VITAMIN D RECEPTOR (VDR) GENE POLYMORPHISM AND MATERNAL VITAMIN D DEFICIENCY IN INDIAN WOMEN WITH PRETERM BIRTH (PTB)

  Objective: Preterm birth (PTB) is the leading cause of high infant mortality and long-term disability in young children worldwide. Array of adverse maternal and fetal outcomes linked with vitamin D level and its associated vitamin D receptor (VDR) gene. We undertook this study to investigate the association between VDR gene polymorphism with vitamin D deficiency and PTB in West Indian pregnant women.Methods: A total of 72 women with PTB and 138 healthy mothers with uncomplicated normal delivery were selected from different regions of Gujarat, India. FokI and TaqI single nucleotide polymorphism (SNP) of VDR gene determined by polymerase chain reaction and restriction fragment length polymorphism. Vitamin D level was determined using enzyme-linked immunosorbent assay.Result: ff genotype (29.17% vs. 10.87%, p=0.002) and f allele (49.31% vs. 35.51%, p=0.006) frequency distributions of VDR FokI showed significantly (odds ratio=0.566, 95% confidence interval=0.368-0.870, p=0.006) higher in women with preterm delivery than in control full term group. Genotype frequency of VDR TaqI showed no significant difference between preterm group and control.Conclusion: These results confirmed that women carrying ff genotype of FokI gene had significantly higher risk for vitamin D deficiency which enhances the risk of prematurity than women carrying FF genotype in West Indian women

Fertility preservation in non-seminomatous germ cell tumor: a case report

Testicular germ cell tumors (TGCTs) are the most common malignancy in young men in their peak fertility years. It can intrinsically and permanently affect fertility potential of an individual. Clinicians are advised to offer Fertility Preservation before initiating the treatment. We present one such case of presence of Neoplasm in testis, where semen was cryopreserved before operating it for fertility preservation and biological pregnancy was achieved. On further investigations, presence of neoplasm on left testis was diagnosed. However, neoplasms of the testes are unique in that way they affect men at a young age and also have a high survival rates. Cryopreservation of ejaculated or surgically retrieved sperm is currently the only established method of fertility preservation for post-pubertal man. The incidence as well as rates for testicular cancers have remained relatively low and if presented early on, can be cured and has good survival rates. Fertility awareness must be raised amongst the oncologist, gynecologist and patients

Acute kidney injury requiring dialysis in obstetric patients: management and clinical outcome in case series of 30 patients in a tertiary care centre

Background: Acute Kidney Injury is a common medical problem affecting approximately 5% of all hospitalized and 30% of critically ill patients. The incidence in obstetric patients ranges from 1 in 2000 to 1 in 25000 pregnancies. In India till date, the impact of AKI on fetomaternal outcome and pertaining therapeutic interventions is only sparsely studied.Methods: It is a retrospective cross-sectional study. All obstetric patients with AKI on dialysis, admitted to Shree Krishna Hospital, a tertiary care hospital in Karamsad village in Gujarat from January 2013 to August 2015. Multivariate statistical analysis of clinical and laboratory parameters was performed using SPSS program to obtain the results.Results: The incidence of dialysis was 1.6%. HELLP syndrome and pre-eclampsia (80%) was found to be the most common etiology of AKI followed by Congestive cardiac failure (34.5%), hemorrhage and sepsis in 30% resp. All patients were admitted to ICU care. No significant difference was found between SAP II and SOFA monitoring system. Mechanical ventilation was done to support 53.3% and inotropic support was needed by 56.7% patients. According to the RIFLE criteria, majority of the patients fall under risk category followed by injury. 18% of the patients developed End Stage Renal Disease.Conclusions: In view of the multifaceted etiologies and complexity of management of AKI, a multi-disciplinary approach involving nephrologist, intensivists, obstetricians and neonatologists is extremely important

Pre-implantation genetic testing: a retrospective observational study of 13 cases of various genetic diseases successfully detected and managed at an IVF centre

