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Introduction: The prognosis of Guillain-Barré Syndrome (GBS) at an early stage with explicit biomarkers is critical to distinguish patients with possibility of poor recovery. Cerebrospinal fluid (CSF) serves as an impending source for biomarkers that portrays the exact biochemical changes. Aim: To find out if there is any prognostic value of high CSF phosphorylated Neurofilament Heavy subunit (pNf-H) levels, measured during first two weeks of onset of GBS, as assessed by the level of disability at six months after the onset of GBS. Materials and Methods: The cohort study was conducted in the Department of Neurology and Department of Immunology and Molecular Medicine, at the Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India, over a period of two years from August 2015 to August 2017. Sixty two patients who satisfied the required diagnostic standards for GBS (study group) and 35 patients with tensiontype headache (control group) were selected for the study. After clinical and electrophysiological assessment, CSF samples were collected. A commercially available sandwich enzyme immunoassay kit, manufactured by BioVendor-Laboratorní medicína (Czech Republic), was used for measuring human pNf-H quantitatively. Results: Mean CSF pNf-H level in patients with good outcome was 325.3 pg/mL whereas, in patients with poor outcome it was 3655.2 pg/mL. CSF pNf-H levels were found to be suggestively higher in GBS patients with poor outcome as compared to those with good outcome. Only eight patients in good outcome group had pathologically high CSF Nf-H levels whereas 10 patients in poor outcome group had CSF Nf-H levels ≤730 pg/mL. The odds ratio was 17.1 (95% Confidence Interval (CI) 3.83-76.29). Thus, high CSF Nf-H levels on admission predicted poor outcome in GBS (p-value <0.001). Moderate degree of positive correlation was found between CSF Nf-H levels and outcome (F score) at six months (R=0.684; p-value <0.001). Conclusion: It can be determined that higher values of CSF pNf-H in GBS (acute stage), could serve as a predictive marker indicative of poor prognosis. [ABSTRACT FROM AUTHOR]

Aim: Data about polymorphism in tumor necrosis factor alpha (TNF-α) and its serum levels in chronic obstructive pulmonary disease (COPD) are conflicting. We aimed to evaluate the association of TNF-α 308 G > A polymorphism in patients with COPD in Kashmir (North India), a high burden area and also determined the serum TNF-αlevels in these patients. Materials and Methods: One hundred spirometrically confirmed COPD patients and 163 controls resident from Kashmir valley (North India) were recruited. Genotyping of the promoter region of TNF-α was carried out using polymerase chain reaction restriction fragment length polymorphism. The serum TNF-αwas quantified using the Cytometric Bead Array flex system by flow cytometry. Results were subjected to appropriate statistical treatment and P < 0.05 was considered statistically significant. Results: Ninety one COPD patients (91%) had G/G (wild homozygous) genotype and nine patients (9%) had G/A (heterozygous) genotype. Among the control population, 150 (92%) had G/G genotype and 13 (8%) had G/A genotype. The variant allele "A" was not detected in either of the two groups. Serum levels of TNF- αwere significantly higher in patients compared to control group (8.0 ± 10.1 pg/ml vs. 3.3 ± 0.42 pg/ml, respectively, P = 0.0001). Conclusion: While serum levels of TNF-α are higher in COPD patients compared to the controls, there was no difference in the prevalence of TNF-α 308 polymorphism in the ethnic Kashmiri population with COPD. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is characterized by an interaction of various environmental influences especially cigarette smoking and genetic determinants. The prevalence of this disease is ever increasing and characterization of the genetic determinants of the disease has been undertaken globally. The 'A disintegrin and metalloprotease 33' (ADAM 33) gene is one candidate gene that has been studied. Objective: Our objective was to investigate whether single nucleotide polymorphisms in ADAM33 gene are associated with COPD in long-term tobacco smokers in the ethnic Kashmiri population of northern India. Materials and Methods: This was a randomized case-control study, which included 78 stable COPD (GOLD stage11-IV) patients, who were compared with 77 age- and sex-matched long-term tobacco smokers (>20 pack years) without any evidence of COPD. Polymorphic analysis for three single nucleotide polymorphisms (SNPs), (T1, T2, and Q1) of the ADAM33 gene was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing. The data were analyzed by descriptive statistics and comparative evaluation was done by parametric/ non-parametric tests. Results: The analysis of the T1, T2, and Q1 SNPs, revealed that the frequencies of the T2GG, T1GG, and the Q1AG genotypes were significantly higher in patients with COPD in comparison with the controls (P < 0.001). Similarly, the T1G and T2G allele frequency was higher in the patients than in the controls (p=0.177 and 0.43, respectively). Conclusion: Three SNPs of the ADAM33 gene were significantly associated with COPD in the Kashmiri population of India. This study establishes the possible role of ADAM33 SNPS in the causation of COPD. Further studies across different geographical areas in the country will unravel the contribution of this gene in the causation of COPD in India. [ABSTRACT FROM AUTHOR]

