Demographic analysis of hearing impairment based on various parameters in patients with cochlear implant.

Objectives: To analyse the demographic and clinical variables in children having undergone cochlear implant surgery because of deafness. METHODS: The cross-sectional study was conducted from January to November 2022 at the Centre for Research in Experimental and Applied Medicine laboratory of the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Ear, Nose and Throat Department of Combined Military Hospital, Rawalpindi, and comprised children of eith gender aged up to 10 years who had received cochlear implant. Data was collected through questionnaire-based detailed interviews. Syndromic Hearing Loss, Non-Syndromic Hearing Loss, and Acquired Hearing Loss were identified among the subjects. Data was analysed using SPSS 22. RESULTS: Of the 250 cases, 147(58.8%) were boys, 146(58.4%) were aged 0-5 years, 219(87.6%) had prelingual onset of disease, and 202(80.8%) had a non-progressive disease course. In 203(81.2%) cases, normal developmental milestones were seen. Parental consanguinity was observed in 219(87.6%) cases. However, 63(25.2%) patients had a first-degree relative who had a history of deafness. In 170(68%) cases, hearing loss was hereditary, whereas in 80(32%) it was acquired. Meningitis was the most commonly identified risk factor 55(68.75%). Acquired risk factors and family history had significant association with hearing loss (p<0.05). Speech perception significantly improved in all 219(100%) patients with prelingual hearing loss who underwent cochlear implantation. CONCLUSIONS: Majority of the cases were found to be male, had a prelingual disease onset and a non-progressive disease course. Family history was a significant factor, while meningitis was the most common acquired cause of hearing loss.

Determination of Glyoxalase-1 levels and Identification of Genetic Variants in GLO1 Gene in Patients of Diabetic Nephropathy.

Objective: To determine the association of diabetic nephropathy with glyoxalase-1 enzyme levels and a genetic missense variation (SNP rs4746) in its gene (GLO-1). Methods: This cross-sectional comparative study was conducted at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi from November 2020 to December 2022. One hundred patients and one hundred and thirteen healthy controls were enrolled using the nonprobability convenience sampling method. Medical history and 10ml blood were obtained from each individual after written informed consent. Blood samples were subjected to biochemical tests and DNA extraction which was later used for single nucleotide polymorphism (SNP) analysis (C332C variant of rs4741 GLO-1 gene) using Tetra primer ARMS PCR and gel electrophoresis. Glyoxalase-1 enzyme activity in serum was measured using ELISA. Results: There was a significant difference in serum glyoxalase-1 levels in the two groups (p-value< 0.001). The patient group had lower levels (16.24 ± 22.51mg/dl) of glyoxalase-1 as compared to the control group (48.70 ± 42.54mg/dl). In genotypic analysis, 98 out of 100 control individuals had AA genotype-while only one had CC and another AC genotype. In the patient group, 94 out of 100 patients showed AA genotype, three AC, and three CC genotypes. As the statistical significance (p-value) was 0.37, there was no significant association found between AC or CC genotype and diabetic nephropathy. Conclusion: Glyoxalase-1 levels are linked to the development of diabetic nephropathy in our patients while a known missense variant rs4746 in the GLO-1 gene is not associated with increased risk.

Association of serum IL12 with clinical and biochemical parameters in a cohort of diagnosed rheumatoid arthritis patients on oral conventional synthetic disease modifying anti-rheumatic drugs.

