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Background:. The MNS16A variable number tandem repeat (VNTR) polymorphism of the human telomerase reverse transcriptase (hTERT) gene acts as a regulator of hTERT promoter activity and has been shown to have a role in the predisposition toward various cancers. The current study aimed to investigate the association between MNS16A VNTR alleles and genetic predisposition to bladder cancer in the Kashmir region of northern India. Materials and methods:. A total of 130 patients with bladder cancer and 170 age- and gender-matched healthy controls were included in this study. Primer-specific polymerase chain reaction was used to genotype the different variants of VNTR alleles of the MNS16A VNTR polymorphism. Results:. Short allele VNTR-243 (SS) genotype frequency significantly differed between cases (9.23%) and controls (3.52%) (OR = 3.08 [95% CI = 1.10–8.61], p = 0.042). The VNTR-243 short allele (S) was found significantly more frequent in bladder cancer cases (28.46%) than controls (20.88%) (OR = 1.50 [95% CI = 1.03–2.19], p = 0.034). Likewise, the long allele (LL) hTERT MNS16A genotype was distributed more frequently in low stage disease versus high stage disease (60.29% vs. 39.70%) (OR = 0.79 [95% CI = 0.39–1.60], p = 0.595). Conclusion:. The MNS16A VNTR short allele (S) was associated with a higher risk for bladder cancer in our population as compared to long alleles.

Aim There is an urgent need to set up a useful biomarker for ovarian cancer. Galectin-1 is a promising carbohydrate-binding protein which plays a remarkable role in various malignancies yet its clinical significance is questionable. In this study, we have tested the clinical implications of serum Galectin-1 levels in patients with ovarian tumours. Main methods Serum Galectin-1 levels were quantified in 84 newly diagnosed ovarian tumour patients and 20 healthy controls by Enzyme Linked Immuno Sorbent Assay during the course of the disease. Therefore the samples were taken at diagnosis, after surgery and after chemotherapy. Key findings The Galectin-1 levels were found to be associated with various variables of Ovarian Cancer patients. The levels were found to be prominently high in postmenopausal patients. Galectin-1 levels were raised in epithelial ovarian tumours with significantly high levels in serous subtype. A decrease in Galectin-1 levels post-surgical intervention and after receiving chemotherapy was found. Galectin-1 levels evidently distinguished between normal, benign, malignant and metastatic cases as compared to CA125 levels. Galectin-1 demonstrated to be a better biomarker than CA125 according to the Receiver Operating Characteristic (ROC) curve analysis. Significance The study emphasizes that serum Galectin-1 may serve as a better surrogate biomarker in Ovarian Cancer for early detection, discriminating between malignant and benign abdominal masses and monitoring the progression of the disease and response to treatment.

Background Allergen immunotherapy (AIT) is a promising treatment for allergic disease that induces immunological tolerance through the administration of specific allergens. The study of AIT is in its early stage and its clinical effects are not well elucidated. The present study was aimed at determining the effect of AIT on pulmonary function and serum variables of mild allergic asthma patients. Methods A total of 80 patients with mild allergic asthma were recruited for the study. Allergen Specific Immunotherapy was administered in the form of Sublingual Immunotherapy and consisted of a build up phase followed by a maintenance phase (six months each respectively). Total serum IgE and vitamin D levels were quantified by ELISA. The percent eosinophill count was determined by cell analyzers. Pulmonary function test was performed at the baseline and after the end of study period. Subjective symptom score was recorded in the form of asthma control questionnaire score. Results There was a significant increase in the pre FEV1% and pre FEV1/FVC post AIT administration. A significant decrease in the total serum IgE was found post AIT. A decrease in Asthma control Questionnaire (ACQ) scores indicated an improvement in clinical symptoms. Besides there was a significant effect on ICS discontinuation after AIT. Conclusion The study supports SLIT as an effective treatment for Immunomodulation in mild allergic asthmatics besides it gives us significant information regarding the safety and efficacy of SLIT in such patients.

INTRODUCTION Glutathione S-transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to tyrosine kinase inhibitors in chronic myeloid leukemia (CML). We aimed to analyze relation of different GST gene sequence variants with susceptibility and response to Imatinib in CML. MATERIAL AND METHODS A total of 150 CML cases and equal number of age and gender matched healthy controls were genotyped for five GST polymorphisms by multiplex-PCR and PCR-RFLP techniques. BCR-ABL1 transcripts were quantified by quantitative Real Time PCR (qRT-PCR). RESULTS GSTT1, GSTO1, and GSTO2 SNPs revealed no association, while as GSTM1null genotype was observed to protect against the development of CML (OR = 0.53, P = .01). GSTP1 variant genotypes AG (OR = 2.1, P = .003) and GG (OR = 5.6, P

Fernandoa adenophylla (Wall. ex G. Don) Steenis is traditionally used to cure various diseases and can be included as an ingredient in massage oils, which are supposed to comfort muscular tension and pain. This study was designed to assess the antinociceptive, muscle relaxant, and molecular docking properties of a novel compound, namely, (5aR,5a1R,6R,7aS,14bR,15R)15-hydroxy-7a-methyl-6-(2-methylprop-1-en-1-yl)-7,7a,14b,15-tetrahydro-5H-t-5a,15methanobenzo[g]benzo[5,6]azuleno[1,8-bc]chromene-5,9,14,16(5a1H,6H)- tetraone (peshawaraquinone), isolated from the methanolic extract of F. adenophylla in an animal model. The chemical structure of the isolated compound was elucidated using advanced spectroscopic techniques and further confirmed by XRD analysis. Compound 1 was tested against hot plate-induced noxious stimuli at various doses (2.5, 5, 10, and 15 mg/kg i.p.). The muscle relaxation potency of compound 1 was evaluated in the inclined and traction test, while the open-field test was used for the determination of sedative potential. The isolated compound was also subjected to acute toxicity analysis. The compound was then subjected to molecular docking analysis to determine the exact mechanism of action. Compound 1 demonstrated significant (p < 0.05) analgesic effect in a dose-dependent manner. A noticeable muscle relaxant effect was observed with the passage of time in both experimental models. The compound 1 showed a significant (p < 0.05) sedative effect, and in an acute toxicity study, the compound 1 was devoid of any noxious effects. The docking studies showed preferential affinity for μ-opioid and GABAA receptors. Hence, the prospective antinociceptive and muscle relaxant and sedative properties are probably mediated through these two target interactions.