Background: Skin prick test (SPT) is the most effective diagnostic test to detect IgE mediated type I allergic reactions like allergic rhinitis, atopic asthma, acute urticaria, food allergy etc. SPTs are done to know allergic sensitivity and applied for devising immunotherapy as the therapeutic modality. Materials and Methods: This prospective study was conducted in the department of Immunology and Molecular medicine at SKIMS. A total of 400 patients suffering from allergic rhinitis, asthma and urticaria were recruited in this study. SPT was performed with panel of allergens including house dust mite, pollens, fungi, dusts, cockroach, sheep wool and dog epithelia. Allergen immunotherapy was given to allergic rhinitis and asthmatic patients as therapeutic modality. Results: In our study, age of patients ranged from 6 to 65 years. Majority of patients were in the age group of 20-30 years (72%) with Male to female ratio of 1:1.5. Of the 400 patients, 248 (62%) had urticaria, 108 (27%) patients had allergic rhinitis and 44 (11%) patients had asthma. SPT reaction was positive in 38 (86.4%) with allergic asthma, 74 (68.5%) patients with allergic rhinitis and 4 (1.6%) patient with urticaria, respectively. Allergen immunotherapy was effective in 58% patients with allergic rhinitis and 42% allergic asthma. Conclusion: Identifiable aeroallergen could be detected in 86.4% allergic asthma and 68.5% allergic rhinitis patients by SPT alone. Pollens were the most prevalent causative allergen. There was significant relief in the severity of symptoms, medication intake with the help of allergen immunotherapy. [ABSTRACT FROM AUTHOR]

Background/Aim: Colorectal cancer (CRC) is one of the leading malignancies worldwide and has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. The aim of this study was to identify p53 and K-ras gene mutations in CRC patients in a Kashmiri population, and to assess whether these mutations are linked with clinicopathological parameters. Materials and Methods: Paired tumor and normal tissue samples from a consecutive series of 53 patients undergoing resective surgery for CRC were prospectively studied for p53 and K-ras gene mutations by PCR/single strand conformation polymorphism (SSCP). Results: Less than half (45%, 19/42) of the patients presented mutations in the p53 gene. Twenty eight mutations were found in the p53 gene, which comprised of 23 substitutions (17 transitions + 6 transversions), and five insertions. The 23 substitutions constituted 18 missense mutations, two nonsense mutations, and three silent mutations. Of the 28 mutations (7.14%) observed in this study, 2 were not previously reported for CRC samples and were identified as novel p53 mutations. A few patients (22.64%, 12/53) presented with mutations in K-ras, constituting 13 missense mutations, out of which 11 were G→A transitions, one was a G→C transversion, and one a G→T transversion. More than half (61.5%) of the mutations occurred in codon 12 whereas a few (38.5%) occurred in codon 13. One tumor contained missense mutations in both codons. Comparison of the mutation profiles of our patients with those of other ethnic populations and regions reflected both differences and similarities, indicating co-exposure to a unique set of risk factors. Conclusion: Mutations of the p53 and K-ras genes are some of the most common genetic changes in the development of human CRC. The high frequency of p53 gene mutations implicates p53 as a predominant factor for CRC in the high-risk ethnic Kashmiri population. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of abnormal glucose tolerance (AGT) among Indian women with polycystic ovary syndrome (PCOS) and analyze the role of oral glucose tolerance (OGTT) test on its estimation.Design: Cross-sectional clinical study.Setting: Tertiary care center.Patient(s): A total of 2,014 women with PCOS diagnosed on the basis of the Rotterdam 2003 criteria were enrolled, and the data of 1,746 subjects were analyzed.Intervention(s): In addition to recording clinical, biochemical, and hormone parameters, a 75 g OGTT was administered.Main Outcome Measure(s): Prevalence of AGT and impact of age, body mass index (BMI), family history, and OGTT on its prevalence.Result(s): The mean age of subjects was 23.8 ± 5.3 years, with a mean BMI of 24.9 ± 4.4 kg/m(2). The overall prevalence of AGT was 36.3% (6.3% diabetes and 30% impaired fasting plasma glucose/impaired glucose tolerance) using American Diabetes Association criteria. The glucose intolerance showed a rising trend with advancing age (30.3%, 35.4%, 51%, and 58.8% in the second, third, fourth, and fifth decades, respectively) and increasing BMI. Family history of diabetes mellitus was present in 54.6% (953/1,746) subjects, and it did not correlate with any of the studied parameters except waist circumference and BMI. Sensitivity was better with 2-hour post-OGTT glucose values as compared with fasting plasma glucose, since using fasting plasma glucose alone would have missed the diagnosis in 107 (6.1%) subjects.Conclusion(s): We conclude that AGT is high among young Indian women with PCOS and that it is not predicted by family history of type 2 DM. OGTT significantly improves the detection rate of AGT among Indian women with PCOS. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome (PCOS) is a multispectral disorder requiring lifelong management. Its pathophysiology is still being explored which makes its treatment options restrained. Present study explores impact of oral contraceptive mode of treatment on metabolic, hormonal, inflammation and coagulation profile of PCOS women. 50 subjects diagnosed with Rotterdam criteria receiving no drug treatment served as controls whereas 50 subjects receiving only OCPs (Ethinyl estradiol 0.03 mg, Levonorgestrel 0.15 mg) as a mode of treatment at least for six-months served as cases. Ferriman-Gallwey score and hormonal profile improved on OCP treatment. However, parameters like weight, Body mass index, waist-hip ratio, Oral glucose tolerance test, lipid profile, insulin, HOMA-IR, adiponectin, interleukin1β, visfatin, resistin, tissue factor, PT and APTT showed considerable derangements in OCP group. All above parameters are associated with the risk of diabetes mellitus, dyslipidemia, coronary vascular disease, cancers, hypercoagulable state, venous thromboembolism and thrombotic events. Long-term use of OCPs needs to be considered carefully for PCOS patients who are already burdened with associated risk factors. This study was conducted in a region where women do not have much access to high-end screening and diagnostic facilities that further exacerbates their clinical outcomes. Large scale, long-term studies need to be designed to further evaluate safety use of OCPs in PCOS women.