Objective: To determine the association of serum interleukin-12 levels with disease progression in active rheumatoid arthritis patients on oral conventional synthetic disease-modifying anti-rheumatic drugs. METHODS: The case-control study was conducted at the Army Medical College, Rawalpindi, in collaboration with the Pak Emirates Military Hospital, Rawalpindi, Pakistan, from January to December 2022, and comprised rheumatoid arthritis patients or either gender aged 18-75 years who were placed in group I, while group II comprised healthy controls. Demographic and clinical data was noted, and 2ml blood samples were drawn from each subject. The serum was separated and analysed using sandwich enzyme-linked immunosorbent assay to quantify serum interleukin-12 levels. Data was analysed using SPSS 22. RESULTS: Of the 150 subjects, 75(50%) were in group I; 27(36%) males and 48(64%) females with overall mean age 45.70±11.70 years. There were 75(50%) subjects in group II; 37(49.3%) males and 38(50.7%) females with overall mean age 31.70±7.70 years. Serum interleukin-12, erythrocyte sedimentation rate and C-reactive proteinquantitative levels were significantly higher in group I compared to group II (p<0.05). Smoking, positive family history of rheumatoid arthritis in a first-degree relative and history of consanguinity were identified as risk factors though they were not statistically significant (p>0.05). In group I (n=75), out of total study subjects, only 55(73.3%) cases belonged to the predominant castes, namely Awan, Rajput, Pathan, Araeen, Bhatti, Malik, Mughal, Sudhan, Chaudary, and Jutt. These individuals showed significantly higher mean serum interleukin-12 levels compared to patients of other castes in the same group. Conclusion: Mean serum interleukin-12 levels were higher in rheumatoid arthritis patients despite being on oral conventional synthetic disease-modifying anti-rheumatic drugs.

An insight into genetic landscape of inflammatory bowel disease.

Inflammatory bowel disease has been regarded to be chronic intestinal inflammation characterised by a dsyregulatory immune response. The disease pathophysiology is known to be complex. Growing pieces of evidences underpin the involvement of various environmental and genetic determinants in the disease onset. The current narrative review was planned to manifest the contribution of genetic drivers for disease onset and to target signalling pathways that might present a therapeutic potential for further research. The factors of the disease that provide the genetic nature and understanding of the pathways involved have been researched in recent times. Also, numerous diseasedeveloping factors have been studied and assessed. Among them genetic determinants of disease onset have further improved the understanding of disease development. Genetic contributors to the onset of disease as well as important therapeutic targets need to be understood as predictive genetic risk factors have a potential implication for personalised treatment.

Expression analysis of ABCA1 in type 2 diabetic Pakistani patients with and without dyslipidemia and correlation with glycemic index and lipid profile.

Diabetes Mellitus type II, earlier considered as an endocrinological disorder is now more regarded as an inflammatory disorder along with lipid aberrations. It demands for regular monitoring, healthy dietary habits and lifestyle modification. This study was focused on gene expression of ATP binding cassette protein 1 (ABCA1) in diabetic dyslipidemia patients in comparison with control groups of only diabetics and healthy individuals. Blood samples and data were collected from recruited 390 patients who were further divided into three groups (130 each). Glycemic index and lipid profile was assessed. Delta Delta Ct method was used that revealed downregulation of the studied gene more in diabetic dyslipidemia patients as compared to only diabetics and healthy controls. The Ct values of ABCA1 were associated with glycemic index and lipid profile using Pearson's correlation. A negative correlation with fasting blood sugar and a positive correlation with HbA1cwas observed in only diabetics group. While in diabetic dyslipidemia and normal healthy controls, a negative correlation was found with both. As far as the lipid profile is concerned a positive correlation was observed among only diabetics with whole lipid profile. In diabetics with dyslipidemia, a negative correlation with all parameters except the TAGs was observed. A positive correlation with all except HDL was observed in healthy controls. The Ct values and fold change were compared among diseased and healthy individuals by applying independent t test. The cycle threshold in only diabetics was p = 0.000018 and in diabetic dyslipdemia individuals was p = 0.00251 while fold change in only diabetics (p = 0.000230) and in diabetics with dyslipidemia (p = 0.001137) was observed to be as statistically significant.

Association of R1939W and P1987R variants of Otoferlin (OTOF) gene with severe to profound nonsyndromic sensorineural hearing loss in Pakistani subjects.

