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Abstract Eukaryotic chromatin is a combination of DNA and histone proteins. It is established fact that epigenetic mechanisms are associated with DNA and histones. Initial studies emphasize on core histones association with DNA, however later studies prove the importance of linker histone H1 epigenetic. There are many types of linker histone H1 found in mammals. These subtypes are cell specific and their amount in different types of cells varies as the cell functions. Many types of post-translational modifications which occur on different residues in each subtype of linker histone H1 induce conformational changes and allow the different subtypes of linker histone H1 to interact with chromatin at different stages during cell cycle which results in the regulation of transcription and gene expression. Proposed O-glycosylation of linker histone H1 promotes condensation of chromatin while phosphorylation of linker histone H1 is known to activate transcription and gene regulation by decondensation of chromatin. Interplay between phosphorylation and O-β-GlcNAc modification on Ser and Thr residues in each subtype of linker histone H1 in Homo sapiens during cell cycle may result in diverse functional regulation of proteins. This in silico study describes the potential phosphorylation, o-glycosylation and their possible interplay sites on conserved Ser/Thr residues in various subtypes of linker histone H1 in Homo sapiens.

Abstract Hepatocellular carcinoma is mainly associated with viral hepatitis B and C. Activation of cell growth stimulator IGF-II gene is observed in tumor formation especially in viral associated hepatocellular carcinoma. Elevated IGF-II levels are indicator of increased risk for cholangiocellular and hepatocellular carcinomas through over saturation of IGF-II binding capacities with IGF receptors leading to cellular dedifferentiation. In HCV, core protein is believed to trans-activate host IGF-II receptor through PKC pathway and the inhibition of tumor cell growth can be achieved by blocking IGF-II pathway either at transcriptional level or increasing its binding with IGFBPs (Insulin like growth factor proteins) at C-terminal, so that it is not available in free form. IGFBP-6 is a specific inhibitor of IGF-II actions. Affinity of IGFBPs with IGFs is controlled by post-translational modifications. Phosphorylation of IGFBPs inhibits IGFs action on target cells while O-glycosylation prevents binding of IGFBP-6 to glycosaminoglycans and cell membranes and resulting in a 10-fold higher affinity for IGF-II. O-glycosylation and phosphorylation operate the functional expression of cellular proteins, this switching on and off the protein expression is difficult to monitor in vivo. By using neural network based prediction methods, we propose that alternate O-β-GlcNAc modification and phosphorylation on Ser 204 control the binding of IGFBP-6 with IGF-II. This information may be used for developing new therapies by regulating IGFBP-6 assembly with IGF-II to minimize the risk of viral associated hepatocellular carcinoma. We can conclude that during HCV/HBV infection, O-β-GlcNAc of IGFBP-6 at Ser 204 diminish their binding with IGF-II, increase IGF-II cellular expression and promote cancer progression which can lead to hepatocellular carcinoma. Furthermore, this site can be used for developing new therapies to control the IGF-II actions during viral infection to minimize the risk of hepatocellular carcinoma.

