Prostate cancer and glutathione S-transferase deletions

GSTM1 and GSTT1 gene polymorphisms have been studied in many populations to evaluate their association with prostate cancer risk with contrasting results. The current study was aimed to find out the association of GSTM1 and GSTT1 gene polymorphisms with prostate cancer in Pakistani men. This case control study included pathologically confirmed prostate cancer patients and age matched male controls. Epidemiological data was collected by a standard questionnaire and presence or absence of GSTM1 and GSTT1 gene was observed by multiplex PCR using CYP1A1 as housekeeping gene. Prostate cancer was more prevalent in age of >60 years and most of the patients were at stage IV (70 %) and have undergone surgery. Family history of cancer, smoking, metastasis and surgery were found to be significant (P0.05) with prostate cancer risk. No significant association was found when comparing GSTM1 (OR=0.78) and GSTT1 (OR=0.89) gene deletions with prostate cancer risk. Smoking and TNM staging were also not associated with deletion of GSTM1 and GSTT1 genes. Comparison of dual null deletion of both genes with prostate cancer also showed nonsignificant associations. Deletion of GSTM1 gene at stage IV prostate cancer patients was significantly higher compared with other stages of cancer while no significance was shown by GSTT1 gene deletion. GSTM1, GSTT1 and deletion of both GSTM1 and GSTT1 genes do not contribute towards increased risk of prostate cancer in Pakistani population

A meta-analysis and experimental data for multidrug resistance genes in breast cancer

Background: Increasing trend of breast cancer incidence worldwide is a known fact. This curable disease may become fatal if drug resistance is developed leading to metastatic cancerous tissue. Objective: This is a two parts study; a meta-analysis exploring association of drug resistance (mdr1 and ABCG2) genes with breast cancer and mutational association with molecular subtypes of cancer. Methods: PCR-SSCP for genomic polymorphisms and RT-PCR for expression analysis were performed. Results: C3435T polymorphism of mdr1 gene was most commonly studied mutation with contradictory results. Association of ABCG2 gene mutations with untreated breast cancer was reported only by one study so far. Regarding current genomic analysis of mdr1 gene, three novel mutations were found in exon 12 and 2 mutations were found in exon 26. In ABCG2 gene, addition of C and T were found in intron 8 at the intron-exon junction. A positive correlation was observed between these mutations and tumor grade. Levels of mRNA expression revealed that they were over expressed in cancerous tissues compared with controls. Conclusion: These findings suggest that these genes are associated with breast cancer. Keywords: Expression; mutations; mdr1; ABCG2; breast cancer

Antibacterial evaluation of three widespread weeds Mazus japonicus, Fumaria indica and Vicia faba from Pakistan

Present study was carried out to explore the antibacterial potential of three weeds Mazus japonicus, Fumaria indica and Vicia sativa grown widely in Pakistan. Different extracts (aqueous, methanolic and petroleum ether) of the respective weeds were prepared and tested against nine bacterial strains using agar well diffusion assay. Bacterial strains included both gram positive (Staphylococcus aureus, Bacillus anthracis, Bacillus megaterium, Enterococcus faecium, Enterrococcus faecalis and Enteroccocus sp) and gram negative (Pseudomonas putida, Escherichia coli and Escherichia coli top10) bacteria. Ten different concentrations of each extracts were used. Enterococcus faecalis JH22 and Bacillus megaterium MB141 were the most resistant bacteria while Escherichia coli top10 was found highly susceptible and inhibited by all three extracts of Mazus japonicas and Fumaria indica. Vicia sativa was effective only against Staphylococcus aureus and Pseudomonas putida at limited crude extract concentration while all other strains showed resistance against different extracts of the respective plant. Amongst the plant extracts screened for antibacterial activity, methanolic extracts showed best antibacterial activity whereas aqueous and petroleum ether were found least active. This study significantly supports the usage of these widespread weeds as traditional medicines for various bacterial infections.Â

The project to understand and research preterm pregnancy outcomes and stillbirths in South Asia (PURPOSe): a protocol of a prospective, cohort study of causes of mortality among preterm births and stillbirths

Background: In South Asia, where most stillbirths and neonatal deaths occur, much remains unknown about the causes of these deaths. About one-third of neonatal deaths are attributed to prematurity, yet the specific conditions which cause these deaths are often unclear as is the etiology of stillbirths. In low-resource settings, most women are not routinely tested for infections and autopsy is rare.Methods: This prospective, cohort study will be conducted in hospitals in Davengere, India and Karachi, Pakistan. All women who deliver either a stillbirth or a preterm birth at one of the hospitals will be eligible for enrollment. With consent, the participant and, when applicable, her offspring, will be followed to 28-days post-delivery. A series of research tests will be conducted to determine infection and presence of other conditions which may contribute to the death. In addition, all routine clinical investigations will be documented. For both stillbirths and preterm neonates who die ≤ 28 days, with consent, a standard autopsy as well as minimally invasive tissue sampling will be conducted. Finally, an expert panel will review all available data for stillbirths and neonatal deaths to determine the primary and contributing causes of death using pre-specified guidance.Conclusion: This will be among the first studies to prospectively obtain detailed information on causes of stillbirth and preterm neonatal death in low-resource settings in Asia. Determining the primary causes of death will be important to inform strategies most likely to reduce the high mortality rates in South Asia