Objective: To find possible association of R1939W and P1987R variants of OTOF gene with severe to profound NSSHL in cochlear implant subjects. Methods: It was a case control study, conducted from June 2021 to February 2022, comprising 50 cases of severe to profound NSSHL who had received cochlear implant from ENT Department, CMH Rawalpindi and 50 age-matched healthy controls from PEMH Rawalpindi. Blood samples were collected from all the subjects, followed by DNA extraction and allele-specific polymerase chain reaction, performed at Multi-disciplinary Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi. Statistical analysis was done using 'SPSS' and 'XLSTAT', followed by genetic analysis using 'SNPstat'. Results: Mean age of the cases was 5.96 ± 4.62 years (N=50), comprising 58% males and 42% females. All had bilateral and prelingual HL. Parental consanguinity was 72%, whereas 62% cases had a positive family history of deafness. Alleles of R1939W and P1987R were not associated with NSSHL, as shown by their p values of 0.56 and 0.89 respectively. For R1939W ORs were 0.71 (dominant model) and 0.80 (overdominant model), indicating negative association with NSSHL. Regarding P1987R OR was 0.96 (log-additive model). Genotypes of both variants were not in HW Equilibrium (p <0.0001), whereas their alleles showed high LD (D'=0.92). Conclusion: High percentage of parental consanguinity was observed among cochlear implant candidates. The OTOF variants R1939W and P1987R were found to have protective roles against NSSHL in study population.

Identification and Association of Polymorphism rs2073618 of the Osteoprotegerin Gene in Type 2 Diabetics with and without Retinopathy.

OBJECTIVE: To identify and determine the association of SNP (rs2073618) of OPG gene in diabetics with and without retinopathy and in healthy controls. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi in collaboration with Chemical Pathology Laboratory, Pak Emirates Military Hospital, Rawalpindi and Armed Forces Institute of Ophthalmology, Rawalpindi, from June 2021 to May 2022. METHODOLOGY: Participants aged 25-70 years were inducted and divided into three equal groups. Group I consisted of diabetics with retinopathy (n = 50), group II was diabetics without retinopathy (n = 50), and group III was healthy individuals (n = 50). DNA was extracted and allele specific PCR technique was adopted using specifically designed primers. Results were analysed using the software Statistical Package for Social Sciences (SPSS) version 22.0 and online bio-informatics tool SNPstats. RESULTS: CC, CG, and GG genotypes were found to be present in 94%, 4%, and 2% in diabetics without retinopathy, 92%, 4%, and 4% in diabetics with retinopathy, respectively, and 100% presence of CC genotype only in healthy controls. C and G alleles were present in 96% and 4%, respectively, in diabetics without retinopathy, with 100% presence of only C allele in healthy subjects. The genotypic assessment using the models showed no significant association. CONCLUSION: SNP rs2073618 of OPG gene was identified in all study groups without any significant distribution or association with the development of diabetic retinopathy. The major genotype C/C was found in the majority of subjects in all groups. KEY WORDS: Allele specific PCR, Diabetic retinopathy, Single nucleotide polymorphism, Type 2 Diabetes mellitus.

Aldose reductase gene polymorphism rs752010122 and retinopathy in type 2 diabetics.

Objectives: To investigate the association of polymorphism in rs752010122 in aldose reductase gene with the pathogenesis of diabetic retinopathy, and to determine the association and allelic frequency between the variant and the disease. METHODS: The cross-sectional study was conducted from June 2021 to March 2022 at Centre for Research in Experimental and Applied Medicine (CREAM) Laboratory, Department of Biochemistry and Molecular Biology, Army Medical College, in collaboration with the Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan, and comprised blood samples from subjects of either gender aged 40-70 years. The samples were divided into group I having diabetic retinopathy patients, group II having diabetics without retinopathy, and group III having healthy controls matched for age and gender. The samples were subjected to molecular analysis. Gene sequence was downloaded from the Human Genome Database and Ensemble. Data was analysed using SPSS 22. RESULTS: Of the 150 subjects, there were 50(33.3%) in each of the 3 groups. Variants of aldose reductase rs752010122 polymorphism were significantly associated with a lower risk of diabetic retinopathy (p<0.05). An odds ratio of 1 was noted for both heterozygous and homozygous genotypes (95% confidence interval: 1). CONCLUSIONS: Aldose reductase was associated with lower risk of the disease.

Risk Analysis and Assessment of Lipid Abnormalities as the Earliest Complication in Newly Diagnosed Diabetic and Non-Diabetic Individuals of a Local Population.