Inherited polymorphic sequence variations in drug transport genes like ABCB1 impact a portion of patients with hematologic malignancies that show intrinsic or acquire resistance to treatment. Keeping in view inter-individual sensitivities for such drugs, we through this case–control study tested whether ABCB1 C3435T and G2677T polymorphisms have any influence on the risk and treatment response in patients with chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Genotyping for ABCB1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism in 100 CML and 80 B-ALL patients along with 100 age and gender matched healthy controls. ABCB1 C3435T and G2677T polymorphism showed no association with CML. Genotype distribution revealed significant higher frequency of TT genotype for both SNPs in B-ALL cases and associated with increased B-ALL risk (OR 2.5, p = 0.04 for 3435TT; OR 2.4, p = 0.04 for 2677TT). There was no significant difference in genotype frequency of 3435C > T and 2677G > T among resistant and responsive groups for the two leukemia types. Kaplan–Meier survival plots revealed significantly lower event free survival in CML and B-ALL patients that were carriers of 3435TT genotype (p

IntroductionGlutathione S-transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to chemotherapy in acute lymphoblastic leukemia (ALL). This case–control study investigated the association of GST gene polymorphisms with the etiology and therapeutic outcome of B-ALL among Kashmiri population.MethodsA total of 300 individuals including 150 newly diagnosed B-ALL patients and an equal number of age and gender matched controls were genotyped for five GST gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism technique (PCR-RFLP) and multiplex PCR techniques.ResultsHigher frequency of GSTT1null, GSTO2-AG, and GSTO2-GG genotypes was observed in ALL cases compared to controls that associated significantly with ALL risk (GSTT1null: OR = 2.93, p = 0.0001; GSTO2-AG: OR = 2.58, p = 0.01; GSTO2-GG: OR = 3.13, p = 0.01). GSTM1, GSTP1, and GSTO1 SNPs showed no significant association (p > 0.05). Combined genotype analysis revealed significant association of GSTT1null/GSTM1null (OR = 4.11, p = 0.011) and GSTT1null/GSTP1-AG (OR = 4.93, p = 0.0003) with B-ALL susceptibility. Haplotype analysis of rs4925 and rs156697 revealed that carriers of CG haplotype had increased risk of B-ALL (p = 0.04). Kaplan–Meier plots revealed significantly inferior 3-year disease-free survival for GSTO2-GG carriers (p = 0.002). Multivariate analysis confirmed GSTO2-GG as an independent poor prognostic factor for DFS (HR = 4.5, p = 0.034). Among combined genotypes, only GSTT1null/GSTP1-AG associated significantly with poorer DFS rates (p = 0.032).ConclusionThis study demonstrated that GSTT1null individually or in combination with GSTM1null and GSTP1-AG genotypes associated with increased B-ALL risk. Also, rs156697 variant genotypes (AG and GG) associated with B-ALL, whereas the GG genotype of rs156697 influenced the treatment outcome.

Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders that induces immunological tolerance through administration of specific allergens. Studies on AIT for subcutaneous route are in abundance; however, the efficacy of AIT in tablet form through sublingual route has not been well elucidated. The present prospective, parallel-group, controlled study sought to compare the efficacy of sublingual immunotherapy (SLIT) tablets with pharmacotherapy (PT) in 332 house dust mite (HDM)-specific allergic asthma and/or rhinitis patients over a period of 3 years. Patients were followed up for a 6-month run-in period and then randomly stratified as those who would receive SLIT, SLIT in addition to PT (SLIT+PT), and PT alone. AIT was administered in the form of sublingual tablets. Symptom and medication scores were measured every 3 months. In vitro evaluation of serum total and HDM specific immunoglobulin E (HDM sIgE) levels was carried out every 3 months, whereas in vivo skin prick test was performed annually for 3 years. Our study demonstrated sustained clinical improvement, reduction in inhaled corticosteroid (ICS) dose and duration as well as prevention from development of neosensitization to other aero allergens in HDM-allergic asthmatics and/or rhinitis patients treated with 3 years SLIT. Despite a remarkable clinical improvement with AIT, we observed that SLIT did not significantly change the skin reactivity to HDM at 3 years and there was no significant change in the ratio of serum total and HDM sIgE. Given the immune and disease modifying effects of AIT in allergic diseases, the present study supports the notion of its sublingual mode being an effective long-term immunomodulator in HDM-sensitized nasobronchial allergies.

Deleted in colorectal carcinoma (DCC) A > G (rs714) is the most widely studied SNP of tumor suppressor DCC gene found to be associated with increased risk of various cancers. Therefore, the aim of ...

Glutathione-S-transferase T1 (GSTT1) and glutathione-S-transferase M1 (GSTM1) genes are associated with increase susceptibility to developing different types of cancers. The aim of present study wa...

Background Mismatch repair proteins are ubiquitous keys in diverse cellular functions and protects the genome by correcting mismatch as post replication error correction machinery. Mismatch repair deficiency was associated with tumor development and progression therefore, current study was aimed to investigate MLH1 and MSH2 expression in breast cancer and correlate patients' clinicopathological factors with status of mismatch repair genes. Material and methods Breast cancer tissues with adjacent normal tissue along with clinical details were collected during surgery from 80 cases. Immunohistochemistry was performed with primary and secondary antibodies for expressional analysis. Results were analyzed using SPSS version 24. Results Immunohistochemical analysis revealed that both MLH1 and MSH2 were crucial in maintaining DNA repair system and loss of these 2 mismatch repair proteins may lead to adverse outcomes in breast cancer. Statistically significant association was found between loss of MLH1 (P = 0.0004; odds ratio 13.8; 95% confidence interval 4.6-41.1), MSH2 (P = 0.0002; odds ratio 14.0; 95% confidence interval 4.7-42.2) and breast cancer. Statistical analysis demonstrated that MLH1 and MSH2 deficiency may lead breast cancer progression to advanced stage, correlated with tumor focality (MLH1 P = 0.001; MSH2 P = 0.002) and chemotherapy (MLH1 P = 0.01; MSH2 P = 0.04). Presence of CK7, GATA 3, and E cadherin tends to increase in mismatch repair deficient breast cancer. Whereas, no association of mismatch repair deficiency was observed with age, tumor grade, positive lymph nodes, menopause, and ER and/or PR status. Conclusion Loss of mismatch repair proteins in breast cancer highlights its potential role in DNA repair mechanisms and helps tumor cells to become resistant against chemotherapeutic drugs. Therefore, mismatch repair deficiency may contribute to breast cancer progression.

Studies on polymorphisms in ABCB1 (ATP Binding Cassette subfamily B member 1) gene have shown importance in CML treatment. 42 CML patients comprising 18 males (42.86%) and 24 females (57.14%) aged from 7 to 75 years, of which 19 (45.24%) belonged to age group of ≤45 years and the rest 23 (54.76%) were >45 years of age. A case-control analysis of 3435C>T and 2677G>T ABCB1 single nucleotide polymorphisms (SNPs) with respect to imatinib treatment outcome and evaluation of correlation, if any, with molecular (both qualitative & quantitative) and cytogenetic responses of the patients at 01 year was done by Multiplex RT-PCR, PCR-RFLP, quantitative real time PCR and cytogenetics. No association of any statistical significance was noted between either of the two SNPs and the imatinib treatment outcome.

