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Introduction: Sheehan syndrome (SS) typically involves the loss of anterior pituitary cells and rarely affects the posterior pituitary. The water deprivation test (WDT) is the gold standard for diagnosing central diabetes insipidus (CDI), but it is cumbersome. Serum copeptin measurements are an alternative for CDI diagnosis. In this study, we measured hypoglycaemia-stimulated serum copeptin in SS patients to assess posterior pituitary function alongside anterior pituitary hormone levels. Methods: This study recruited 43 patients with SS on stable hormonal replacement except for growth hormone (GH), 18 patients with CDI, and 19 body mass index (BMI) and parity-matched controls. All patients with SS and four patients with CDI underwent an insulin tolerance test (ITT), and hypoglycaemia-stimulated copeptin levels were measured at 0, 30, 45, and 90 minutes after insulin injection. Results: The mean serum copeptin level among patients with SS (26.01 ± 12.41 pmol/L) was significantly lower than that in healthy controls (31.92 ± 7.85 pmol/L) and higher than that in patients with CDI (1.81 ± 0.14 pmol/L). Using pre-defined cut-offs for CDI, basal serum copeptin 2.69 pmol/L and stimulated copeptin

Hepatitis B virus (HBV) and its associated chronic liver disease pose a significant health hazard. Chronic HBV infection is a major contributor to the development of liver cirrhosis, liver fibrosis, and liver cancer. This study focused on ISG12a and its inhibitory effect in Huh7 cells on HBV gene expression and replication. The mammalian hepatoma cells Huh7 were transfected with the pHBV1.3 vector (pCAGGS) or HA-tagged ISG12a to determine the overexpression, to test this hypothesis further, we did knockdown or silencing by transducing Huh7 cells with lentiviruses containing shRNAs targeting ISG12a or scramble control shRNA (shControl). The expression of ISG12a was evaluated through western blot analysis. The HBsAg and HBeAg secretion in the Huh7 cells’ culture media was examined using an ELISA test. The qRT-PCR confirmed the mRNA and 3.5 mRNA Kb of ISG12a. The HBV total RNA was extracted and evaluated through a Northern blot. The isolated DNA was detected through qPCR. Additionally, a mechanistic study of enhancer II (EnhII/Cp) was examined through luciferase reporter testing. Our research findings indicate that ISG12a, an interferon-stimulated gene (ISG), plays a crucial role in suppressing the replication and gene expression of HBV. According to our study using the Huh7 cell system, overexpression of ISG12a resulted in a notable reduction in HBV protein levels as well as intracellular core-associated DNA and RNA levels. On the other hand, silencing ISG12a in Huh7 cells resulted in increased HBV RNA transcripts, DNA, and secreted proteins, indicating that ISG12a plays a role in suppressing HBV replication. Additionally, the research revealed that ISG12a inhibits the function of the EnhII/Cp promoter, which results in reduced HBV gene expression. The EnhII/Cp promoter is involved in regulating HBV gene expression, and the study showed that ISG12a restricts its activity. ISG12a may have a regulatory role in controlling the expression of HBV genes. These findings highlight the importance of ISG12a in HBV gene expression and provide valuable insights for understanding its antiviral function.

Diabetic foot ulcer (DFU) is one of the most detrimental impacts of diabetes mellitus associated with osteomyelitis and gangrene, accounting for at least two-thirds of non-traumatic amputations with a 5-year survival rate. In this perspective, antimicrobial resistance has been a cause for grave concern for the last 50 years and is among the World Health Organization most pressing “calls to action” for the 21st century. The current study aimed to identify bacterial pathogens present in DFU, their antibiotic resistance profiles, and genetic diversity. A total of 180 samples were collected from DFU patients hospitalized at healthcare institutions in Pakistan. All samples were cultured on three distinct types of media − nutritional agar, McConkey agar, and mannitol salt agar to identify both Gram-negative and Gram-positive bacteria. Biochemical, morphological, and molecular (16 s rRNA) investigations were employed to characterize the bacterial species. Out of the 180 samples collected, Staphylococcus aureus (S. aureus) was isolated from 98 (54 %) samples, Escherichia coli (E. coli) from 75 (41.6 %) samples, S. epidermidis from 20 (11.1 %) samples, and Pseudomonas aeruginosa (P. aeruginosa) from 18 (10 %) samples. Furthermore, PCR amplification confirmed the presence of antibiotic resistance genes in the resistant E. coli and S. aureus isolates. In S. aureus, the most commonly found antibiotic resistance genes were erm(B) and aac(6′) aph (2′) whereas in E. coli the prevalent genes were ampC (tetA) and erm (B). The distributions of many genes associated with drug resistance differed from those documented worldwide. These findings will aid in guiding the empirical use of antibiotics for treating diabetic foot infections, thereby reducing the risk of inappropriate antibiotic use and the development of antibiotic resistance.