Pre-implantation genetic testing (PGT) is an advanced form of prenatal genetic testing that is done as a part of ART cycles. The purpose of PGT is to identify genetically normal embryos in a given cohort, in order to select the most desirable embryos for implantation. With the gaining popularity of day 5 trophectoderms biopsy over day 3 blastomere biopsy, the role of PGT has become more clinically significant. To report the data of 13 couples, with diagnosed genetic condition and having risk of transmitting this condition to their offspring’s, who underwent Pre-implantation genetic diagnostics (PGT M/SR). PGT was performed in 13 couples with various rare chromosomal conditions like Hereditary Inclusion body myopathy, Col4a1 gene mutation etc at our Infertility Centre from January 2016 to January 2020. The clinical data of all these patients was reviewed and is reported in our study. A total of 193 oocytes were retrieved and 158 oocytes were fertilized by ICSI. 62 blastocysts were obtained and 55 blastocysts were biopsied for analysis. Among the 35 normal embryos, 17 embryos were transferred. 11 clinical pregnancies were established resulting in 8, disease free, live births. PGT (M/SR) is an effective molecular diagnostic test, that is a ray of hope for many genetically affected couples, as its prevents the transmission of their unwanted genetic condition to their offspring’s

Analysis of baseline parameters in the HALT polycystic kidney disease trials

HALT PKD consists of two ongoing randomized trials with the largest cohort of systematically studied patients with autosomal dominant polycystic kidney disease to date. Study A will compare combined treatment with an angiotensin-converting inhibitor and receptor blocker to inhibitor alone and standard compared with low blood pressure targets in 558 early-stage disease patients with an eGFR over 60ml/min per 1.73m2. Study B will compare inhibitor-blocker treatment to the inhibitor alone in 486 late-stage patients with eGFR 25–60ml/min per 1.73m2. We used correlation and multiple regression cross-sectional analyses to determine associations of baseline parameters with total kidney, liver, or liver cyst volumes measured by MRI in Study A and eGFR in both studies. Lower eGFR and higher natural log-transformed urine albumin excretion were independently associated with a larger natural log–transformed total kidney volume adjusted for height (ln(HtTKV)). Higher body surface area was independently associated with a higher ln(HtTKV) and lower eGFR. Men had larger height-adjusted total kidney volume and smaller liver cyst volumes than women. A weak correlation was found between the ln(HtTKV) and natural log–transformed total liver volume adjusted for height or natural log liver cyst volume in women only. Women had higher urine aldosterone excretion and lower plasma potassium. Thus, our analysis (1) confirms a strong association between renal volume and functional parameters, (2) shows that gender and other factors differentially affect the development of polycystic disease in the kidney and liver, and (3) suggests an association between anthropomorphic measures reflecting prenatal and/or postnatal growth and disease severity

Anthrax Lethal Toxin Disrupts Intestinal Barrier Function and Causes Systemic Infections with Enteric Bacteria

A variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (MAPK) signaling pathways, including Bacillus anthracis. Anthrax lethal toxin (LT) has specific proteolytic activity against the upstream regulators of MAPKs, the MAPK kinases (MKKs). Using a murine model of intoxication, we show that LT causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. This pathology correlates with an LT-dependent blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. C57BL/6J mice treated with intravenous LT nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. LT-dependent intestinal pathology depends upon its proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics, indicating that it is both a cause and an effect of infection. These findings indicate that targeting of MAPK signaling pathways by anthrax LT compromises the structural integrity of the mucosal layer, serving to undermine the effectiveness of the intestinal barrier. Combined with the well-described immunosuppressive effects of LT, this disruption of the intestinal barrier provides a potential mechanism for host invasion via the enteric route, a common portal of entry during the natural infection cycle of Bacillus anthracis

Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington's disease

An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington’s disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntington’s disease. For this purpose, we analysed data from Track-HD, a multi-centre longitudinal study in Huntington’s disease gene carriers and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared with non-carriers, in agreement with its role in somatic instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, i.e. those who were better educated, had higher verbal intelligence and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntington’s disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non-carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than for non-carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntington’s disease and their effect on brain structure

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

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