Background: Allergic diseases are hypersensitivity disorders induced by an allergen specific immunoglobulin E (IgE) mediated response; Skin PrickTest (SPT) remains the gold standard for the in vivo assessment of IgEs. Many drugs are known to have anti histaminic effects and as such need to be stopped prior to the testing. However, the role of alternative system of medicine and other herbal remedies remains controversial in this regard. Objectives: To study the effect of alternative system of medicine and other herbal remedies on the results of SPT. Methods: The patients having a strong history and clinical symptoms of allergic diseases like allergic rhinitis, bronchial asthma and chronic urticaria were subjected to skin prick testing. Results: There were six patients whose SPT results were negative although history and clinical symptoms suggested otherwise. On probing the drug intake of the patients prior to the testing, it was observed that the patients had taken certain herbal medications which interfered with the allergy testing and gave false negatives. Conclusion: It is for the first time that a study has reported the significant effect of alternative medicine and other herbal supplements in suppression of skin prick test results. Therefore it is extremely important to ask properly the history of intake of alternative medicine and other dietary herbal ingredients and then insist on its abstinence for 10 days before SPT. A protocol wherein the allergist recommends to stop the use of any regional herbs prior to allergy testing will be the right step in improving the results of allergy testing and preventing false positives. Keywords: Allergic disorders, Skin prick testing (SPT), Alternative medicine, Antihistaminic response

Carotenoids in food substances are believed to have health benefits by lowering the risk of diseases. Lutein, a carotenoid compound, is one of the essential nutrients available in green leafy vegetables (kale, broccoli, spinach, lettuce, and peas), along with other foods, such as eggs. As nutrition plays a pivotal role in maintaining human health, lutein, as a nutritional substance, confers promising benefits against numerous health issues, including neurological disorders, eye diseases, skin irritation, etc. This review describes the in-depth health beneficial effects of lutein. As yet, a minimal amount of literature has been undertaken to consider all its promising bioactivities. The step-by-step biosynthesis of lutein has also been taken into account in this review. Besides, this review demonstrates the drug interactions of lutein with β-carotene, as well as safety concerns and dosage. The potential benefits of lutein have been assessed against neurological disorders, eye diseases, cardiac complications, microbial infections, skin irritation, bone decay, etc. Additionally, recent studies ascertained the significance of lutein nanoformulations in the amelioration of eye disorders, which are also considered in this review. Moreover, a possible approach for the use of lutein in bioactive functional foods will be discussed.

SARS-CoV-2 belongs to the genera Beta coronavirus with a spherical or pleomorphic virus enveloped particles. The SARS-CoV-2 has sequence homology with severe acute respiratory syndrome-related coronaviruses (SARSr-CoV) and acts on ACE2 (Angiotensin Converting Enzyme 2) receptor by using its spike proteins. The latter are primed by the enzyme, TMPRSS2 protease to complete this process for its entry into the cells [1-3]. The SARSr-CoV has a single-stranded positive-sense ribonucleic acid (RNA) as a genomic material associated with a nucleoprotein within a capsid comprised of matrix proteins. The envelope bears a club-shaped glycoprotein projection containing haemagglutinin-esterase proteins (HE) also. The size of Coronaviruses genome is around (26.4-31.7Kb), which is one of the largest genomes in RNA known viruses and bears the GC content of approximately 32 to 43%. The viral genome contains distinctive features including a unique N terminal fragment within the spike proteins. The genome contains a variable number of ORF (6–11) between the various conserved genes (ORF1ab, spike, envelope, membrane and nucleocapsid [4]. Two third of the SARS-CoV-2 viral RNA is located in the ORF (ORF1a/b) and synthesise polypeptides pp1a and pp1a, and 16 non-structural proteins (NSP) are encoded by these ORFs, and the remaining accessory proteins are translated by other ORFs. The genome that encodes essential structural proteins which are important in the pathogenicity of SARS-CoV-2 like spike (S) glycoprotein, small envelope (E) protein, matrix (M) protein, and nucleocapsid (N) protein are translated by the rest of the viral genome [5].

BACKGROUND: The association between thyroid dysfunction and postoperative mortality is contentious. Thyroid function is frequently depressed during and after cardiopulmonary bypass surgical procedures, and this may adversely affect myocardial performance and postop outcome.OBJECTIVES: To study i) the changes and clinical significance of serum thyroid hormones during cardiopulmonary bypass (CPB), and ii) the association between biochemically assessed peri-op thyroid function and 30-day mortality after CBPSTUDY DESIGN: Prospective Cohort StudySUBJECTS: 279 patients undergoing various cardiac surgeries under cardiopulmonary bypass.METHODS: All consenting patients undergoing open heart surgery in last five years at a tertiary care centre in North-India were studied. The thyroid hormone levels (Total T3, T4 and TSH) were measured before admission, and postoperatively on Day 1 & 7, and 3 months following surgery. The patients’ gender, age, weight, body mass index, heart disease details, previous cardiac surgeries, and cardiac surgery-related data such as pump time, aortic clamping time, hypothermia duration, postoperative hemodynamic status and postoperative use of inotropic drugs were recorded and analysed. Patients were classified as having biochemically overt or subclinical hyperthyroidism or hypothyroidism, normal thyroid function, or non-classifiable state based on preoperative thyroid-stimulating hormone and total T4 values. Outcome data were collected from hospital records. Biochemical thyroid dysfunction was not systematically treated. Outcomes measured were length of ICU stay, postoperative complications and 30-day mortality.RESULTS: There was significant changes in thyroid function in patients undergoing cardiopulmonary bypass surgery (Fig 1). All patients showed a decrease in T3, T4 and TSH after surgery. Post-op complications were observed in 137 patients (49%) most common being atrial fibrillation (34%) followed by acute kidney injury (23%), infections (18%), dyselectrolytemia (7%), bleeding (1.4%) and ARDS (1.4%). Of 263 patients followed, eventually 26 patients expired with a mortality rate of 8.89% (95% CI, 0.4 - 19.4). Perioperatively, there was a significant correlation between 30-day with type of surgery (r, 0.26), aortic clamp time (r, 0.45), CBP time (r, 0.48), number of inotropes used (r, 0.57), hours of mechanical ventilation (r, 0.4), ICU stay (r, 0.13) and post-op complications (r, 0.24), as well as with the reduction in the thyroid hormone levels; 17 (7%), 3 (20%) and 6 (46%) patients of those with pre-op TSH level of 6.5 and >10.5 mIU/L expired (p oTable 1. Characteristics of patients who expired versus those who survived cardiac surgery with cardiopulmonary bypass (CPB) oFig 1. Changes in serum thyroid hormones during CPB surgery oTable 1. Characteristics of patients who expired versus those who survived cardiac surgery with cardiopulmonary bypass (CPB) oFigures in parenthesis indicate ±Standard Deviation, unless indicated otherwise oFig 1. Changes in serum thyroid hormones during CPB surgery