Abstract Fernandoa adenophylla, due to the presence of phytochemicals, has various beneficial properties and is used in folk medicine to treat many conditions. This study aimed to isolate indanone derivative from F. adenophylla root heartwood and assess in-vitro anti-inflammatory and anti-diabetic characteristics at varying concentrations. Heat-induced hemolysis and glucose uptake by yeast cells assays were conducted to evaluate these properties. Besides, docking analyses were performed on four molecular targets. These studies were combined with molecular dynamics simulations to elucidate the time-evolving inhibitory effect of selected inhibitors within the active pockets of the target proteins (COX-1 and COX-2). Indanone derivative (10–100 µM) inhibited the lysis of human red blood cells from 9.12 ± 0.75 to 72.82 ± 4.36% and, at 5–100 µM concentrations, it significantly increased the yeast cells’ glucose uptake (5.16 ± 1.28% to 76.59 ± 1.62%). Concluding, the isolated indanone might act as an anti-diabetic agent by interacting with critical amino acid residues of 5′ adenosine monophosphate-activated protein kinase (AMPK), and it showed a binding affinity with anti-inflammatory targets COX-1, COX-2, and TNF-α. Besides, the obtained results may help to consider the indanone derivative isolated from F. adenophylla as a promising candidate for drug delivery, subject to outcomes of further in vivo and clinical studies.

Background and Aim: Dengue infection is a global issue which is caused by insect transmitted, positive sense single-stranded RNA dengue virus (DENV). Around 50 million cases of dengue infection is being reported per year whereas population at risk of dengue of infection reaches about 2.5 billion in the tropical and subtropical regions of the world. The present study aimed to develop global consensus sequence of dengue NS1 protein and modelling interaction of NS1 with various host proteins of different cellular pathways. Methods: Serotype specific consensus sequences of Dengue NS1 were generated using CLC-Work Bench software. The Consensus sequences of NS1 and Cellular proteins were modelled using Protein Model Portal (PMP). Comparative interaction of NS1 of various dengue serotypes were analyzed by means of Haddock server. The biomolecular complexes of dengue NS1 and various host proteins (PTBP1, NF-kB, TRAF6, PAIP1, SRFBP1, FGB, TCF7L2 and EIF4G1) thus formed were evaluated for interacting residues through Protein Interaction Calculator (PIC). Results: The serotype-specific consensus sequences revealed high degree of conservation among the various NS1 domains of different isolates of same serotype but is more heterogeneous among different serotypes. The docking results demonstrated that most of the host proteins including (PTBP1, NF-kB, TRAF6, PAIP1, SRFBP1, FGB, TCF7L2 and EIF4G1) have comparable affinity for the NS1 of different serotypes despite considerable degree of variability among the serotypes. Analysis of interactive residues demonstrated involvement of different domains of NS1 for interaction with host partners even within the NS1 of different serotypes for a particular host protein. Conclusion: The in silico study revealed that various NS1 domains of different isolates were relatively conserved among different serotypes but highly heterogeneous from serotype to serotypes. The Wing domain of NS1 protein plays a vital role in interaction with the host proteins.

Abstract Serious human health impacts have been observed worldwide due to several life-threatening diseases such as cancer, candidiasis, hepatic coma, and gastritis etc. Exploration of nature for the treatment of such fatal diseases is an area of immense interest for the scientific community. Based on this idea, the genus Aspergillus was selected to discover its hidden therapeutic potential. The genus Aspergillus is known to possess several biologically active compounds. The current research aimed to assess the biological and pharmacological potency of the extracts of less-studied Aspergillus ficuum (FCBP-DNA-1266) (A. ficuum) employing experimental and bioinformatics approaches. The disc diffusion method was used for the antifungal investigation, and the MTT assay was performed to assess the anticancer effects. Mice were employed as an in vivo model to evaluate the antispasmodic effects. A standard spectrophotometric technique was applied to gauge the urease inhibitory activity. The antifungal studies indicate that both n-hexane and ethyl acetate extracts were significantly active against Candida albicans (C. albicans) with their zone of inhibitions (ZOI) values reported as 19 ± 1.06 mm and 25 ± 0.55 mm, respectively at a dose of 30 µg.mL−1. In vitro cytotoxicity assay against HeLa, fibroblast 3T3, prostate PC3, and breast MCF-7 cancer cell lines was performed. The ethyl acetate extract of A. ficuum was found to be significantly active against MCF-7 with its IC50 value of 43.88 µg.mL−1. However, no substantial effects on the percent cell death of HeLa cancer cell lines were observed. In addition, the A. ficuum extracts also inhibited the urease enzyme compared to standard thiourea. The antispasmodic activity of A. ficuum extract was assessed by an in vivo model and the results demonstrated promising activity at 150 mg.kg−1. Molecular docking results also supported the antifungal, anticancer, and antiurease potency of A. ficuum extract. Overall, the results display promising aspects of A. ficuum extract as a future pharmacological source.