Lipid variations have been frequently observed in global populations that can affect health status. Mainly studies have been conducted on the type 2 diabetic population, but limited data is available on newly diagnosed ones to unravel complications and risk predictors independent of disease progression. This study comprising 244 individuals was carried out to assess the lipid abnormalities in newly diagnosed diabetics and non-diabetics. The clinical and socio-demographic data were collected and analyzed using independent samples t-test and linear regression. Serum lipid variations were observed individually and in combination. The individuals in group I (diabetics with dyslipidemia) revealed elevated levels of low-density lipoprotein and serum triglycerides higher than in group II (non-diabetics with dyslipidemia). The frequency of deranged total cholesterol in group I was observed to be higher than in group II. Independent samples t-test showed a significant mean difference in variables between the two groups. Linear regression analysis showed a significant variable outcome for predictors between high-density lipoprotein (HDL) and physical activity (B= -0.043, 95% CI: -0.80, -0.006) and total cholesterol (TC) with family history (B= -0.062, 95% CI: -0.123, -0.001). The findings conclude that lipid levels deranged independently regardless of type 2 diabetes mellitus and present as an early onset in type 2 diabetes instead of later stage complication. These derangements of lipid levels are an independent risk factor for future cardiovascular pathology.

Peroxisome Proliferator-Activated Receptor-α (PPARα) Expression in a Clinical Population of Pakistani Patients with Type 2 Diabetes and Dyslipidemia.

Poor glycemic control and dyslipidemia are hallmarks of type 2 diabetes mellitus (T2DM), which predispose to cardiovascular diseases. Peroxisome proliferator-activated receptor-α (PPARα) has been associated with atherosclerosis, but its role in T2DM is less clear. Previously, we studied PPARα expression levels in diabetics with and without dyslipidemia (DD). In this study we described the association with fasting blood glucose, HbA1c levels and lipid levels of the study population. Patient demography and biochemical data were collected from hospitals in Islamabad, Pakistan, and RT-PCR data of PPARα expression were retrieved from our previous study from the same cohort. We performed t-tests and regression analysis to evaluate the relationships between PPARα expression and demographic and clinical variables. As expected, body mass index and HbA1c were elevated in T2DM and DD patients compared to controls. Blood lipids (total cholesterol, triglycerides, LDL and HDL) were significantly higher in the DD group compared to the other two groups. In the T2DM and DD groups, the PPARα expression was not associated with any of the physical and biochemical parameters measured in this study. Expression of the PPARα gene was independent of blood lipids and glycemic control in this study. Further research is necessary to better understand the biological parameters of PPARα expression.

Determination of Pleiotropic Effect of Warfarin in VKORC1 and CYP2C9 Genotypes in Patients With Heart Valve Replacement.

Warfarin has been widely used as an oral anticoagulant agent. In past, efforts have been done to study the contribution of genetic variation on warfarin dose requirements. The possible therapeutic dose determination of warfarin is very challenging, i.e., extremely low dose leading to unusable antithrombotic therapy or high dose causes particularly bleeding complications. Our study aimed to investigate these observations in more detail, we determined the correlation of interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) among VKORC1 and CYP2C9 genetic variants in patients with heart valve replacement who were treated with a range of warfarin doses and compared with levels in healthy controls. A total of 107 human subjects were recruited with low < 5 mg, medium 5-10 mg/day, and high > 10 mg/day warfarin doses. The genetic study of VKORC1-1639G/A, C1173T, 3730G > A, CYP2C9*2, and CYP2C9*3 was performed using TaqMan genotyping and DNA sequencing. The gene expression of IL-6, TNF-α, and COX-2 mRNA was analyzed. IL-6, TNF-α, and COX-2 protein expressions were determined by ELISA and Western blot analysis to evaluate the pro- and anti-inflammatory effects of warfarin. A statistically significant difference was found among the haplotypes of VKORC1 rs9934438 (C1173T), rs9923231 (-1639G > A), rs7294 (3730G > A) and CYP2C9 *2 p. Arg144 Cys (rs28371674), CYP2C9 *3 p. Ile359Leu (rs1057910) genotypes with warfarin dose requirements (p = 0.001). The increased levels of COX-2, IL-6, and TNF-α proteins were observed when a high dose of warfarin (>10 mg/ml) was administered. However, a lower concentration (1.0 mg/ml) was observed with decreased warfarin dose (<5 mg/day). The present study reported that in addition to its anticoagulant action, the genetic variants of warfarin may have a pleiotropic effect by influencing IL-6 depending on the dosing regimen and inducing the expression of COX-2.