Kaempferol, a natural flavonoid present in several plants, possesses a wide range of therapeutic properties such as antioxidant, anticancer, and anti-inflammatory. It has a significant role in reducing cancer and can act as a therapeutic agent in the treatment of diseases and ailments such as diabetes, obesity, cardiovascular diseases, oxidative stress, asthma, and microbial contamination disorders. Kaempferol acts through different mechanisms: It induces apoptosis (HeLa cervical cancer cells), decreases cell viability (G2/M phase), downregulates phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) and human T-cell leukemia/lymphoma virus-I (HTLV-I) signaling pathways, suppresses protein expression of epithelial-mesenchymal transition (EMT)-related markers including N-cadherin, E-cadherin, Slug, and Snail, and metastasis-related markers such as matrix metallopeptidase 2 (MMP-2). Accordingly, the aim of the present review is to collect information pertaining to the effective role of kaempferol against various degenerative disorders, summarize the antioxidant, anti-inflammatory, anticancer, antidiabetic, and antiaging effects of kaempferol and to review the progress of recent research and available data on kaempferol as a protective and chemotherapeutic agent against several ailments.

The phenomenon of imatinib resistance in Chronic Myeloid Leukemia (CML) can be mediated by “BCR-ABL fusion transcript dependent” and “BCR-ABL fusion transcript independent” pathways. The main means of “BCR-ABL fusion transcript dependent” pathway, responsible for 40–90% of such cases, is the occurrence of Kinase Domain (KD) mutations. The aim of this study was to evaluate the commonly occurring KD mutations like G250, Y253, E255, T315, F317, M351, F359, and H396 for imatinib resistance in CML patients from Kashmir (North India). A total of 42 confirmed cases of CML were subjected to reverse transcriptase polymerase chain reaction (RT-PCR). Kinase Domain PCR-amplicons, derived from the amplification of respective patient's cDNA following reverse transcription of BCR-ABL fusion mRNA, were subjected to nucleotide sequence analysis by ‘Genetic Analyser’ sequencing platform ABI 3500. CML patients included 18 males (42.85%) and 24 females (57.14%) aged from 7 to 75 years, of which 19 cases (45.23%) belonged to age group of ≤45 years and the rest 23 cases (54.76%) were >45 years of age. Sequence analysis was carried out to all the 42 patients at baseline and only on suspected resistant cases at designated follow-ups of 3 months, 6 months and one year. The overall incidence of imatinib resistance in our patients was very low as there were only 8 patients (19.04%), of which 6 cases (14.28%) reported with ‘No cytogenetic response’ (NCR) at 3 months and 1 each having lost earlier attained ‘Complete cytogenetic response’ (CCR) and molecular response at 6 months. These 8 patients were enlisted as suspected imatinib resistant cases and were subjected to imatinib resistance mutation analysis (IRMA) by sequencing at successive designated follow-up periods as applicable. No imatinib resistance mutations were detected in the patients either at baseline or across all the follow-up durations implying other causes for imatinib resistance in CML patients of our region.

Objective: Arrhythmogenic cardiomyopathy (ACM) is not an uncommon cause of cardiac morbidity in Kashmir valley. This study was designed to document various clinical features and to sequence exons 11 and 12 of plakophilin 2 (PKP2) gene in these patients. Methods: ACM patients who attended cardiology outpatient department of our institute from January 2014 to April 2015 were included in the study. Their records were reviewed. Controls were randomly selected, who had no history or family history of cardiac illness and had a normal cardiac examination. A blood sample was also taken from both the groups for sequencing of exon 11 and 12 of PKP2 gene. ACM patients were followed up until July 2016. Results: Eleven ACM patients and seven controls were included in the study. Most common mode of presentation was ventricular tachycardia (VT). Two patients had left ventricular (LV) systolic dysfunction. One patient had a splice site mutation in exon 12 of PKP2 gene and one patient died during follow-up. One of the controls had an intronic variation that has no pathogenic significance vis-à-vis ACM. Conclusion: Our study describes various clinical parameters in ACM patients and a recessive plakophilin 2 mutation after a limited PKP2 gene sequencing. Keywords: Arrhythmogenic right ventricular dysplasia, Plakophilin 2 gene, Splice site mutation, Ventricular tachycardia

Sublingual immunotherapy (SLIT) with house dust mite (HDM) preparation has been shown to reduce disease severity in patientswith atopic dermatitis (AD). A 5-year-old girl with severe Atopic Dermatitis refractive to all possible pharmacotherapy was put onSLIT for dust mite and followed up for a period of one year. SLIT to dust mite proved highly effective in reducing the disease severityscore as well as prevention of exacerbations in this patient.

Apolipoprotein A1 (APOA1) is a potential biomarker because of its variable concentration in different types of cancers. The current study is the first of its kind to evaluate the association between the APOA1 genotypes of −75 G/A and +83 C/T in tandem with the APOA1 protein expression in urine samples to find out the risk and potential relationship for differentially expressed urinary proteins and APOA1 genotypes. The study included 108 cases of bladder tumors and 150 healthy controls that were frequency matched to cases with respect to age, sex, and smoking status. Genotyping was performed using PCR-RFLP and the urinary expression of the APOA1 protein was done using ELISA. Bladder tumor cases were significantly associated with the APOA1 −75 AA genotype (p &lt, 0.05), while the APOA1 +83 C/T heterozygotes showed an association with cases (p &lt, 0.05). The overall distribution of the different haplotypes showed a marked difference between the cases and controls in GT when compared with the wild type GC (p &lt, 0.03). Bladder tumor cases that carried the variant genotype APOA1 −75AA were found more (70.0%) with a higher expression (≥20 ng/mL)of the APOA1 urinary protein and differed significantly against wild type GG (p = 0.03).Again, in low grade bladder tumors, urinary APOA1 protein was exhibited significantly more (52.4% vs. 15.4% high grade) with a higher expression (≥20 ng), while high grade tumor cases (84.6% vs. 47.5% low grade) showed a lower APOA1 expression (&lt, 20 ng/mL) (O.R = 6.08, p = 0.002). A strong association was observed between APOA1 −75G/A and risk for bladder tumor and its relation to urinary protein expression, which substantiates its possible role as a marker for the risk assessment of the disease and as a promising diagnostic marker for different grades of malignant bladder tumors.