Objective: Traditionally, Olea ferruginea Royle (Oleaceae) has been used as a painkiller and antidiabetic in various ailments. To provide a scientific background to this folklore the current study was designed to anti-inflammatory and antidiabetic effects of one of the isolated compound from this plant. Methods: Ferruginan A was isolated from the ethyl acetate extract of Olea ferruginea bark. This isolated molecule was subjected to in-vitro anti-inflammatory and antidiabetic effects using HRBCs and glucose uptake tests. The compound was also tested for molecular docking and ADMET study. Results: Regarding the anti-inflammatory effect, the tested compound demonstrated a 69.82 % inhibition at a concentration of 100 µg/mL, while the Ferruginan A (100 µl/mL) increased the uptake of glucose (3.79–71.86 %) in the yeast cell. Similarly, the zone of inhibition values of Ferruginan A (24.98 mm) against Escherichia coli were found to be comparable to standard (Imipenem: 31.09 mm). The mechanism of antidiabetic and anti-inflammatory effects was explored by using docking simulations performed on four molecular targets related to diabetes and inflammation. The results showed that the isolated compound may act as an antidiabetic agent by inhibiting the 5′ Adenosine monophosphate-activated protein kinase (AMPK). While it also showed inhibition of anti-inflammatory targets COX-1, COX-2, and Tumor necrosis factor alpha (TNF-α). The ADMET prediction study revealed that isolated compound possesses favorable ADMET profile. Conclusion: It was concluded that Ferruginan A might be a significant anti-inflammatory and antidiabetic molecule.

Medicinal plants are the main source of active chemical constituents responsible for curing or mitigating various ailments. To discover new, safe, and effective drug candidates the isolation and screening of natural products are essential. In the current research work, lapachol was isolated from Fernandoa adenophylla, which was evaluated for anti-inflammatory effect followed by molecular docking. The isolated compound was tested for anti-inflammatory effects using in vitro (HRBC assay) and in vivo (xylene-induced ear edema) experimental models. Various concentrations of lapachol demonstrated anti-inflammatory effects with a percent potential of 77.96 at 100 μM. Different concentrations of Lapachol demonstrated a dose-dependent anti-edematous effect with a maximum percent effect of 77.9 % at a higher dose. The histopathological study revealed that the application of xylene led to a significant increase in ear thickness, along with clear signs of ear edema and infiltration of inflammatory cells, as well as epidermal hyperplasia of the dermis when compared to the control group. However, treatment with the investigated compound showed a significant reduction in ear thickness and pathological differences comparable to those observed in the group treated with diclofenac. Density functional theory calculations are accomplished to gain insight into structural and spectroscopic properties. Geometry optimization, FMO, and MEP analyses are performed. Overall, the molecular docking results indicate that lapachol has potential as a COX inhibitor by binding to the active sites of both COX-1 and COX-2 enzymes.

Rhizoctonia solani (RS) is a pathogenic fungus that affects maize (Zea mays L.) plants and causes banded leaf and sheath blight (BLSB) with severe consequences leading to significant economic losses. Contrarily, rhizobacteria produce numerous volatile organic compounds (VOCs) that help in devising the environment-friendly mechanism for promoting plant growth and stress alleviation without having physical contact with plants. In the present study, 15 rhizobacterial strains were tested for their antagonism against RS. The antagonistic potential of VOCs of the tested plant growth-promoting rhizobacteria (PGPR) strains ranged from 50% to 80% as compared to the control (without PGPR). Among these 15 strains, the maximum (80%) antagonistic activity was exhibited by Pseudomonas pseudoalcaligenes SRM-16. Thus, the potential of VOCs produced by P. pseudoalcaligenes SRM-16 to alleviate the BLSB disease in maize was evaluated. A pot experiment was conducted under greenhouse conditions to observe the effect of VOCs on disease resistance of BLSB-infected seedlings. Overall, maize seedlings exposed to VOCs showed a significant increase in disease resistance as indicated by a reduced disease score than that of unexposed infected plants. The VOCs-exposed maize exhibited lower (11.6%) disease incidence compared to the non-inoculated maize (14.1%). Moreover, plants exposed to VOCs displayed visible improvements in biomass, photosynthetic pigments, osmoregulation, and plant antioxidant and defense enzyme activities compared to the healthy but unexposed seedlings. Simultaneous application of RS and VOCs enhanced superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), phenylalanine ammonia lyase (PAL), ascorbate peroxidase (APX), and polyphenol oxidase (PPO) activities by 96.7%, 266.6%, 313.7%, 246.6%, 307%, and 149.7%, respectively, in the roots and by 81.6%, 246.4%, 269.5%, 269.6%, 329%, and 137.6%, respectively, in the shoots, relative to those of the control plants. The binding affinity of the VOCs (2-pentylfuran, 2,3-butanediol, and dimethyl disulfide) with CRZ1 and S9 protein receptors of RS was assessed by deploying in silico methods. Overall, 2-pentylfuran exhibited a binding affinity with both the selected receptors of RS, while 2,3-butanediol and dimethyl disulfide were able to bind S9 protein only. Hence, it can be deduced that S9 protein receptors are more likely the target RS receptors of bacterial VOCs to inhibit the proliferation of RS.