Osteogenic Induction with Silicon Hydroxyapatite Using Modified Autologous Adipose Tissue-Derived Stromal Vascular Fraction: In Vitro and Qualitative Histomorphometric Analysis.

Large bone defects requiring invasive surgical procedures have long been a problem for orthopedic surgeons. Despite the use of autologous bone grafting, satisfactory results are often not achieved due to associated limitations. Biomaterials are viable alternatives and have lately been used in association with Stromal Vascular Fraction (SVF), stem cells, and signaling factors for bone tissue engineering (BTE). The objective of the current study was to assess the biocompatibility of Silicon Hydroxyapatite (Si-HA) and to improve osteogenic potential by using autologous adipose-derived SVF with Si-HA in a rabbit bone defect model. Si-HA granules synthesized using a wet precipitation method were used. They were characterized using scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). A hemolysis assay was used to assess the hemolytic effects of Si-HA, while cell viability was assessed through Alamar Blue assay using MC3T3 mouse osteoblasts. The osteogenic potential of Si-HA both alone and with enzymatically/non-enzymatically-derived SVF (modified) was performed by implantation in a rabbit tibia model followed by histomorphometric analysis and SEM of dissected bone after six weeks. The results showed that Si-HA granules were microporous and phase pure and that the addition of Silicon did not influence Si-HA phase composition. Si-HA granules were found to be non-hemolytic on the hemolysis assay and non-toxic to MC3T3 mouse osteoblasts on the Alamar Blue assay. Six weeks following implantation Si-HA showed high biocompatibility, with increased bone formation in all groups compared to control. Histologically more mature bone was formed in the Si-HA implanted along with non-enzymatically-derived modified SVF. Bone formation was observed on and around Si-HA, reflecting osseointegration. In conclusion, Si-HA is osteoconductive and promotes osteogenesis, and its use with SVF enhances osteogenesis.

Association of C-262 polymorphism in catalase gene with rheumatoid arthritis.

OBJECTIVE: To evaluate the association of C-262 polymorphism in Catalase gene (CAT) with Rheumatoid Arthritis. METHODS: The comparative cross-sectional study was conducted at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, in collaboration with the Rheumatology Department, Pak Emirates Military Hospital, Rawalpindi, Pakistan, from January to December 2020, and comprised Deoxyribonucleic acid extraction of samples. Samples in group I belonged to diagnosed rheumatoid arthritis patients of either gender aged 30-60 years who were on disease-modifying anti-rheumatic drugs. Group II had an equal number of healthy controls. The promoter region of the CAT gene having the polymorphic segment was amplified through polymerase chain reaction, and its products were then subjected to restriction fragment length polymorphism for the analysis of polymorphic region of the CAT gene. Genotypic frequency equilibrium and the association of polymorphism with rheumatoid arthritis was checked. Also, association between fasting lipid profile and haemoglobin was assessed. Data was analysed using SPSSS 22. RESULTS: Of the 60 samples, 30(50%) belonged to each of the two groups. The mean age was 44.90±10.50 years (range: 30-60 years). Overall, there were 34(56.7%) males and 26(43.3%) were females. Two alleles and three genotypes of the polymorphism was detected. The frequency of CC genotype was higher in group I 23(76.6%), but no association of any of the genotype of polymorphism was found significant (p <0.05). Haemoglobin and lipid profile levels were significantly different in the two groups (p≤0.05). CONCLUSIONS: There was no significant association found between C-262 polymorphism in CAT gene and rheumatoid arthritis.

A Comparative Analysis of Superoxide Dismutase 1 Level in Diabetics with and without Neuropathy.

