An in silico approach to characterize nonsynonymous SNPs and regulatory SNPs in human TOX3 gene

Cancer is one of the deadliest complex diseases having multigene nature where the role of single-nucleotide polymorphism (SNP) has been well explored in multiple genes. TOX high mobility group box family member 3 (TOX3) is one such gene, in which SNPs have been found to be associated with breast cancer. In this study, we have examined the potentially damaging nonsynonymous SNPs(nsSNPs) in TOX3 gene using in silico tools, namely PolyPhen2, SNP&GO, PhD-SNP and PROVEAN, which were further confirmed by I-Mutant, MutPred1.2 and ConSurf for their stability, functional and structural effects. nsSNPs rs368713418 (A266D), rs751141352 (P273S, P273T), rs200878352 (A275T) have been found to be the most deleterious that may have a vital role in breast cancer. Premature stop codon producing SNPs (Q527STOP), rs1259790811 (G495STOP), rs1294465822 (S395STOP) and rs1335372738 (G8STOP) were also found having prime importance in truncated and malfunctional protein formation. We also characterized regulatory SNPs for its potential effect on TOX3 gene regulation and found nine SNPs that may affect the gene regulation. Further, we have also designed 3D models using I-TASSER for the wild type and four mutant TOX3 proteins. Our study concludes that these SNPs can be of prime importance while studying breast cancer and other associated diseases as well. They are required to be studied in model organisms and cell cultures, and may have potential importance in personalized medicines and gene therapy.

Angiographic anatomy of the coronary sinus venous system in adult Kashmiri population

Background: Knowledge of the coronary sinus venous anatomy is an important factor because of its relevance in electrophysiological procedures such as chronic resynchronisation therapy, mapping and ablation of arrhythmias. The advent of advanced invasive and interventional cardiac treatment and management tools for common disorders like heart failure has made understanding of coronary sinus anatomy necessary. The aim was to study the angiographic anatomy of coronary sinus and its tributaries in adult Kashmiri population and provide anatomical basis for cannulation of coronary sinus and its tributaries.Methods: Authors analysed the levophase angiogram of 150 subjects undergoing routine coronary angiography in the right anterior oblique and left anterior oblique view with the necessary caudal or cranial angulations.Results: The coronary sinus was formed by the union of GCV+LMV in 93.3% of subjects and by the union of GCV+PLV in 6.7% of subjects. The GCV and the MCV were the most consistent tributaries present in all the subjects. The mean length of CS was 71.70±9.7 mm when it was formed by GCV+LMV and 70.18±14.98 mm in case of GCV+PLV. The diameter of the CS ostium was 8.48±1.21mm. The mean diameter of GCV was 2.90±1.24 mm, MCV was 2.76±1.08 mm, LMV was 2.23±0.51 mm and the PLV was 2.25±0.53 mm. The opening angle of GCV was obtuse in all the cases, MCV drained at an acute angle in 62% subjects and LMV draining angle was acute in 31.33% cases. The valve of the CS was present in 32.7% subjects and absent in 67.3% subjects. The tortuosity was absent in 75.3%. The distance between CS ostium and the ostium of the vein ideal for lead implantation was between 10-40 mm in 76% subjects.Conclusions: The basic knowledge of coronary sinus and its tributaries play a significant role during electrophysiological procedures. The data obtained from the study can be utilised by interventional cardiologist for cannulation of coronary sinus in Kashmiri population.

Association of metabolic risks with subclinical hypothyroidism: a cross-sectional analysis

Objective: To compare lipid parameters, HbA1c, uric acid and albumin creatinine ratio [UACR] among subjects having euthyroidism, Sub-Clinical Hypothyroidism [SCH] and overt hypothyroidism

Methods: This comparative cross-sectional analysis was carried out from Dec-2015 to Oct-2016 in collaboration between PNS HAFEEZ hospital and department of chemical pathology and endocrinology, Armed Forces Institute of Pathology, Rawalpindi. Biochemical parameters including lipid indices, HbA1c and UACR were compared between euthyroidism [TSH: 0.5 to 4.0 mIU/L, n=163], subclinical hypothyroidism [TSH: 4.0 to 10 mIU/L, n=16] and overt hypothyroidism [TSH:>/= 10.0 mIU/L, n=9]