Abstract Background Recently, numerous novel bioactive fungal metabolites have been identified that possess broad therapeutic activities including anti-inflammatory, antibiotic, antioxidant, and antitumor. The fungal mycochemicals as well as extracts have increased the interest of the scientific community in drug discovery research through a combination approach such as, molecular metabolic, pharmacological and computational techniques. Therefore, the natural fungus Aspergillus ficuum (A. ficuum) (FCBP-DNA-1266) was selected for metabolic and pharmacological profiling in this study. Results The metabolic profile of A. ficuum was explored for the first time and revealed the presence of bioactive compounds such as choline sulfate, noruron, hydroxyvittatine, aurasperone D, cetrimonium, kurilensoside, heneicosane, nonadecane and eicosane. Similarly, a pharmacological screen of A. ficuum was performed for the first time in in vivo and in vitro models. Interestingly, both the ethyl acetate and n-hexane fractions of A. ficuum were found to be more active against Bacillus subtilis among five tested bacteria with their zone of inhibition (ZOI) values of 21.00 mm ±1.00 and 23.00 mm ±1.00, at a concentration of 150 μgmL-1 respectively. Similarly, a significant decrease (P

Background Penicillium produces a wide range of structurally diverse metabolites with significant pharmacological impacts in medicine and agriculture. For the first time, a complete metabolome of Penicillium claviforme (P. claviforme) (FBP-DNA-1205) was studied alongside pharmacological research in this study.Methods The metabolic profile of P. claviforme fermented on Potato Dextrose Broth (PDB) was investigated in this work. The complete metabolomics studies of fungus were performed using GC-MS and LC-MS-QTOF techniques. An in vitro model was utilised to study the cytotoxic and antioxidant activities, while an in vivo model was employed to investigate the antinociceptive and acute toxicity activities. Molecular Operating Environment (MOE) software was used for molecular docking analysis.Results GC-MS study showed the presence of alkanes, fatty acids, esters, azo and alcoholic compounds. Maculosin, obtain, phalluside, quinoline, 4,4’-diaminostilbene, funaltrexamine, amobarbital, and fraxetin were among the secondary metabolites identified using the LC-MS-QTOF technique. The n-hexane fraction of P. claviforme displayed significant cytotoxic activity in vitro, with an LD50 value of 92.22 µgml−1. The antinociceptive effects in vivo were dose-dependent significantly (p

This paper aims to provide a quick review to jump-start the research in the field of text mining where Machine Learning (ML) algorithms have been used and several accomplishments have been reported by the research community. There are different categories of text mining, and the implementation of ML algorithms and techniques have been supported in the literature to give promising results. However, in this area of study, most of the research activities in terms of time and efforts are consumed during the initial stages where implementations and experiments are carried out to evaluate various combinations. The accomplishments in this field can be further advanced by presenting early investigations concisely and analytically. Thus, the benefits of this paper are threefold: first, it will provide a platform for the new researchers to start quickly with a shorter literature review and knowing more precisely about the combinations of text mining and ML; secondly, clear analysis has been presented about the text mining categories where the performance of ML algorithms have been reported successful; and lastly, the problems have been identified for which the algorithms were used in various studies. This will enable the new researchers to directly target the problem instead of implementing the existing techniques. With the help of well-structured questions, the results are more analytical and present multidimensional views to this research issue. Main findings include that ML has been widely used in document classification and Support Vector Machine (SVM) is the most successful algorithm reported.

Summary: Background: The hormonal profile varies considerably with age, gender, ethnicity, diet or physiological state of an individual. Limited population-specific studies have studied the variations in hormonal parameters among apparently healthy women. We aimed to analyse the biological reference interval for various hormonal parameters in the reproductive-aged healthy Indian women. Methods: Out of 3877 participants that were clinically evaluated, 1441 subjects were subjected to laboratory investigations. All participants underwent a detailed clinical, biochemical and hormonal profiling. The hormone analysis was carried out at a single centre using a uniform methodology. Among the participants evaluated for biochemical and hormonal parameters, subjects that presented any abnormal profile or had incomplete investigations (n = 593) were excluded for further analysis. Findings: The mean age (±SD) of the subjects retained in the final analysis (n = 848) was 29.9 (±6.3) years. In the present study, the biological reference interval (2.5th–97.5th centile) observed were: serum T4: μg/dL (5.23–12.31), TSH: μg/mL (0.52–4.16) and serum prolactin: ng/mL (5.13–37.35), LH: mIU/mL (2.75–20.68), FSH: mIU/mL 2.59–15.12), serum total testosterone: ng/mL (0.06–0.68), fasting insulin: mIU/mL (1.92–39.72), morning cortisol: μg/dL (4.71–19.64), DHEAS:μg/dL (50.61–342.6) and SHBG: nmol/L (21.37–117.54). Unlike T4, TSH, LH, and E2, the biological reference interval for prolactin, FSH, testosterone, C-peptide insulin and DHEAS varied when the subjects were stratified by age (p