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8-12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p  < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.

Apolipoprotein E is a fundamental component of various lipoproteins and plays substantial role in cholesterol/lipid transport among cells of various tissues. The ApoE gene is polymorphic with three alleles ε2, ε3, and ε4, coding for isoforms E2, E3, and E4 having different binding inclination for corresponding receptors. This work aimed to investigate the association between ApoE gene polymorphism and coronary artery disease (CAD) in Kashmiri population. APOE genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. Our study indicated ApoE ε3/ε3 to be the most common genotype in both CAD and control group. The frequency of ε2, ε3, and ε4 alleles of ApoE gene in cases was observed to be 0.06, 0.72, and 0.20, while in control subjects it was 0.075, 0.82, and 0.11, respectively. A significant difference was found between cases and controls with respect to TC, LDL, and HDL levels. Our data showed that frequency of ε4/ε4, ε4/ε3 genotype and ε4 allele was significantly higher in cases than in controls (p = 0.02, p = 0.004, p < 0.001 respectively). Moreover, the CAD patients carrying ε4 allele had significantly higher TC and LDL levels (p value <0.01). Thus our data showed a significant association of ApoE ε4 allele with the risk of CAD. The data revealed that ApoE ε4 allele is associated with increased risk of CAD and increased levels LDL and TC in Kashmiri population.

RAD51 - a DNA double-strand breaks repair gene plays an important role in homologous recombination, a process frequently involved in cancer transformation. The aim of this study was to compare the distribution of the genotype of the RAD51 G135C polymorphism between colorectal cancer (CRC) patients and controls. We also tested the association between the G135C polymorphism of the RAD51 gene and the risk of CRC, and various clinicopathological parameters. Polymorphism was evaluated by restriction fragment length polymorphism PCR in 100 CRC patients and 120 age-matched and sex-matched controls. There was a significant association between RAD51 genotypes and CRC cases (P<0.05). Also, the GC genotype was associated with an increased risk of CRC (odds ratio >3.84). Our results suggest that the G135C polymorphism of the RAD51 gene is associated with an increased risk of CRC in our population.

Objectives: Vitamin D deficiency is common at all ages, and low levels of vitamin D have been associated with high incidence of type 1 diabetes. Similar results are not consistent for type 2 diabetes. The aim of the present study was to estimate vitamin D status in newly detected youth-onset diabetes in north India., Subjects and Methods: This was a prospective case control study at a tertiary care hospital in north India. Seventy two newly detected youth-onset diabetes subjects (age < 25 years), and 41 age- and gender-matched healthy controls were studied. In addition to basic information and management regarding their diabetes, metabolic parameters and serum 25(OH)D were measured in both the groups., Results: Vitamin D deficiency was seen in 91.1% of the subjects with diabetes, and 58.5% of the healthy controls. Mean ±SD 25(OH)D was significantly low, 7.88 ± 1.20 ng/mL in subjects with diabetes against 16.64 ± 7.83 ng/mL in controls. Sixty percent of cases had severe Vitamin D deficiency compared with 8.3% in controls. Levels of vitamin D did not correlate with clinical parameters, such as gender, body mass index; or with biochemical parameters, such as serum calcium, phosphorus, alkaline phosphatase, fasting plasma glucose, and HbA1C., Conclusion: Vitamin D deficiency is common in people with youth-onset diabetes.