OBJECTIVE: To compare superoxide dismutase 1 (SOD1) levels in diabetes mellitus patients with and without neuropathy. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: Multidisciplinary Lab-1 of the Department of Biochemistry and Molecular Biology, Army Medical College, in cooperation with Pak-Emirates Military Hospital, Rawalpindi, Pakistan, from January 2020 to January 2021. METHODOLOGY: Eighty-four subjects were enrolled through non-probability purposive sampling technique. They were further divided into three groups. Patients with diabetic neuropathy were labelled as the group Ι, and patients with diabetes mellitus without neuropathy were included in group ΙΙ. While group ΙΙΙ was comprised of healthy individuals and taken as control. Biochemical parameters included fasting blood glucose levels and HbA1c. Superoxide dismutase-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Data were evaluated by SPSS version 22.0 and presented in percentage and mean ± standard deviation (SD). Independent sample t-test and one-way ANOVA followed by the post-hoc Tukey test were used for group comparison. RESULTS: Mean level of SOD1 was significantly higher in group Ι as compared to group ΙΙ and ΙΙΙ (p<0.001). Statistically significant difference was observed among groups Ι and ΙΙ (p=0.002), Ι and ΙΙΙ (p<0.001), and ΙΙ and ΙΙΙ (p=0.017). Mean levels of SOD1 were also significantly increased with poor glycemic control (p<0.001). CONCLUSION: SOD1 level was considerably high in patients with diabetes mellitus with neuropathy in comparison to diabetics without neuropathy and healthy individuals. Key Words: Diabetes mellitus, Diabetic neuropathy, ELISA, Superoxide dismutase 1(SOD1).

Association of Pro198Leu polymorphism in glutathione peroxidase one (GPX1) gene with peripheral neuropathy in type 2 diabetic patients.

OBJECTIVE: To evaluate the association of Pro198Leu polymorphism in glutathione peroxidase 1 gene in type 2 diabetic patients with neuropathy. METHODS: The comparative cross-sectional study was conducted from February 2 to November 30, 2018, at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Department of Neurology, Military Hospital, Rawalpindi. Diagnosed type 2 diabetics of either genders aged 40-70 years were divided into two equal groups of neuropathy and non- neuropathy subjects. Deoxyribonucleic acid was subjected to restriction fragment length polymorphism for glutathione peroxidase 1gene analysis. Hardy Weinberg equation was used to check the genotype frequency equilibrium. RESULTS: Of the 60 patients, there were 30(50%) each in the two groups. Age, fasting glucose level and diabetes duration were significantly different between the groups (p<0.05). Even though the frequency of TT genotype was higher, no association of the polymorphism and any of the genotypes was found with diabetic neuropathy (p>0.05). CONCLUSIONS: There was no association found between Pro198 Lue polymorphism in glutathione peroxidase 1 and diabetic neuropathy.

Perifollicular Vascularity in Poor Ovarian Responders in In vitro Fertilization Cycles.

CONTEXT: Poor response is reported in 9%-24% of stimulated cycles. Color Doppler indices of follicular blood flow are correlated with oocyte recovery, fertilization rate, developmental potential of oocyte, and pregnancy rate in in vitro fertilization (IVF) treatment. AIM: The aim of this study is to find out the correlation between perifollicular vascularity with clinical outcomes in poor ovarian responders during IVF cycles. SETTINGS AND DESIGN: A total of 49 poor ovarian responder women undergoing conventional IVF-embryo transfer procedure at a tertiary care hospital between September 2014 and 2015 were included in the study. It was a prospective observational study. SUBJECTS AND METHODS: Patients were recruited on the day of trigger following a transvaginal ultrasound if they developed ≤4 dominant follicles of ≥16 mm diameter. After ovarian stimulation patients who had all follicles with low-grade vascularity were classified as Group A, those with follicles with high-grade vascularity were Group C, and Group B included patients with follicles of both good and poor vascularity. STATISTICAL ANALYSIS USED: Analysis of variance and Chi-square/Fisher's exact test and software, namely SAS 9.2 and SPSS 15, has been used. RESULTS: A total 49 patients were recruited for the study.10 patients were allocated in Group A, 26 patients in Group B and 13 in Group C. Both groups were comparable in terms of age, period of infertility, follicle-stimulating hormone, luteinizing hormone, and gonadotrophin requirement. The number of metaphase II oocytes and good quality oocytes was significantly higher in Group C. Implantation rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, and live birth rate were comparable among all groups. CONCLUSIONS: Perifollicular vascularity has an important role to play in clinical outcomes in poor ovarian responders in IVF cycles.