Health risks of heavy metals in vegetables irrigated with sewage water were investigated in the present study. The findings indicated a massive accumulation of heavy metals in soil and vegetables collected from Dera Ismail khan, Pakistan. The concentration levels of heavy metal in vegetables grown on soil irrigated with untreated sewage water were significantly higher at (P ≤ 0.001) than in vegetables grown on fresh-water-irrigated soil and proceeded the recommended limits of World health organization. Moreover, the findings also indicated that the adults and children consuming such vegetables ingested a large proportion of the selected toxic metals. Health risk index was greater than one for Pb and Cd in all the selected vegetables and was greater than one for Ni in three vegetables like Spinacia oleracea, Benincasa fistulosa and Lactuca sativa. Health risk assessment would be a useful tool for information regarding any threats of heavy metals contamination in vegetables.

Purpose The p15Ink4b gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India). Materials and Methods p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction, while its subsequent expression analysiswas carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Results Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA. Conclusion Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

Illiteracy is a major hurdle in socio-economic development of Pakistan. Research in the Information and Communication Technology (ICT) can help in tackling this issue by developing solutions tailored for illiterate population. The work presented within this paper proposes a job search website for illiterate population of KPK province of Pakistan. The designed website does not require any human assistance while searching a job. Moreover, the website uses culturally relevant graphical and audio content. The usability of the website is tested according to the ISO-9241-11 specification. Furthermore, we have studied the effect of the participants’ characteristics, i.e., their age, computer and mobile usage experience on the usability of the website. The results show that the participants found the website usable. Specifically, they could search suitable jobs with a minimal number of clicks and in less time as compared to the usual task completion rates reported throughout the literature. None of the participants’ characteristics were found to be affecting the usability of the website. These results suggest a promising potential of ICT solutions for providing services to illiterate population of Pakistan.

The well-established molecular pathogenesis of chronic myelogenous leukemia (CML) and its consequences for laboratory testing and clinical management illustrate a classic paradigm for the importance of molecular diagnostics in targeted drug therapy. The success of the tyrosine kinase inhibitor (TKI), Imatinib, as the currently recommended first-line treatment of early chronic phase CMLhas both fueled the need for timely and reproducible molecular testing of the BCR-ABL fusion transcript in diagnosis and monitoring. As ongoing research continues to refine guidelines for monitoring residual disease in patients undergoing TKI therapy, an understanding of molecular technologies and their interpretation is critical. In this regard, we at Cancer Diagnostic and Research Centre, Immunology and Molecular Medicine established a gold standard RT-PCR and RQ-PCR technique to diagnose and monitor residual disease in CMLpatients. JMS 2016; 19(2):82-84

Chrysin is a promising phytochemical that is categorized under the class of flavonoids based on its chemical structure. Naturally, it is widely present in propolis, honey, passion fruit, and even in mushrooms and other plant sources, whereas its synthetic counterparts are also being employed for pharmacological purposes. It has widely been employed in treatment of various degenerative disorders and provides cytotoxic and anti-inflammatory functions. Its antioxidant and disease preventing abilities are attributed to its structural diversity arising in ring-A and absence of oxygenation in B and C ring. In this review, the scientific studies are being reported emphasizing benefits and its allied health claims on chrysin in numerous metabolic malfunctions.

Background: Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Disorders of salt and water balance are the most commonly recognized medical complications in the immediate post-TBI period and contribute to early morbidity and mortality. Objective: We aimed to evaluate the prevalence of acute (during hospital stay) and chronic posterior pituitary dysfunction in patients of head injury admitted at our tertiary care hospital. Study Design: Prospective, Observational study. Participants: 136 patients, attending tertiary care in North India with TBI with radiological evidence of head injury. Methodology: The severity of brain injury was assessed by the Glasgow Coma Scale (GCS), and Modified Rankin Scale (MRS) score at the time of admission. Lab measurements, apart from routine CBC and biochemical tests, included tests of serum and urinary osmolality, serum sodium, cortisol, and thyroid function test during the hospital stay. All patients were monitored closely during the hospital stay. Surviving patients were evaluated at 3, 6, and 12 months of follow-up. Urinary output and water deprivation tests were done to determine chronic posterior pituitary dysfunction. The results were compared against normative data obtained from 25 matched, healthy controls. Serum & urinary osmolality was measure by the freezing point method. Diabetes insipidus (DI) and Syndrome of inappropriate ADH secretion (SIADH) were diagnosed according to standard criteria. Results: Of 136 patients admitted, 61 (44.85%) had a mild head injury (GCS, ≤8), 47 (35.55%) had a moderate injury (GCS, 9-12), and 27 (19.85%) had a severe injury (GCS, 13-15). DI occurred in 10 patients (7.4%), while SIADH was observed in 4 patients in the immediate TBI period. Risk factors for diabetes insipidus were GCS of ≤ 8 at admission, midline shift, and surgical intervention. DI was an independent risk factor for death. There was a negative correlation between the presence of DI and GCS score (r, -0.367). Most of the patients with DI (8 out of 10) died during the hospital stay. One patient persisted to have partial diabetes insipidus and another one SIADH at three months post-TBI; both patients had recovered at six months of follow-up. No new case of DI or SIADH occurred on the follow up to 12 months. Conclusion: The incidence of acute DI in severe head injury (GCS ≤ 8) could be an indicator of the severity of TBI, and associated with increased mortality as most of our patients died during the hospital stay.

Aims Considering a surge in the incidence of Diabetes mellitus (DM) across all ethnic groups and lack of any representative data from the tribal communities of Jammu and Kashmir, the present study aimed to assess the prevalence of DM and prediabetes in them. Methods Subjects were recruited from five districts of Kashmir valley using multistage cluster sampling by probability proportional to size (PPS) technique. Data collection included recording of socio-demographic, medical facts, assessment of anthropometric parameters and biochemical evaluation HbA1c and random blood glucose measurements as per the American Diabetes Association (ADA) criteria were used for diagnosis of DM. Results A total of 6808 subjects were recruited in this study including 2872 (42%) men and 3936 (58%) women with mean age of 39.60 ± 20.19 years and 35.17 ± 16.70 years, respectively. Around 8.60% subjects were obese, 38.9% were found to be hypertensive, 73% had dyslipidemia and 3.75% had metabolic syndrome. About 1.26% (0.5% males and 0.9% females) had DM and 11.64% had prediabetes based on HbA1c cut offs. Increasing age, body mass index and family history portend significant risk factors while smoking and sedentary lifestyle increased the risk marginally. Conclusions Although the prevalence of DM among tribals of Kashmir valley is lower than general population, the higher prediabetes to DM ratio may indicate a future trend of increasing DM prevalence in this disadvantageous subpopulation.