Results: LDL-cholesterol, non-HDL-cholesterol and UACR results were as: [[Euthyroid: 2.66 +/- 0.73], [SCH: 2.68 +/- 0.51] and [Overt hypothyroidism: 3.23 +/- 0.59], p-value=0.063], [[Euthyroid: 3.49 +/- 0.64], [SCH: 3.35 +/- 0.59] and [Overt hypothyroidism: 4.01 +/- 0.30], p-value=0.033] and [[Euthyroid: 2.48 [95% CI: 1.63-3.33]], [SCH: 2.27 [95% CI: 0.37-4.90]] and [Overt hypothyroidism: 14.95 [95% CI: 10.71-19.14]], [p-value< 0.001]]. Results for total cholesterol, triglycerides and HDL-cholesterol though increased in overt hypothyroid group were not found to be statistically significant

Conclusion: LDL-cholesterol, non-HDL-cholesterol and UACR increased from euthyroid subjects to overt hypothyroidism group. However, these changes were found to be more subtle in the subclinical hypothyroid subjects than cases with overt hypothyroidism

Serological monitoring of HCV marker in hemodialysis patients from tertiary care hospitals of Karachi

This study was conducted to estimate the seroprevalence of HCV in maintenance hemodialysis patients. Experimental prospective study. This study had been camed out in the Department of Microbiology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi from 1[st] July, 2010 to 30[th] April, 2011. Irrespective of age and gender 200 samples were collected from the patients on chronic maintenance hemodialysis that at least had 20 cycles of hemodialysis from tertiary care hospital of Karachi. The nature of the sample was 5 cc blood. All the study subjects were briefed about the study program and a written consent form had been signed after getting permission from hospital ethical committee. Diagnosed patients of HCV prior to commencement of hemodialysis and patients who had less than 20 hemodialysis cycles were excluded from this study. Two hundred patients [125 male and 75 females] were between the ages of 30-77 years with mean 56.7 +/- 0.68. 29% patients were seropositive for HCV in chronic maintenance hemodialysis patients. According to duration of dialysis, 3.5% were seropositive in whom duration of dialysis was less than 1 year, 18.4% were seropositive in whom duration of dialysis is in between 1.1-2.0 years, 13.3% were seropositive in whom duration of dialysis is in between 2.1-3.0 years, 52.6% were seropositive in whom duration of dialysis is in between 3.1-4.0 years while 61% were seropositive in whom duration of dialysis is more than 4 years. Highly significant statistical difference is observed as the duration of dialysis increases as p-value is highly significant as 0.001 for HCV. Seroprevalence of HCV infection according to schedule of dialysis is insignificant as the p-value is greater then 0.05. This study confirms that HCV infection is a serious and major problem in our hemodialysis units. Duration of dialysis and surgery is directly proportional to the seropositivity, while transfusion was not statistically related to the cause of HCV infections in hemodialysis patients

Frequency of bacterial, viral and fungal meningitis occurrence in Gadap town Karachi, Pakistan

In the present study the frequency of bacterial [including tuberculous meningitis], viral and fungal meningitis occurrence in Gadap Town, Karachi, Pakistan has been determined. It is a population-based descriptive study which was carried out in Fatima Laboratory Hospital, Baqai Medical University, Karachi from November 2013 to November 2014. A total of 100 cases of meningitis were reported in the hospital during the study period. The physical, chemical and microscopic examinations of the samples were performed following the criteria of the Centers for Disease Control and Prevention [CDC]. In biochemical analysis, glucose was estimated by hexokinase method whereas protein was estimated by calorie method of molybdate. The results of the analysis indicated that the incidence of bacterial meningitis was highest [65%] in the studied population, in which 30% cases were diagnosed with tuberculous meningitis and 35% with other bacterial infections. In the remaining cases, the fungal meningitis [20%] was second most common followed by viral meningitis [15%]

Prevalence of methicillin resistant staphylococcus epidermidis in biomaterial related infections

To determine the prevalence spectrum of methicillin resistant Staphylococcus epidermidis in biomaterial infections. Experimental and observational study. This study was conducted in the department of Microbiology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi, during the period of January 2010 to Dec. 2010. A total of 300 subjects of all ages and sex were included. Swab from cannulae tips, catheters tips, old cannulae infected wounds, injection abscess were collected from Jinnah Postgraduate Medical Centre, National Institute of Child Health and Civil Hospital, Karachi and processed according to standard laboratory methods. A total 103 methicillin resistant Staphylococcus epidermidis, causing biomaterial related infection, isolated from 300 patients were analyzed. Bacterial pathogens were commonly isolated from patients of all ages who developed biomaterial related infections. Patients suffering from infections related with biomaterial should be monitored for MRSE at regular intervals