Abstract Background Organic cation transporter 1 primarily governs the action of metformin in the liver. There are considerable inter-individual variations in metformin response. In light of this, it is crucial to obtain a greater understanding of the influence of OCT1 expression or polymorphism in the context of variable responses elicited by metformin treatment. Results We observed that the variable response to metformin in the responders and non-responders is independent of isoform variation and mRNA expression of OCT-1. We also observed an insignificant difference in the serum metformin levels of the patient groups. Further, molecular docking provided us with an insight into the hotspot regions of OCT-1 for metformin binding. Genotyping of these regions revealed SNPs 156T>C and 1222A>G in both the groups, while as 181C>T and 1201G>A were found only in non-responders. The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity. Conclusion Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders.

Background: The aim of the current study was to investigate the anticancer potential of bioactive compounds isolated from the leaves of Olea ferruginea (O. ferruginea). Lignans from O. ferruginea were previously described to possess antibacterial, antileishmanial, and antioxidant properties. Nevertheless, the antiproliferative activity of cycloolivil (1), ferruginan (2), and ferruginan A (3) have not been investigated in depth. Methods: The compounds were isolated from the ethyl acetate fraction of the leaves extract of O. ferruginea. The isolated molecules were evaluated for their anticancer activity against U-87 MG malignant glioma cells. In parallel, molecular docking studies were also performed to investigate the interaction of the compounds with a duplex DNA sequence and epidermal growth factor receptor (EGFR). Results: In vitro tests showed that all three compounds inhibit U-87 MG malignant glioma cell proliferation dose-dependently in the µM range, and ferruginan A (3) was highlighted as the most promising compound of the set. Molecular docking studies showed that the compounds could interfere with double stranded DNA possessing a cisplatin 1,2-d(GpG) intrastrand cross-link and EGFR. Conclusions: Overall, the findings suggest that the tested compounds from O. ferruginea may represent a starting point for the identification of novel tools to inhibit glioma cell proliferation.

Background: Maturity onset diabetes of young (MODY) is considered to be the most underdiagnosed condition. The correct diagnosis of MODY has a definite bearing on the outcome and clinical course of the disease. We aim to determine the prevalence and clinical profile of MODY among young diabetic patients attending at Department of Endocrinology, a tertiary care institute in North India. Methods: It was a cross-sectional study involving all consecutive consenting patients with diabetes and age of onset ≤35 years. A total of 1,094 patients were included in this study, of whom 858 were having age of onset of diabetes 0.6 ng/mL were subjected to the Ala98 Val polymorphism (SNP) in hepatocyte nuclear factor (HNF) 1α gene. Results: The prevalence of MODY among the study cohort as per clinical criteria was found to be 7.7%. Males constituted the majority of patients (male vs female, 56% vs. 44%; P < 0.001). The patients with MODY were younger (p < 0.001), leaner (p < 0.001), had younger age at onset of diabetes mellitus (p < 0.001), and lower frequency of features of insulin resistance in the form of skin tags and acanthosis nigricans. Among the 40 patients who were subjected to Ala98Val polymorphism of HNF1α gene (MODY 3), the mutant genotype was seen in 20 (50%) patients. Conclusion: We report a higher prevalence of MODY in our young diabetic patients. A high index of suspicion is required to diagnose MODY as misdiagnosis and inappropriate treatment may have a significant impact on quality-of-life (QOL) with increased cost and unnecessary treatment with insulin.

Abstract. 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.