Background: Parathyroidectomy has been traditionally performed through bilateral neck exploration (BNE). However, with the use of intraoperative parathyroid hormone (IOPTH) assay along with preoperative localization studies, focused parathyroidectomy can be performed with good surgical success rate, multiglandular disease can be predicted, and hence recurrence and surgical failure can be prevented. Furthermore, it predicts eucalcemia in the postoperative period. The aim of this study was to evaluate the usefulness of IOPTH assay in guiding adequate parathyroidectomy in patients of primary hyperparathyroidism. Materials and Methods: Between year 2015 and 2017, 45 patients of primary hyperparathyroidism underwent parathyroidectomy with IOPTH assay employed as an intraoperative tool to guide the surgical procedure. Blood samples were collected: (1) at preincision time, (2) preexcision of gland, (3) 5-min postexcision of gland, and (4) 10-min postexcision of gland. On the basis of the Irvin criterion, an intraoperative PTH drop >50% from the highest either preincision or preexcision level after parathyroid excision was considered a surgical success. Otherwise, BNE was performed and search for other parathyroid glands done. Results: Ten-min postexcision PTH levels dropped >50% in 34 (75.6%) patients. True positive among them were 31 (68.8%), true negative 8 (17.7%), false positive 3 (6.6%), and false negative 3 (6.6%). We performed focused exploration at the outset in 40 (88.9%) patients and bilateral exploration for five patients as guided by preoperative localizing studies. Hence, IOPTH was helpful in guiding further exploration in 8 (17.7%) patients and prevented further exploration in 32 (71.1%) patients and also was able to predict eucalcemia in 97.7% patients at 6 months. Thus, IOPTH was able to obviate or to ask for additional procedure in 88.8% of patients. However, in three (6.6%) patients, IOPTH would guide unnecessary exploration and in equally, that is, three (6.6%) patients may require reoperation for unidentified parathyroids. Conclusion: IOPTH in adjunct with other localizing studies is very helpful for carrying out successful parathyroidectomy in uniglandular disease and predicting postoperative eucalcemia. However, more importantly, its role is valuable in equivocal imaging, in such cases, it prevents unnecessary exploration or helps in adequate parathyroidectomy.

O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy. Sixty three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC). Methylation status of MGMT and loss of protein expression showed a very high concordant association with better survival and progression free survival (PFS) (p

Background Chronic urticaria is termed as idiopathic if there is an absence of any identifiable causes of mast cell and basophil degranulation. Various cytokines have been found to be involved in inflammatory processes associated with chronic idiopathic urticaria, including interleukin (IL) 18 and IL-6. Objective To evaluate any possible correlation of IL-18 and IL-6 cytokines with the clinical disease severity in chronic idiopathic urticaria (CIU). Methods IL-18 and IL-6 levels of CIU patients (n = 62) and healthy controls (n = 27) were assessed by commercially available enzyme linked immunosorbent assay kits following the manufacturer's protocols. Results Serum IL-18 concentration (mean ± standard deviation [SD], 62.95 ± 36.09 pg/mL) in CIU patients and in healthy controls (54.35 ± 18.45 pg/mL) showed no statistical significance (p > 0.05). No statistically significant difference (p > 0.05) was observed between autologous serum skin test (ASST) positive and ASST negative patients with regard to the serum IL-18 levels either. Similarly, serum IL-6 concentration (0.82 ± 4.6 pg/mL) in CIU patients and in healthy controls (0.12 ± 1.7 pg/mL), showed no statistical significance (p > 0.05). Also, comparison between positive and ASST negative patients with regard to the serum IL-6 levels was statistically nonsignificant (p > 0.05). However, statistical significance was found both in IL-18 and IL-6 concentrations in certain grades with regard to the clinical disease severity of urticaria. Conclusion There is no significant association as such found between IL-18 and IL-6 levels with CIU, however, these cytokines may help in predicting the clinical disease severity in CIU. Hence, these cytokines may indicate a potential role as a biomarker to assess the disease severity in CIU.

A strong association between chronic infection, inflammation, and cancer has been suggested.Helicobacter pylori, a microaerophilic gram negative bacterium, infects about half the world's population. It has been defined as a definitive carcinogen in the pathogenesis of gastric cancer. H. pylori evades the host immune responses and persists in the stomach leading to gastritis gastric atrophy and sometimes gastric cancer.Chronic H. pylori infection causes gastric cancer via two mechanisms: the presence of virulence factors and the induction of chronic inflammation which ultimately leads to neoplastic transformation.

Clastogen induced chromosome breakage analysis is widely used for the differential diagnosis of Fanconi's anemia. Mitomycin-C (MMC) induced chromosome fragility test was performed on the cultured lymphocytes of 50 children with clinical suspicion of Fanconi's anemia. According to the results of the MMC test, the patients were divided into two subgroups: FA displaying typical sensitivity to MMC and non FA. The present study revealed 7(14%) of examined patients to have a FA cellular phenotype with increased MMC-induced chromosome fragility. The percentage of MMC-induced aberrant cells was increased more than 36 times in FA patients (Mean=67.14%) when compared to non FA patients (Mean=1.82). The number of MMC-induced breaks/cells was more than 09 times higher in FA patients (Mean=2.42 breaks/cell) when compared to non FA patients (Mean=0.25 breaks/cells). Our results indicate that the clastogen induced sensitivity test is a reliable in vitro method for verification of the FA cellular phenotype. The study being the first of its kind from Kashmir (North India) lays the basis for further studies on patients of this region with a clinical suspicion of FA.

First-Aid guidance is important for both literates and illiterates. Almost all available information about First-Aid on websites is in textual form and is beneficial to literates only. In this research an ICT solution is conceived as an iPhone Operating System (iOS) mobile application to educate illiterate population of Mardan, KPK Pakistan about some basics of First-Aid. Two similar mobile applications were developed with two different interfaces: a sketch-based interface and an image-based interface. Both interfaces were tested on 50 illiterates and 49 students of software engineering to evaluate usability of the application for illiterates. The results showed that the specific hand drawn sketches visualizing different First-Aid activities were better understood by the illiterates as compared to image based interfaces. In addition there was no clear difference of usage between literates and illiterates while they were using sketch based interfaces which shows sketch based interfaces are more usable for both types of users. However, there were significant differences of usage between literates and illiterates while using image based interfaces application showing non-usability of image based interfaces for illiterate population.