Objective: To see the common microorganisms infecting diabetic foot ulcers in a tertiary care hospital of Sindh, Pakistan. Study Design: Cross Sectional Descriptive study. Setting: Department of Medicine Civil Hospital, Karachi. Period: June 2023 to November 2023. Methods: It included 102 patients of all ages and gender, who consented to participate and presented with diabetic foot ulcer. Their demographic data and data of isolated microorganism obtained from wound were recorded and analyzed in SPSS version 24. Results: There were 102 patients in our study who visited OPD as case of DFU and consented to take part in study. Mean age was 57.19 ±11.68 Years 24- 90- years patients were included. The highest number of patients 65 (63.7%) were in the 46-65 years age group, followed by the age group of more than 65 years with 21 (20.6%) of the patients. There were 31 (30.4%) females and 71 (69.6%) patients were males. The ratio of male-tofemale participants was 2.2:1. Wagner grade of lesion was 40 (39.2%) were in grade 2 followed by 23 (22.5%) grade Mean age of patients who develop infection in their diabetic foot ulcer i.e. DFI was 56.64 ± 11.62 Years 24- 90- years. Patients were included. The highest number of patients 48 (64.4%) were in the 46-65 years age group, followed by the age group of more than 65 years with 17 (22.7%) of the patients. There were 25 (33.3%) females and 50(66.7%) patients were males. Mean duration of diabetes was 3.83 ±1. Wagner grade of lesion was 27(36%) were in grade 2 followed by grade 3 and 4 which was 18(24%) each. Among the 75 cases from which pathogens were isolated 46(61.3%) were monomicrobial and 29(38.7%) were Polymicrobial. Based on gram staining, 70.67% were gram negative isolates 18.67%were gram positive isolates and 10.67% mixed gram positive and negative isolates. Overall, pseudomonas auraginosa was commonest microbe isolated (41.3%) followed by Klebsiella which is 17.33%. MRSA was commonest among gram positive organism isolated from wound. Conclusion: Diabetic foot ulcers predominantly get infected by Gram negative bacteria. Proper hygienic practices must be encouraged. Appropriate educational programs targeting awareness for diabetes and related complications must be developed to prevent DFU in this cohort of population. [ABSTRACT FROM AUTHOR]

Objective: To determine plasma omentin-1 levels in pregnant females suffering from gestational diabetes mellitus (GDM). Study Design: Case Control study. Setting: Outpatient Department of Obstetrics and Gynecology, Tertiary Care Hospital of Karachi, Pakistan. Period: June 2021 to December 2021. Material & Methods: Ninety-nine gestational diabetic and ninety-six healthy pregnant women were included in this study. A diagnostic criterion for gestational diabetes was oral glucose tolerance test between 24th to 28th weeks of pregnancy. ELISA was performed at KIBGE lab for estimation of plasma omentin-1 levels. Data was analyzed by SPSS software version 22. Results: Mean age of the patients was 30.8±6.4 years. GDM patients had increased body mass index (BMI) (36.0± 6.6vs 32.3 ±4.7; p=0.001), Fasting Blood Glucose (FBG) (110 ±14 vs 77± 9; p=0.001), however, plasma omentin-1levels (4.90±9.01vs 9.56±12.11; p=0.001) were found reduced in GDM as compared to nGDM females. Statistically significant negative correlation was found between plasma omentin-1 and (BMI) (p=0.02). Simple and multi variable regression analysis revealed the statistically significant association of plasma omentin-1 with GDM. Conclusion: Our study has concluded that reduced plasma omentin-1 levels may play a significant role in the development of GDM during pregnancy, so it might be a new possible biomarker for early GDM diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency and pattern of lipid abnormalities in diagnosed female patients of coronary artery disease in a tertiary care hospital of Karachi. Methods: This cross-sectional study was conducted from January 2016 to August 2016. A total of 300 female patients of Coronary Artery Disease (CAD), diagnosed on the basis of angiography were included in the study. For detection of lipid profile abnormalities five ml of fasting venous sample of 10-12 hours was obtained from the left median cubital vein under aseptic conditions. The blood was centrifuged for 5 minutes. Automated chemistry analyzer was used for lipid profile measurement via kits of the CYPRESS Laboratory (Langdorp, Belgium). Statistical analysis was done via SPSS version 17 and results were expressed as percentage and mean ± standard deviation. Results: Mean age of recruited females was 51.36 ± 13.71 years. About 81.39% of patients were found with abnormal lipid profile. The frequency of low high-density lipoprotein cholesterol in studied population was 61.66%, high triglycerides 19.33% whereas; high low-density lipoprotein cholesterol was 17.33% respectively. Combined two parameter dyslipidaemia patterns was found in 41.32% followed by mixed dyslipidaemia in 19.33%, while isolated high-density lipoprotein hypocholesteraemia in 12.00% of study population. Conclusion: We conclude that low levels of high-density lipoprotein cholesterol and hypertriglyceridemia, in both combined and isolated pattern, are more prevalent in Pakistani females with CAD.The data from the current study may increase the knowledge of the guidelines for lipid lowering need in females. [ABSTRACT FROM AUTHOR]