Islam has allowed breastfeeding; feeding a child with the milk of a woman other than its mother is also allowed. Breast feeding of a woman other than mother may be needed for many reasons, for example, when child’s mother dies or she is not producing sufficient milk for child's nutrition, or she is busy with work, or she does not have sufficient time to breastfeed her child. There is the chance that mother may go out for several days, likewise there are many other reasons which prove that she is unable to breastfeed her child. In such cases, Islam allows a child to be nursed by any other woman so that child can be nourished properly. According to this, the Islamic Shariah commandments are proven; for example, a mother-son relationship is established between a breastfeeding woman and a breastfeed child, due to which all the relationships connected with the breastfeeding woman are associated to this child as well. On the one hand, a relationship of un-marriageability is established between them, due to which marital relation between them is illegal and veil orders are also lifted in front of such child. Many Muslims are unaware of the results of Riza'at i.e. breastfeeding along with its conditions that when Riza't is proven and when it is not proven, what are the conditions for its proof and other related things to Riza'at. They are also oblivious to many other problems, due to which many social problems arise, especially the problems of marriage. Therefore, in this paper, the problems related to breastfeeding of a child other than mother are researched. Most of the jurists are in agreement in most of the issues, but in some issues they have different point of views, so in this paper, the viewpoints of different jurists and their arguments have been researched and analyzed. In this regard, mainly the Qur'an and Sunnah are the primary sources. While various books of jurists and related material have also been taken from five school of thoughts, ie Hanafiah, Shafaiah, Malikiah, Hanbliah and Shiah.

Abstract 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.

Bisphenol A (BPA), an alkylphenolic compound, is one of the most polluting and hazardous organic chemicals. Its routine detection is, however, still rather expensive due to high-cost equipment. In this context, we applied the effect caused by BPA to the optical properties of surfactant-stabilized silver nanoparticles further modified with the use of ammonia (AgNP-NH3) to develop a simple and quantitative approach for BPA determination. The experimental conditions of the AgNP-NH3 probe were adjusted to establish a stable and sensitive response toward BPA in aqueous media. The use of probe dispersion measured at a wavelength of 403 nm enabled a limit of detection of 2.0 nmol L−1 (0.5 ng mL−1), with a linear response as a function of a concentration of BPA ranging from 10 to 120 nmol L−1 (from 2.2 to 27 ng mL−1). The use of vortex-assisted liquid–liquid microextraction ensured the application of selective determination to real tap and stream water samples, with recoveries ranging from 85.0 to 111%. The protocol developed herein is simple, sensitive, and selective, does not require the use of toxic labeling agents, and can be easily adapted for the routine analysis of BPA in different real samples.

Recent developments in clinical patient-based personalized genomics explored a variety of biomarkers for diagnosis, prognosis, and therapy in breast invasive carcinoma (BRIC). BRCA1 mutations mediated a catastrophic situation for a damage-repairing apparatus that induced malignant transformation of breast tissue. To identify an association between BRCA1 regulatory behavior and the pathway-level proteome for determining drug discovery channels, here we developed a computational scheme for BRCA1 pathway dataset retrieval from PathCards: PATHWAY UNIFICATION DATABASE (1,073 superpaths of 3,215 human pathways from 12 sources), BRCA1 pathway regulation analysis from cBioPortal for Cancer Genomics (more than 40 datasets of above 13,000 cancer samples), and BRC1 network construction from STRING v11.0 database (24,584,628 proteins of 5,090 organisms). Our study reveals about 700 alterations of 64 pathway components in 482 BRIC samples, in which there were 422 loss-of-function (LOF) mutations and 278 amplifications. We found 19 members (BRCA1, BRCA2, FANCA, ATM, NBN, SMARCD2, HDAC9, PLK1, SMARCA4, POU2F1, TP53, HDAC2, HLTF, BLM, E2F4, UBC, E2F5, MRE11, and RB1) based on a minimum 2% participation that showed 541 alterations in which there were 193 amplifications and 348 LOF mutations. From 19 components, BRCA1, BRCA2, FANCA, ATM, and TP53 have high-level LOF mutations whereas E2F5, NBN, SMARCD2, and POU2F1 have prominent amplifications. We developed three modules in which the BRCA1 module has 12 members that are involved in damage sensing and repairing processes as hot spots showing overexpression and LOF mutations. This in silico approach uniquely addressed BRCA1 mutations’ influence on BRIC at the pathway proteome level, with module identification as a hub for drug designing. We proposed these proteins as biomarkers for first-class diagnosis and clinical investigations. In the future, BRCA1 pathway-related therapeutic markers are used for further experimental investigations regarding drug development in breast cancer biology.