Hypermethylation of the promoter region of the p16INK4a (p16) gene plays a significant role in the development and progression of colorectal cancer (CRC). The aim of the present study was to establish the role of the methylation status of the p16 gene in 114 CRC cases and to correlate it with the various clinicopathological parameters. Analysis of p16 promoter methylation was performed by methylation-specific PCR. Forty-eight (42.1%) of the CRC cases were found to be methylated for the p16 gene in our population. The methylation status was found to be associated with the gender, lymph node status, tumour stage, smoking status and tumour grade of the CRC patients. p16 plays a pivotal role in tumour development and progression to advanced stages.

The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (APC) and β-catenin plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the APC and β-catenin genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR) of the APC gene and exon 3 of the β-catenin gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the APC gene was also carried out using methylation-specific PCR (MS-PCR). The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86). Promoter hypermethylation of APC was observed in 54.65 per cent (47 of 86) of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the APC gene (p ≤ 0.05). Although the number of mutations in the APC and β-catenin genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, APC, of the Wnt pathway in the development of CRC in the Kashmiri population.

Background: The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype., Methods: We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of SMAD4 and exon 1 of KRAS by PCR-SSCP and/or PCR-Direct sequencing., Results: The overall mutation rate of mutation cluster region (MCR) region of SMAD4 gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the SMAD4 gene mutants were found to have mutations in KRAS gene as well. The association between the KRAS mutant genotype with SMAD4 mutants was found to be significant (P = or < 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the SMAD4 gene (P = or < 0.05)., Conclusion: Our study suggests that SMAD4 gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the KRAS mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.

Purpose: To assess the frequency of specific point mutations in the K-ras gene in a group of Kashmiri patients with bladder cancer., Materials and Methods: We analyzed the incidence of K-ras exon 1 gene mutations in tumors and surgical margins in 60 patients with transitional cell carcinoma of varied clinical stages and histological grades using the polymerase chain reaction-single strand conformation polymorphism and DNA sequencing., Results: A significant correlation was found between the K-ras, the lymph node status, and tumor recurrence (P < 0.05). Also, smokers and patients with higher tumor grade showed a significantly higher relative risk of developing K-ras mutations than the normal ones., Conclusion: K-ras exon 1 gene mutations were found with low frequency in the bladder cancer tumors from Kashmir valley, which suggests that K-ras gene might be involved in a sub-set of bladder tumors, but it needs further investigation on a larger cohort sample to authenticate the current findings.

The C609T single nucleotide polymorphism of the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene has been identified as an important risk parameter for the susceptibility to colorectal cancer. We here carried out a case-control study and examined the genotype distribution of NQO1 C609T (Pro189Ser) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, to investigate the possible role of this SNP as a risk factor in colorectal cancer development in Kasmir, India. We investigated the genotype distribution in 86 CRC cases in comparison with 160 healthy subjects and also focused on clinicopathological variables in the CRC cases. The observed genotype frequencies in cases and controls were significantly different [OR=1.64; 95%CI=0.94-2.86]. We also found a significant association between the Ser/Ser variant form with age group, smoking status, tumor location, nodal status/ higher tumor grade and with exposure to pesticides. Therefore, we suggest that the NQO1 C609T SNP is involved either in susceptibility or development of CRC in the ethnic Kashmiri population.

Background and Aims: The objective of this study was to assess the frequency of specific-point mutations in N-ras of the RAS gene family in a group of Kashmiri patients with bladder cancer and to observe any association with clinicopathological parameters., Methods: Paired tumor and normal tissue specimens of 55 consecutive patients with urothelial cell carcinoma were screened and DNA was extracted for detection of N-ras activating mutations in exons 1 and 2. In addition, blood was also collected from all the cases to rule out any germ line mutation., Results: Specific point mutations of activated N-ras were detected in 9% (5 of 55) of the bladder cancer patients, all being missense. The base substitutions identified included three transversions (two G toT and one A to T) and two transitions ( A-G). Sixty % of the mutations were detected in codon 61 and 40% in codon 12. No significant correlations were found between the mutations and clinical features., Conclusion: Although N-ras gene mutation might be one of the mechanisms underlying oncogenesis of urothelial cancer, it seems to be a relatively rare event in Kasmiris, pointing to involvement of different etiological factors in the induction of bladder tumor in this population.