Nocturnal Enuresis (NE) is the involuntary urination during sleep after the age at which bladder control usually occurs. It is a socially stigmatizing and stressful condition which affects around 15%-20% of five years old. Various treatment options for PNE include behavioral therapy, alarm therapy, pharmacotherapy and combinations. Current study was aimed to evaluate outcome of behavioral therapy alone and in combination with pharmacological treatment. OBJECTIVE: To compare the outcome of behavioral therapy alone and in combination with pharmacotherapy in management of NE. OPERATIONAL DEFINITION: Behavioral therapy was performed with prompted voiding (voiding by clock) at day time & reducing fluid intake at bedtime. Pharmacotherapy was performed with orally administered imipramine at bedtime. MATERIAL AND METHOD: STUDY DESIGN: Comparative study. SETTING: Urology department, Children Hospital, Faisalabad. SAMPLING: One hundred & thirty consecutive children in age range of 5-13 years with nocturnal enuresis were enrolled in the study and randomly allocated in two groups. One group was advised behavioral treatment alone and other was advised pharmacotherapy (imipramine) along with behavioral therapy. The children with known urinary tract pathologies/congenital anomalies, active urinary tract infection, acquired urologic disease, neurologic diseases and children with daytime LUTS were excluded from the study. Results: At first follow up (15-days), in group-A (behavioral therapy alone), 7.7% children reported complete resolution of NE, 23.1% showed improvement (reduction in episodes of NE) and 69.2% showed no improvement. At first follow up (15-days), in group-B (combination therapy), 15.4% children reported complete resolution of NE, 61.5% showed improvement (reduction in episodes of NE) and 23.1% showed no improvement. At second follow up (30-days), in group-A (behavioral therapy alone), 38.5% children reported complete resolution of NE, 38.5% showed improvement (reduction in episodes of NE) and 23% showed no improvement. At second follow up (30-days), in group-B (combination therapy), 38.5% children reported complete resolution of NE, 46.2% showed improvement (reduction in episodes of NE) and 15.4% showed no improvement.CONCLUSION: Behavioral therapy can be offered as an initial treatment step in management of nocturnal enuresis. However, combination therapy (behavioral +pharmacotherapy) gives an overall better outcome in the treatment of Nocturnal Enuresis as compared to behavioral therapy alone. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between circulating levels of omentin-1, a novel adipocytokine and coronary artery disease in the local population of Karachi. Methods: A total of 350 subjects were included in the study from June 2016 to December 2016. About 250 patients, who had undergone coronary angiography in Karachi Institute of Heart Disease (KIHD) and Civil Hospital Karachi (CHK) and 100 served as healthy controls. Serum concentrations of omentin-1 were measured by using enzyme-linked immunosorbent assay (ELISA) at Dr. A Q. Khan Institute of Biotechnology (KIBGE) and lipid profile, fasting blood sugar were done at KIHD lab. Coronary artery disease (CAD) and cardiovascular disease risk factors were evaluated by using the software SPSS 16. Independent sample t-test and chi-square tests were used to analyse the clinical and demographic characteristics of data. Simple logistic regression and then multivariate analysis were performed to evaluate correlations between CAD and all other parameters. P value less than 0.05 was considered statistically significant. This research is part of MPhil thesis and there are two research papers; (1) Serum Omentin-1 Levels with CAD (current paper) and (2) genetic polymorphism/mutation of omentin-1 gene in developing CAD. Latter is also in process of publication. Results: Serum omentin-1 levels were found to be lower in patients with CAD as compared to controls (456 ± 99 vs 739 ± 72; p<0.01). Serum concentration of omentin-1 was negatively correlated with body waist circumference (39.95 ± 3.1 vs 30.95 ± 3.7; p< 0.05), whereas positively associated with serum High Density Lipoprotein (HDL) levels (25.9 ± 6.2 vs 42.3 ± 10; p< 0.05). Moreover, multiple logistic regression analysis demonstrated that serum omentin-1 concentration was independently correlated with CAD. Conclusion: The current study has suggested that serum concentrations of omentin-1 might be related to pathogenesis and progress of CAD. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is mainly associated with viral hepatitis B and C. Activation of cell growth stimulator IGF-II gene is observed in tumor formation especially in viral associated hepatocellular carcinoma. Elevated IGF-II levels are indicator of increased risk for cholangiocellular and hepatocellular carcinomas through over saturation of IGF-II binding capacities with IGF receptors leading to cellular dedifferentiation. In HCV, core protein is believed to transactivate host IGF-II receptor through PKC pathway and the inhibition of tumor cell growth can be achieved by blocking IGF-II pathway either at transcriptional level or increasing its binding with IGFBPs (Insulin like growth factor proteins) at C-terminal, so that it is not available in free form. IGFBP-6 is a specific inhibitor of IGF-II actions. Affinity of IGFBPs with IGFs is controlled by post-translational modifications. Phosphorylation of IGFBPs inhibits IGFs action on target cells while O-glycosylation prevents binding of IGFBP-6 to glycosaminoglycans and cell membranes and resulting in a 10-fold higher affinity for IGF-II. O-glycosylation and phosphorylation operate the functional expression of cellular proteins, this switching on and off the protein expression is difficult to monitor in vivo. By using neural network based prediction methods, we propose that alternate O-β-GlcNAc modification and phosphorylation on Ser 204 control the binding of IGFBP-6 with IGF-II. This information may be used for developing new therapies by regulating IGFBP-6 assembly with IGF-II to minimize the risk of viral associated hepatocellular carcinoma. We can conclude that during HCV/HBV infection, O-β-GlcNAc of IGFBP-6 at Ser 204 diminish their binding with IGF-II, increase IGF-II cellular expression and promote cancer progression which can lead to hepatocellular carcinoma. Furthermore, this site can be used for developing new therapies to control the IGF-II actions during viral infection to minimize the risk of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Objective: Chronic disease of the kidney (CKD) is a lethal malady that usually vitiates the function of the kidney. It often stays unrecognized in the earlier stages but over time it may lead to end-stage renal disease (ESRD). CKD is linked to several complications, such as anaemia and infection which can augment the medical complexities. This study aimed to determine the factors leading to severe anaemia in predialysis CKD patients. Methods: A Cross-sectional design was selected to conduct a study in the medicine ward at Abbasi Shaheed Hospital, Karachi from 20/08/23 to 20/08/24. Questions were asked about the duration of the CKD, diabetes mellitus (DM), and hypertension (HTN). A venous sample was collected for investigations including serum urea, creatinine, haemoglobin (Hb), hematocrit (Hct), blood urea nitrogen (BUN)and serum albumin level. Glomerular filtration rate (GFR) was calculated. Stages of CKD were classified as per NKF-K/DOQI classification. The information was entered on proforma and analysed through SPSS-23.0. Results: Among 130 anaemic patients based on haemoglobin, 72 CKD patients had severe anaemia, mean Hb level of 6.59±0.96 g/dl, 49 patients had moderate anaemia with a mean Hb 8.98±0.73 g/dl and only 9 patients had mild type of anaemia, mean Hb 11.96±0.60 g/dl with significant p-value. (p-value=0.000) GFR was 12.00±6.94 ml/min/1.73m2 in patients having severe anaemia, 17.20±9.82 ml/min/1.73m2.in in individuals having moderate anaemia and 18.79±10.22 ml/min/1.73m2 in CKD patients having mild anaemia. (p-value=0.001) Conclusion: The severity of anaemia in advanced stages of CKD is a striking observation. There is a need for early diagnosis and management of kidney disease and nevertheless routine monitoring of kidney function especially in diabetic and hypertensive patients. [ABSTRACT FROM AUTHOR]

Objectives: To determine the levels of zinc in hair and serum samples of chronic telogen effluvium patients., Methods: The case-control study was conducted at the Dow University of Health Sciences, Karachi, from April 2017 to May 2018, and comprised diagnosed cases of chronic telogen effluvium in group A, and healthy controls matched for age and gender in group B. Hair pull test was done, and level of zinc in hair and serum samples was determined using atomic absorption spectrophotometer. Data was analysed using SPSS 21., Results: Of the 100 subjects, 50(50%) were in group A; 28(56%) females ad 22(44%) males with mean age 27.46±4.98 years. There were 50(50%) subejcts in group B; 26(52%) males ad 24(48%) females with mean age 28.34±4.92 years (p>0.05). Significantly low levels of zinc were observed in serum as well as hair samples in group A compared to group B (p<0.05). A positive significant association was observed in the level of zinc in hair with their concentration in the serum of subjects in both the groups (r=0.310, p<0.05)., Conclusions: Low levels of zinc in hair and serum were found to be associated with chronic telogen effluvium.