Metastasis Associated 1 (MTA1) chromatin modifier oncoprotein played a crucial role in both normal and genotoxic stress situations for genome maintenance. To investigates MTA1 regulatory pattern with drug resistance abilities in breast primary carcinoma to advanced invasive stages for identification of cancer adapting defense system. We design rationale in silico pipeline from data retrieval to analysis i.e. gene enrichment analysis performed by GeneCards Version 5.1: THE HUMAN GENE DATABASE (www.genecards.org), UALCAN database (www.ualcan.path.uab.edu) for analyzing MTA1 gene expression and promoter methylation in both breasts normal and cancerous tissue samples, cBioPortal for Cancer Genomics (www.cbioportal.org) database for MTA1 mutation analysis and finally analyzed MTA1 functional association with anticancer drugs in breast malignancy via online CCLE GDSC toolkit (www.public.tableau.com/CCLE_GDSC_Correlations). Our results revealed MTA1 overexpression aggressive behavior in stage II, stage III, TNBC-LAR, TNBC-M, TNBC-UNS, IDC, ILC, and post-menopause events of breast malignancy. MTA1 upregulation strongly promotes primary tumor transformation into invasive metastatic carcinoma by hijacking the host lymphatic system and cytokine signaling in both ductal and glandular breast cancers. MTA1 upregulation in the African-American population invites to design de novo model of cancer cell homeostasis under a reduced supply of vegetable nutrients, local-foreign stress, and replicative capacity for metastasis. MTA1 showed a hypomethylation profile that reflects regulatory strength under stress-mediated situations for higher events of transcription. In drug resistance analysis MTA1 has strong resistance towards 15 anti-cancer drugs that confirmed its previously reported behavior of genotoxic stress adaptation for metastasis. Our in silico evidence invites us to design a comprehensive strategy against MTA1 mediated stress managing proteome. In the future there is an urgent need to explore MTA1 shared stress coped protein networks for early diagnosis and better prognosis.

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.

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.

The efficiency of Cd-tolerant plant growth-promoting bacteria (PGPB), zinc oxide nanoparticles (ZnO NPs), and titanium dioxide nanoparticles (TiO2) in maize growing in Cd-rich conditions was tested in the current study. The best Cd-tolerant strain, Bacillus pumilus, exhibited plant growth stimulation in vivo and in vitro experiments. We determined the toxic concentrations (30 (ppm)) of both NPs for plant growth. B. pumilus, ZnO NPs (20 (ppm)), and TiO2 NPs (10 (ppm)) had a synergistic effect on plant growth promotion in Cd-contaminated soil (120 (ppm)) in a pot experiment. Both alone and in combination, these therapies reduced Cd toxicity, resulting in improved stress metabolism and defense responses. The combined treatments showed increased relative water content, photosynthetic pigments, proline, total sugars, and proteins and significantly reduced lipid peroxidation. Moreover, this combination increased the levels of minerals and antioxidants and reduced Cd bioaccumulation in shoots and roots by 40–60%. Our in silico pipeline presented a novel picture of the participation of ZnO–TiO2 protein interaction in both B. pumilus and maize. These findings provide fresh insights on the use of B. pumilus, ZnO, and TiO2 NPs, both separately and in combination, as a viable and environmentally benign strategy for reducing Cd stress in maize.

Abstract An assay was designed to evaluate the efficacy of each entomopathogenic fungus, Beauveria bassiana, and diatomaceous (DE) and their combinations at concentrations of 1 × 106 and 1 × 108 conidia kg−1 of wheat and 200 and 400 ppm, respectively, on the red flour beetle, Tribolium castaneum (Herbst) (Tenebrionidae: Coleoptera), infesting wheat. Percent mortality of T. castaneum was recorded after 7, 14, and 21 days. Percent mycosis on dead cadavers was assessed after 21 days. Alive adults were removed from plastic jars after 21 days and kept for the next 60 days to assess the progeny production. The results indicated that the highest concentrations of B. bassiana and DE in their combinations were more effective for the virulence and progeny suppression of T. castaneum. Maximum mean percent mortality (88.13%) was recorded by B. bassiana (1 × 108 conidia kg−1 of wheat) and DE (400 ppm) in their combination after a 21-day exposure interval, while a minimum percent mean mortality (10.00%) was recorded by B. bassiana (1 × 106 conidia kg−1 of wheat) alone. The maximum percent mycosis (78.89%) on dead cadavers was recorded at a low concentration rate (1 × 106 conidia/kg) of B. bassiana. Mean progeny adult emergence was the highest (62.67 adults) at the low concentration of B. bassiana alone. Present studies showed that B. bassiana and DE are more effective in combination against T. castaneum on wheat as both substances are advantageous.

This work presents the joint use of Radio Over Fiber and optical chaos to investigate the secure ROF link. Merging the two technologies, optical chaos for physical layer communication security and Radio over Fiber creates new design issues which have been identified and studied in detail in this paper for both analog Radio Frequency/Intermediate Frequency and digitized data. A semiconductor laser diode is driven into chaotic region using direct modulation scheme and RoF signal is added by chaos message masking scheme. The chaotically masked signal is transmitted over an optical communication link to investigate the propagation issues and synchronization of chaos at the receiver. The transmitted chaos is synchronized at the receiver to unmask the signal by using subtraction rule. To investigate the performance of chaotic communication system for Radio over Fiber transmission, the figure of merits like Bit error rate, Quality factor, Eye Opening Penalty and Root-mean-squared phase jitter are studied for digital data and Signal to Noise ratio and Total Harmonic Distortion are studied for analog waveform to address the effects of link length and data rate/message bandwidth.