Correlation between Genotoxicity and Interleukin-6 in Smokers: A Rodent Model.

OBJECTIVE: To investigate the relation between genotoxicity and interleukin-6 in rats exposed to cigarette smoke. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Army Medical College, Rawalpindi and Armed Forces Institute of Pathology, Rawalpindi, in 2016. METHODOLOGY: Seventy healthy Sprague Dawley rats were placed in smoke chambers at animal house of National Institute of Health, Islamabad. Cigarette smoke was given to them for 3 months. Genotoxicity was assessed by CytokinesisBlock Micronucleus (CBMN) assay. Enzyme linked immunosorbent assay (ELISA) kit was used to determine Interleukin-6 in study samples. Pearson correlation was used to find the correlation between genotoxicity and IL-6. RESULTS: The mean IL-6 and micronuclei frequency was 49.48 ±19.69 ng/L and 6.77 ±0.73, respectively. Weak positive association was found between micronuclei frequency and IL-6 in smoke exposed rats (r=0.266, N=70, p=0.026). CONCLUSION: Genotoxicity and inflammation are associated in smokers. The present study concluded that smoke exposure elicited a proinflammatory profile, which might have promoted DNA damage in smokers.

Evaluation of correlation between expression of P53 and Malondialdehyde levels in prostate cancer patients.

The analytical study was conducted at the National University of Sciences and Technology, Islamabad, Pakistan from Nov 2012 to Nov 2013 to find out, correlate and assess negative correlation of serum malondialdehyde (MDA) with expression of p53 gene, and comprised 32 samples. Expression of p53 and MDA levels were determined by real time quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) technique respectively. Mean value of MDA in prostate carcinoma (CaP) and control group were compared, and the difference was statistically significant (p=0.002). Mean cycle threshold (CT) value of CaP was compared with control group, and the difference was statistically significant (p<0.05). Expression of p53 was 0.18 folds decreased in CaP compared to control group. MDA may be used as marker to determine prognosis of CaP. Expression of p53 may be helpful in the diagnosis of CaP.

Report-Model studies of transmembrane interaction of FcεRIα/FcRγ reveal novel strategies to inhibit allergic responses.

The high-affinity IgE receptor complex plays an essential part in allergic responses and involved in downstream signaling, released inflammatory mediators that cause allergic responses. The transmembrane region of the high-affinity IgE has a conserved motif (LFAVDTGL) where a polar aspartate (D194) is important for the ligand binding. This modeling study proposes novel potential binding sites between high affinity immunoglobulin E receptor α subunit (FcεRIα) and FcRγ and as a consequence, we propose a new model of FcεRIα and FcRγ interaction (T194) which can mediate downstream signaling in allergic response. The docking of FcRγ with wild-type (D194) and mutant human high affinity immunoglobulin E receptor α subunit (D194T, D194I, D194L, D194A, D194V, D194E, D194S and D194R) has been performed on Autodock Vina. This modeling study is based on lab data obtained by carrying out site-directed mutagenesis done at residue D194 of FcεRIα to assess its functional importance for the mediation of intracellular signal cascade. HuFcεRIα D194 residue was replaced with threonine, leucine, serine, arginine, alanine, asparagine and glutamic acid. FcRγ docking on mutated huFcεRIα (D194T) indicated a new site of interaction and emphasizes the significance of the charge and size of an amino acid at position 194 in huFcεRIα subunit. Amino acids D & T at position 194 are important for cell surface localization, interactions, distribution and downstream signaling of IgE receptor subunit. These proposed models may herald in better therapeutic interventions to combat unfavorably allergic diseases.