Factors influencing in-hospital length of stay and mortality in cancer patients suffering from febrile neutropenia

Introduction: Febrile neutropenia (FN) is a major complication of chemotherapy, costly in terms of morbidity, mortality and associated financial expenditure. The present study was conducted with the goal of highlighting FN as a serious problem in Pakistan, with the longer term objective of improved cancer survival, reduction in length of stay (LOS) in hospital, morbidity, mortality and costs in our existing developing country scenario. Methods: A cross-sectional descriptive study was conducted on Patients, \u3e or =18 years, admitted with FN as a consequence of chemotherapy at a referral hospital in Karachi from 1st September 2006 to 30th April 2007. Results: A total of 80 Patients [43 (53.8%) males and 37 (46.2%) females] were selected. The mean age was 47.4 (SD +/-16.6, range 18-79) years. Sixty eight Patients (86%) were \u3c or = 65 years, 50% were \u3c or = 50 years. Overall, inhospital mortality was 11%, 4% for Patients on granulocyte colony stimulating factor (G-CSF) prophylaxis as against 20% for those without. The cause of death was either pneumonia or septic shock. Mean LOS was 7.53 (SD +/-3.8, range 2-17) days. Hematological malignancies, older age, severity of dehydration, pneumonia and culture positivity were significantly associated with LOS and death. Those above 50 years of age were 1.5 times as likely to be hospitalized longer and \u3e three times as likely to die. Bacteremia conferred a 5-fold and pneumonia an 8-fold increase in the risk of death. Conclusion: The results of this study indicate that age, vital instability, dehydration, high creatinine, culture positivity and hematological malignancies are high risk factors in chemotherapy induced FN. Identification of FN risk factors with poor outcomes may help in devising protocols for modified dosage or including GCFs initially. This may help reduce the cost of cancer care as well as mortality and morbidity. Prospective studies of FN in multiple centers in Pakistan may be beneficial in evaluating these risk factors further

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Brain Image Compression: A Brief Survey

Abstract: Brain image compression is known as a subfield of image compression. It allows the deep analysis and measurements of brain images in different modes. Brain images are compressed to analyze and diagnose in an effective manner while reducing the image storage space. This survey study describes the different existing techniques regarding brain image compression. The techniques come under different categories. The study also discusses these categories

DataSheet_1_Correlation of ERCC5 polymorphisms and linkage disequilibrium associated with overall survival and clinical outcome to chemotherapy in breast cancer.docx

PurposeERCC5 is a DNA endonuclease and nucleotide excision repair gene; its mutations lead to a lack of activity by this enzyme, causing oxidative DNA damage. This study aimed to assess the role of four selected single nucleotide polymorphisms (SNPs) in ERCC5 and their linkage disequilibrium associated with survival analysis and clinical outcomes in breast cancer.Patients and methodsFour SNPs (rs751402, rs17655, rs2094258, and rs873601) of the ERCC5 gene were analyzed using the PCR-RFLP technique, followed by sequencing in 430 breast cancer (BC) cases and 430 cancer-free individuals. Statistical analysis was performed using MedCalc 17 and SPSS version 24, while bioinformatic analysis of linkage disequilibrium was performed using Haploview software 4.2.ResultsMultivariate analysis showed that the rs751402 and rs2094258 polymorphisms were significantly associated with an elevated risk of BC (P 0.001). Survival analysis revealed that rs751402 and rs2094258 had longer overall survival periods (P ConclusionThe current results suggest that variations in ERCC5 may contribute to BC development and that their genetic anomalies may be associated with cancer risk and may be used as a biomarker of clinical outcome.</p

Breast Cancer: Epidemiology, Risk Factors and Survival Analysis in the Pakistani Population

Objective: To find out the association of genetic, reproductive and socio demographic factors with breast cancer in Pakistani women along with the sur- vival percentage of patients having breast cancer. Methodology: A case control study was carried out for a period of 3 years. Data were collected from different hospitals in Pakistan and the survival rate was determined by having direct contact with patients through telephone calls. For the estimation of survival probability Kaplan-Meier curve was used. Association of various demographic and epidemiological factors with breast cancer occurrence was estimated by using the odds ratio (OR) and 95% confidence interval (CI). Various tests used to find out the significance of results included student t-test, chi-square test, Fisher exact test and ANOVA. A statistical tool SPSS version 22 was used to analyze the data and results orientation. Results: The mean age for breast cancer diagnosis 47.3±11.8 years of age was found as mean age for breast cancer diagnosis. Higher BMI was the major contributing factors in developing breast cancer (OR=3.5, 95% CI=2.6-4.5). Significant risk factors found to be associated with the breast cancer included long reproductive period (menarche to menopause), family history of disease and habit of passive smoking (P<0.05). Out of 448 married patients, 23% were nulliparous and 26% of patients did not have a lactation history. Chemotherapy along with radiotherapy and surgery have been found to be effective methods for breast cancer treatment (80% survival). Conclusion: Present study concluded that age, body mass index, oral contraceptives usage, lactation duration, reproductive duration and marital status of the female are significant factors in developing breast cancer in Pakistani women. Keywords: Breast Cancer, Nulliparous, Chemotherapy, Radiotherapy