Objective: To investigate the correlation of Adenine-1012-Guanine (rs4516035) promoter region polymorphism of vitamin-D receptor gene with serum levels of omentin-1, vitamin-D and vitamin-D receptor protein in patients with coronary artery disease., Methods: The case-control study was conducted from January to June 2020 at the cardiac unit of Civil hospital Karachi (CHK), and comprised coronary artery disease patients and controls. The tetra-primer amplification refractory mutation system polymerase chain reaction method was used to genotype Adenine-1210Guanine polymorphism in the vitamin D receptor gene. Serum levels of omentin-1, vitamin-D, and vitamin-D receptor protein were measured in both the groups using an enzyme-linked immunosorbent assay. Data was analysed using SPSS 17., Results: Of the 1,000 subjects, there were 500(50%) cases; males 306(61.2%) and 194(38.8%) females with overall mean age of 51.08±9.55 years. The remaining 500(50%) were controls; 290(58%) males and 210(42%) females with overall mean age of 50.9±10.78 years. The mutant Guanine allele was more prevalent in controls 261(52.2%), and had a non-significant correlation with coronary artery disease (p=0.45). Among the cases, the wild Adenine-Adenine genotype had a higher prevalence 402(80.4%) and had a significant correlation with coronary artery disease (p<0.001). The heterozygous genotype Adenine-Guanine was significantly more predominant among the controls 346(69.2%) compared to the cases 66(13.2) (p=0.002)., Conclusions: Adenine-1012-Guanine polymorphism in the vitamin-D receptor gene was found to be a protective polymorphism for coronary artery disease in the recessive model.

Background & Objective: Coronary artery disease (CAD) is a most important cause of morbidity and mortality worldwide as well as in Pakistan. Recent studies have shown that the combination of obesity, insulin resistance and fluctuation in circulating adipocytokines levels is associated with the pathogenesis of coronary artery disease. Omentin-1 is recently found adipocytokine that is highly expressed in visceral adipose tissue. It has anti- inflammatory properties and is negatively correlated with ischemic heart disease. Therefore, this study was designed to investigate the relationship between omentin-1 Val109Asp polymorphism and CAD in Pakistani population., Methods: A total of 350 subjects were included in the study. Two hundred fifty were diagnosed with coronary artery disease while 100 served as healthy controls. PCR-RFLP was performed at Dr. A Q. Khan Institute of Biotechnology (KIBGE) to analyze Val109Asp polymorphism. In this, case control study SPSS software version 16 (Chicago, IL, USA) was used for data analysis. Continuous variables and categorical variables were presented as mean±SD or in percentage. Independent sample test and chi-square test was performed to compare the differences in means between cases and controls. Genotype distribution was analyzed by chi-square test and results were presented as percentage and frequency. Multivarible regression analysis indicated that Val109Asp SNP might be an independent risk factor for CAD susceptibility after adjustment for some well- known CAD risk factors including age, gender, body mass index, smoking, hypertension, diabetes mellitus and lipid abnormalities. There was estimation of odd ratios (OR) and 95% confidence intervals (CIs) to determine the correlation between genotypes and the risk of CAD. (p> 0.05). Genotype frequencies were compared by Chi-square test., Results: There was prevalence of Omentin-1 Val109Asp polymorphism in both case and control groups. However, Val/Asp (heterozygous mutant) genotype was detected more frequently in patients with CAD, OR(95%)=1.921; CI=1.173-3.1469 in comparison of Asp/Asp and Val/Val genotypes., Conclusion: Individuals having Val/Asp heterozygous gemotype of omentin-1 gene polymorphism are at more risk of developing CAD in Pakistani population, further studies are required in different populations and ethnicities to confirm our findings.