate stress was observed in 353 (91.9%) and only 31 (8.1%) had severe stress. A significantly weak positive correlation was found between stress score and burden score (r=0.26, p-value <0.001). Furthermore, significantly weak positive correlation of burden and stress score was observed when stratified on the basis of age, gender, and relationship with the stroke survivor. Conclusion: In the current study, a weak positive correlation was observed between perceived stress and burden among caregivers of stroke survivors

Expression of the androgen receptor, pAkt, and pPTEN in breast cancer and their potential in prognostication

BACKGROUND: Importance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa. METHODS: This study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥ 5 years of follow-up (n = 82). RESULTS: Expression of AR, pAkt and pPTEN was observed in 47.5%, 81.3% and 50.6% of patients, respectively. AR-expressing tumors were low or intermediate in grade (P \u3c .001) and expressed ER (P = .002) and PR (P = .001). Patients with AR+ tumors had significantly higher OS (Mean OS = 10.2 ± 0.465 years) compared to patients with AR− tumors (Mean OS = 5.8 ± 0.348 years) (P = .047). Furthermore, AR-positivity was associated with improved OS in patients receiving endocrine therapy (P = .020). Patients with AR+ /pAkt+ /pPTEN− tumors, had increased OS (Mean OS = 7.1 ± 0.535 years) compared to patients with AR−/pAkt+/pPTEN− tumors (Mean OS = 5.1 ± 0.738 years). CONCLUSION: AR-expressing tumors are frequently characterized by low or intermediate grade tumors, expressing ER and PR. In addition, expression of AR, pAkt and pPTEN, could be considered in prognostication of patients with invasive BCa

Antioxidant, antimicrobial and antiproliferative activities of peel and pulp extracts of red and white varieties of Ipomoea batatas (L) Lam

Purpose: To investigate the antioxidant, antibacterial and anticancer potentials of methanol and ethanol extracts of the peel and pulp of red and white species of Ipomoea batatas (L.) fruit.Methods: Total phenolic contents and flavonoids were determined using chemical assays. Antioxidant studies were carried out using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, inhibition of linoleic acid peroxidation assay and reducing power assay. Antibacterial and antiproliferative activities of extracts were determined using disc diffusion and MDBK cancer cell line inhibition methods, respectively.Results: The extract of peels of red specie (PERS) showed total phenolic contents (TPC) 8.9 mg gallic acid equivalent (GAE)/g dry extract and flavonoids 6.5 mg catechin equivalent (CE)/g dry extract. The extract of PERS also showed promising DPPH free radical scavenging activity, inhibition of linoleic acid peroxidation and reducing power activity. However, mild antibacterial and anti-proliferative activities were noted except that the extract showed significant inhibition of Bacillus subtilis growth.Conclusion: The results indicate that the peel and the pulp of red sweet potato (SP) specie are rich in antioxidants and can potentually be processed as antioxidant food supplements.Keywords: Ipomoea batatas (L.) Lam, Sweet potato, Phenolic content, Antioxidants, Antibacterial activity, Antiproliferative activit

Microwave-assisted solvent free efficient synthesis of 1,3,4-oxadiazole-2(3H)-thiones and their potent in vitro urease inhibition activity

An efficient solvent free microwave assisted synthesis of 5-substituted-1,3,4-oxadiazole-2(3H)-thiones (2a-2r) from hydrazides and carbon disulfide has been accomplished in good to excellent yield. The urease inhibition activity of the resulting compounds was investigated. Preliminary bioassay indicated that the compound 2j bearing 2-bromo substituent is the most active inhibitor exhibiting IC50 12.60 ± 0.92 μM

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Cytogenetic abnormalities associated with reproductive failure in Pakistani population: experience of a tertiary care hospital

Constitutional chromosomal abnormalities play a significant role in causing reproductive anomalies in individuals of reproductive age. With the rapid advancement of genome engineering techniques, it has now become possible to cure different genetic disorders. However, very limited data is available regarding the prevalence of such aberrations in the Pakistani population. Considering this factor, this retrospective analysis was undertaken to elucidate the type and prevalence rate of such abnormalities in our population. A total of 241 individuals, who were referred to the Liaquat National Hospital, from January 2017 to December 2021, with a history of infertility or miscarriages, were evaluated using the standard GTG banding technique. The results revealed a notably high percentage 44(18.2%) of chromosomal abnormalities in our population. Surprisingly, the frequency of these anomalies was observed to be higher in males than in females. ---Continu

MP39-17 MECP2 Silencing in high grade bladder Cancer derived HTB-5 Cell line affects Cellular Proliferation and Migratory ability

DNA methylation patterns and chromatin structure is significantly altered in many human neoplasms including bladder cancer. Aberrant promoter hypermethylation of tumor suppressor genes is now a well established mechanism of gene inactivation. Methyl binding proteins are believed to act as interpreters of DNA methylation signal. The methyl binding protein MeCP2 has been shown to bind specifically to the 5mCpGs that are flanked by A/T residues. (Klose R et al., 2005) and mediates transcriptional repression by recruiting histone deacetylases (Adrian Bird at al.,1998) and thus, serving as a bridge between two major regulatory mechanisms of gene expression-DNA methylation and histone deacetylation