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

Abstract 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: 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.

Berberine (BBR), a potential bioactive agent, has remarkable health benefits. A substantial amount of research has been conducted to date to establish the anticancer potential of BBR. The present review consolidates salient information concerning the promising anticancer activity of this compound. The therapeutic efficacy of BBR has been reported in several studies regarding colon, breast, pancreatic, liver, oral, bone, cutaneous, prostate, intestine, and thyroid cancers. BBR prevents cancer cell proliferation by inducing apoptosis and controlling the cell cycle as well as autophagy. BBR also hinders tumor cell invasion and metastasis by down-regulating metastasis-related proteins. Moreover, BBR is also beneficial in the early stages of cancer development by lowering epithelial–mesenchymal transition protein expression. Despite its significance as a potentially promising drug candidate, there are currently no pure berberine preparations approved to treat specific ailments. Hence, this review highlights our current comprehensive knowledge of sources, extraction methods, pharmacokinetic, and pharmacodynamic profiles of berberine, as well as the proposed mechanisms of action associated with its anticancer potential. The information presented here will help provide a baseline for researchers, scientists, and drug developers regarding the use of berberine as a promising candidate in treating different types of cancers.

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 < 0.05), while the APOA1 +83 C/T heterozygotes showed an association with cases (p < 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 < 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 (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.

Abstract Background Cytokines have been found to be the important mediators during renal graft outcome. Therefore, we designed this study to investigate the role of recipients’ IL-1 β promoter (−511) and IL-1 β exon-5 (+3954) polymorphisms with the risk of graft outcome. Methodology We enrolled one hundred recipients of living-related renal transplants together with the age and sex matched controls from the healthy population not having any renal abnormality for this study. Genotype frequencies of the IL-1 β promoter (−511) and IL-1 β exon-5 (+3954) were analyzed using PCR-RFLP technique. Results Our results revealed significant differences in the healthy control group and patient group in IL 1β +3954 (p

A numerical study is presented in this paper based on semiconductor laser chaos generation which is being used to hide multi-level data signal, i.e., duo-binary message to take the advantage of secure environment & higher data rates at the same time. Duobinary message is generated by using the combination of duobinary precoder, duobinary generator & RZ/NRZ pulse generator. Laser rate equations are used to model chaos generation through semiconductor laser whereas message is made secured by hiding it through chaos masking scheme. Propagation of chaos hiding the multi-format message is studied for long distance communication model. Synchronization between transmitter & receiver is achieved to obtain the acceptable eye-diagrams & quality factor (Q-factor). Q-factor is function of optical signal to noise ratio (OSNR) that gives a qualitative performance of receiver. It provides the minimum SNR to obtain specific bit error rate of signal. A comparison is made with & without deployment of chaos masking scheme on RZ & NRZ duobinary optical system to observe the penalty in terms of Q-factor. In addition, response of amplifier on chaotic signal due to its nonlinearities is investigated by varying the gain of amplifier.

Background: Methylenetetrahydrofolate reductase (MTHFR) gene is a crucial regulator of folate metabolism and its two prominent polymorphic variants C677T and A1298C lead to decreased MTHFR enzyme activity.Aim of the Study: We planned this case–control study based on numerous studies supporting the association of MTHFR polymorphisms (C677T and A1298C) with CML risk in different ethnic populations. Therefore, the influence of these polymorphisms on CML susceptibility was investigated among Kashmiri population (North India).Materials and Methods: Polymerase chain reaction/restriction fragment length polymorphism (RFLP) technique was employed for genotyping MTHFR C677T and A1298C SNP's in 125 CML patients as against 150 age and gender matched healthy controls.Results: A significant difference was observed in frequency of 677CT genotype between cases and controls [46.4 vs. 27.3% (p = 0.0005)]. Similarly combined 677CT+TT genotype showed significant difference between cases and controls [50.4 vs. 28.6% (p = 0.0002)]. Both MTHFR 677CT and 677CT+TT genotypes imposed greater than 2-fold risk of developing CML (OR = 2.4, 95%CI: 1.46–4.05; OR = 2.5, 95%CI: 1.53–4.16). In case of A1298C SNP, the frequency of 1298AC genotype was higher in controls (64.0%) as compared to CML cases (48.8%) (p = 0.04) and imparted a significant protective role from CML predisposition. Furthermore, haplotype analysis revealed only “677CT/1298AA” haplotype significantly increased the risk of CML predisposition [(p = 0.008) (OR = 3.2, 95% CI: 1.3–7.4)].Conclusion: We conclude that both MTHFR C677T and A1298C polymorphisms may be important genetic modifiers and seem to have a plausible role to confer risk of CML in Kashmiri population, where C677T SNP strongly increases the risk of CML while as A1298C SNP has a protective effect.

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.

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.