Drug allergy is one type of adverse reaction to drugs and encompasses a spectrum of hypersensitivity reactions with heterogeneous mechanisms and clinical presentations. It has been defined by the British Society for Allergy and Clinical Immunology (BSACI) as 'an ADR with an established immunological mechanism' 1,2 . Diagnostic procedures in allergy diagnosis can be classified into the patient's history, in vivo skin testing, in vitro laboratory tests and provocation tests 3 . In situations in which there is a definite medical need for a particular agent, no suitable alternative agent exists, there are primarily two options for the patient with a drug allergy; a procedure to induce temporary drug tolerance can be performed to allow the patient to take the drug safely or a test dose or graded challenge can be administered to determine whether the patient is currently allergic to the particular drug .4 JMS 2016; 19(2):97-98

Background: Conventional cytogenetic studies have been viewed as the standard follow-up method for Chronic Myeloid Leukemia patients on Imatinib. However, this approach is beset with high probability of poor metaphase index. In this study, we evaluated the application of Phytohemagglutinin (PHA)-induced peripheral blood culture based cytogenetic analysis (Karyotyping) in diagnosis and Imatinib treatment monitoring of the Chronic Phase CML patients. Methods: The patient samples were subjected to the PHA-induced peripheral blood culture based cytogenetic technique (Karyotyping) to establish their baseline cytogenetic status followed by their follow up Karyotyping twice at the end of 3 and 6 months of treatment. The simultaneous quantitative PCR (q-PCR) assay for BCR-ABL fusion gene transcript on the samples corresponding to their baseline as well as the follow up cytogenetic status was also carried out to authenticate the cytogenetic findings. Results: Complete Cytogenetic Response (CCR) and Partial Cytogenetic Response (PCR) was initially observed in 09 (30%) and 16 (53.3%) respectively of 30 CML patients with 05 (16.6%) patients showing no such response at the end of 3 months. At 6 months, 25 (83.3%) and 02 (6.6%) showed CCR and PCR respectively with 03 (10%) of patients without any response. The findings completely correlated with the hematological response, the q-PCR assay as well as the overall disease condition observed in the patients. Conclusion: As acquiring bone-marrow sample involves morbid consequences for patients and metaphases yielded thereby are difficult to analyze, PHA-induced peripheral blood Karyotyping was explored as an alternative. It was found to have significant potential in serving as a valid tool in the diagnosis and assessment of follow up response to Imatinib mesylate treatment of patients with chronic phase CML.

Background: Studies have demonstrated that the mutant *2 and*3 allele of the CYP2C19 loss-of-function polymorphism is associated with diminished metabolization of clopidogrel and an attenuated platelet response to clopidogrel treatment. Since no such study has been conducted in this region, we examined CYP2C19 polymorphism in Acute Coronary Syndrome (ACS) patients on clopidogrel treatment, and its effect on the cardiovascular outcomes. Material and Methods: A total of 100 samples of ACS were included in this study and genotyping of CYP2C19 *2 and *3 gene polymorphisms was performed by a Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP). Results: The distribution of CYP2C19*2 allele wild *1/*1, Heterozygous *1/*2 and homozygous mutant *2/*2 genotypes was 56%, 34% and 10% respectively while for CYP2C19*3 wild*1/*1 and heterozygous *1/*3 genotypes was 84% and 16% respectively. The frequency of compound heterozygotes (*2/*3) was found in 9% (9 of 100 patients). CYP2C19 *1/*2 allele was found in 03 of 34 (8.8%) patients who had CV events followed by 2 of 10 (20%) patients with mutant genotype CYP2C19*2 (*2/*2) on follow up. In the CYP2C19*3, 31.2% having heterozygous genotype (*1/*3) had CV events as compared to 11.9% with *1/*1 (31% v/s 11.9% p> 0 .05). In the poor-metabolizer group (*2/*2 or *2/*3), 20.1% of patients had CV events on follow up compared to 15.6% in the extensive metabolizer group (*1/*1), whereas in the intermediate group only 10% of patients had CV events (p>0.05). Conclusion: We conclude that patients carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events than as against those with normal allele. Lack of significant events even in presence of variant alleles justifies us to some extent to continue clopidogrel in our patients

Pleural effusion is one of the commonest presentations of tuberculosis, the clinical manifestations being typically abrupt resembling bacterial pneumonia. Since delayed hypersensitivity is the underlying immune response, bacterial load is very low. Owing to these facts, tuberculous pleurisy as an extra-pulmonary disease poses a diagnostic dilemma. The conventional bacteriological methods rarely detect Mycobacterium tuberculosis in pleural fluid and are of limited use in diagnosis of tuberculous pleurisy. We evaluated the efficacy of polymerase chain reaction (PCR) in the diagnosis of tuberculous pleurisy by targeting the gene segment coding for MPB64 protein specific forMycobacterium tuberculosis. Based on the clinical criteria, 82 patients with lymphocytic exudative pleural effusion were included in the study. Patients were analyzed in two groups; one group consisting of 48 patients of tubercular pleural effusion confimed by various diagnostic procedures and another group of 34 patients comprising of non-tubercular pleural effusion. There were no false positive results by PCR and the specificity worked out to be 100%. Twenty two patients tested positive for Mantoux with a sensitivity of 45%. ZN-staining for AFB was found in samples from 15 patients (20% sensitivity). ADA was positive for 28 patients with a sensitivity of 53%. PCR was positive for 32/48 patients (67% sensitivity). Thus, PCR was found to be more sensitive than any other conventional method in diagnosis of clinically suspected tubercular pleurisy.

Background: Gestational hypertension is a significant threat both to maternal and fetal health. However, it is still a distant dream to predict accurately its occurrence in early pregnancy. Objective was to find out if β HCG levels determined between 13 to 20 weeks of gestation can be used as a predictor for gestational hypertension.Methods: This prospective observational cohort study was conducted from August 2014 to January 2016. Serum β HCG levels were determined at 13 to 20 weeks of gestation of 190 normotensive pregnant women attending the antenatal clinics. They were followed for the development of gestational hypertension till 40 weeks of gestation or delivery.Results: Out of the total 190 women, 25 (13.1%) developed gestation hypertension. Of those who developed gestational hypertension, 22 (88%) were having β HCG levels >2 MOM (p2 MOM were 83.3, 96.9, 80.0 and 97.5 respectively (95% CI).Conclusions: Pregnant women with high Beta HCG levels in early pregnancy have significantly higher risk for development of gestational hypertension.

The aim of our study was to determine the genetic associations between polymorphisms of the IL1β gene (-511C/T and +3953C/T) and IL6 gene (-174G/C) with disease susceptibility and severity in patients with rheumatoid arthritis (RA) in ethnic Kashmiri population.Allele and genotype frequencies of IL1β -511 C/T, IL1β +3953 C/T and IL6 -174 G/C polymorphisms were compared between 150 RA patients and 200 healthy controls by using PCR-RFLP method.We did not find any significant association between IL1b +3953 C/T and IL6 -174 G/C polymorphism and Rheumatoid Arthritis risk (p0.05), but IL1β +3953 CT genotype was associated significantly with increased SJC and ESR and IL6 -174 GG genotype was associated significantly with increased ESR. However IL1b -511C/T polymorphism was significantly associated with rheumatoid arthritis risk and the carriers of IL1β -511 'C' allele (CC and TC genotypes) appeared to have lower risk for RA development.Our findings suggest that the IL1b -511 'C' allele has a protective role from disease development. Furthermore our results suggest a possible role of IL1b +3953 CT and IL6 -174 GG genotypes as disease activity markers of rheumatoid arthritis.

Aim The aim of our study was to determine the genetic associations between polymorphisms of the TNFα gene (-308G/A and -238G/A) with disease susceptibility and severity in patients with rheumatoid arthritis (RA) in an ethnic Kashmiri population. Methods Allele and genotype frequencies of TNFα-308G/A and TNFα-238G/A polymorphisms were compared between 150 RA patients and 200 healthy controls by using polymerase chain reaction – restriction fragment length polymorphism method. Demographic, clinical and serological data were prospectively evaluated. Disease activity score (DAS28) was also assessed. Results We did not find any significant association between TNFα-308G/A and TNFα-238G/A polymorphism and RA risk (P > 0.05), but TNFα-308GG genotype was associated significantly with rheumatoid factor seropositivity (P

Background: Coronary artery disease (CAD) is a major cause of death and disability in developed countries. Chronic stable angina is the initial manifestation of CAD in approximately 50% of the patients. Recent evidence suggests that vitamin D is crucial for cardiovascular health. The prevalence of vitamin D deficiency in our region is 83%. A low level of vitamin D is associated with chronic stable angina. Aim: This study was aimed at supporting or refuting this hypothesis in our population. Materials and Methods: The study was a prospective case-control study. We studied 100 cases of chronic stable angina and compared them with 100 matched controls. Vitamin D deficiency was defined as

Introduction: Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. Materials and Methods: The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). Results: Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. Conclusion: We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine.

Objective: Growth retardation is common in children with extrahepatic portal vein obstruction (EHPVO) and growth hormone (GH) resistance may play a dominant role. The aim of this study was to ascertain growth parameters and growth-related hormones in children with EHPVO, comparing with controls and to study the response of shunt surgery on growth parameters. Materials and Methods: The auxological and growth-related hormone profile (GH; insulin-like growth factor binding protein-3 [IGFBP-3] and IGF-1) of thirty children with EHPVO were compared with controls. The effect of shunt surgery on growth parameters in 12 children was also studied. Results: The mean height standard deviation score (HSDS) of cases (−1.797 ± 1.146) was significantly lower than that of controls (−0.036 ± 0.796); the mean weight SDS of cases (−1.258 ± 0.743) was also lower than that of controls (−0.004 ± 0.533). The mean GH level of cases (5.00 ± 6.46 ng/ml) was significantly higher than that of controls (1.78 ± 2.04 ng/ml). The mean IGF-1 level of cases (100.25 ± 35.93 ng/ml) was significantly lower as compared to controls (233.53 ± 115.06 ng/ml) as was the mean IGFBP-3 level (2976.53 ± 1212.82 ng/ml in cases and 5183.28 ± 1531.28 ng/ml in controls). In 12 patients who underwent shunt surgery, growth parameters significantly improved. Conclusions: Marked decrease in weight and height SDSs associated with GH resistance is seen in children with EHPVO, which improves with shunt surgery.

Nasobronchial allergy is one important type of respiratory disorder. Aero allergens like pollen, dust, fungus, dander and many others play important role in nasobronchial allergies particularly in asthma and rhinitis. The prevalence of nasobronchial allergy among populations all over the world has been increasing rapidly. The role of different inhalant allergens in nasobronchial allergy varies with environmental conditions, type of allergen and degree of exposure. The awareness on the prevalence of allergens and seasonal variations is essential for better diagnosis and immunotherapy. The present study was aimed to assess the prevalence of fungal, pollen and dust allergens by intradermal skin test in nasobronchial allergenic patients in district Kupwara of Jammu and Kashmir State. Key words: Allergens, nasobronchial allergy, intradermal skin test, immunoglobulin-E.

The study was aimed at identifying the presence of specific IgE antibody levels in vitro to antigen. Based on positive skin test with Cynodon dactylon and elevated levels of total IgE (>325 IU/ml), 104 patients were selected. Healthy, asymptomatic individuals (25) with low total IgE (

Objective Specific acquired HRAS mutations have been found to predominate in bladder cancer, and HRAS T81C polymorphism has been determined to contribute the risk of various cancers, including bladder cancer. Materials and methods We screened the exon 1and 2 of HRAS and frequently detected polymorphism at nucleotide 81T to C (exon 1). A case-control study was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to test the genotype distribution of 140 bladder cancer patients in comparison with 160 cancer-free controls from a Kashmiri population. Results In HRAS T 81 C SNP, frequencies of TT , TC , and CC genotypes among controls were 84.4%, 15.6%, and 0.0%, while in cases allele frequencies were 64.3%, 30%, and 5.7%, respectively. A significant differences was observed between the control and cases with odds ratio (OR) = 3.0 and 95% confidence interval (CI) = 1.74–5.20 ( P = 0.000). Interestingly, combined TC and CC genotype abundantly presented in high grade (OR = 5.4 and 95% CI = 2.8–10.2; P P TC+CC ) was found with male subjects (≥50) and ever smokers ( P = 0.001). Conclusion It is evident from our study that HRAS T81C SNP moderately increases bladder cancer risk, and rare allele is a predictive marker of advanced bladder tumors.

Bladder cancer is the second most common genitourinary tumor and constitutes a very heterogeneous disease. Molecular and pathologic studies suggest that low-grade noninvasive and high-grade invasive urothelial cell carcinoma (UCC) arise via distinct pathways. Low-grade noninvasive UCC represent the majority of tumors at presentation. A high proportion of patients with low-grade UCC develop recurrences but usually with no progression to invasive disease. At presentation, a majority of the bladder tumors (70%-80%) are low-grade noninvasive (pTa). Several genetic changes may occur in bladder cancer, but activating mutations in the fibroblast growth factor receptor 3 (FGFR3) genes are the most common and most specific genetic abnormality in bladder cancer. Interestingly, these mutations are associated with bladder tumors of low stage and grade, which makes the FGFR3 mutation the first marker that can be used for diagnosis of noninvasive bladder tumors. Since the first report of FGFR3 involvement in bladder tumors, numerous studies have been conducted to understand its function and thereby confirm the oncogenic role of this receptor particularly in noninvasive groups. Efforts are on to exploit this receptor as a therapeutic target, which holds much promise in the treatment of bladder cancer, particularly low-grade noninvasive tumors. Further studies need to explore the potential use of FGFR3 mutations in bladder cancer diagnosis, prognosis, and in surveillance of patients with bladder cancer. This review focuses on the role of FGFR3 in bladder tumors in the backdrop of various studies published.