A comprehensive Y-STR portrait of Yousafzai’s population

In the current study, 17 Y-Chromosomal short tandem repeats (Y-STRs) included in theAmpFlSTR Y-Filer amplification kit (Applied Biosystems, Foster City, USA) were investigated in 146 unrelated Yousafzai males residing in the Khyber Pakhtunkhwa Province of Pakistan. A total of 94 (89.52%) unique haplotypes were observed. Discrimination capacity was 71.92%. Haplotype diversity ranged from 0.354 (DYS456) to 0.663 (DYS458). Both Rst pairwise analysis and multidimensional scaling plot showed that the genetic structure of the Yousafzais is significantly different from neighbouring populations.

     

Somatic JAK-2 V617F Mutational Analysis in Polycythemia Rubra Vera: a Tertiary Care Center Experience

Background: Polycythemia rubra vera (PV), being a primary polycythemia, is caused by neoplastic proliferation of erythroid, megakaryocytic and granulocytic lineages which result in panmyelosis. PV patients have a somatic acquired mutation in the Janus kinase (JAK2) pathway, rendering cell proliferation independent of the normal regulatory mechanisms that regulate erythropoiesis. The rational of this study was to determine the prevalence of the JAK-2 V617F mutation in Pakistani patients with PV. Materials and Methods: In this cross sectional study, 26 patients with PV were enrolled from January 2010 to December 2014. Patients were diagnosed based on WHO criteria for PV. All were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific PCR. Results: The mean age was 53.49.31 years (range 36-72) and the male to female ratio was 2:1. The frequency of JAK2 V617F positivity in our PV patients was found to be 92.3%. Overall 30.7% of patients were asymptomatic and remaining 69.3% presented with symptomatic disease. The mean hemoglobin was 18.11.9g/dl with the mean hematocrit of 55.68.3%. The mean total leukocyte count was 12.87.1x109/l and the platelet count was 511341.9x109/l. A positive correlation of JAK2 V617F mutation was established with high TLC count (P=0.01). No correlation of JAK2 V617F could be established with age or gender (P>0.05). Conclusions: The JAK2 V617F mutation frequency in our PV patients was similar to those reported internationally. Screening for the mutation in all suspected PV cases could be beneficial in differentiating patients with reactive and clonal erythrocytosis.     

Harmine, a natural beta-carboline alkaloid, upregulates astroglial glutamate transporter expression

Glutamate is the predominant excitatory amino acid neurotransmitter in the mammalian central nervous system (CNS). Glutamate transporter EAAT2/GLT-1 is the physiologically dominant astroglial protein that inactivates synaptic glutamate. Previous studies have shown that EAAT2 dysfunction leads to excessive extracellular glutamate and may contribute to various neurological disorders including amyotrophic lateral sclerosis (ALS). The recent discovery of the neuroprotective properties of ceftriaxone, a beta lactam antibiotic, suggested that increasing EAAT2/GLT-1 gene expression might be beneficial in ALS and other neurological/psychiatric disorders by augmenting astrocytic glutamate uptake. Here we report our efforts to develop a new screening assay for identifying compounds that activate EAAT2 gene expression. We generated fetal derived-human immortalized astroglial cells that are stably expressing a firefly luciferase reporter under the control of the human EAAT2 promoter. When screening a library of 1040 FDA approved compounds and natural products, we identified harmine, a naturally occurring beta-carboline alkaloid, as one of the top hits for activating the EAAT2 promoter. We further tested harmine in our in vitro cell culture systems and confirmed its ability to increase EAAT2/GLT1 gene expression and functional glutamate uptake activity. We next tested its efficacy in both wild type animals and in an ALS animal model of disease and demonstrated that harmine effectively increased GLT-1 protein and glutamate transporter activity in vivo. Our studies provide potential novel neurotherapeutics by modulating the activity of glutamate transporters via gene activation. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.     

New aromatic esters from Galinsoga parviflora

Galinosoates A-C (1-3), new aromatic esters, have been isolated from the n-hexane soluble fraction of Galinsoga parviflora. Their structures were assigned from the spectral data including IR, HR-EI-MS, 1D and 2D NMR.     

Behavioral problems among children living in orphanage facilities of Karachi,Pakistan: comparison of children in an SOS Village with those in conventional orphanages

Purpose  

This study compared the behavioral problems of children living in an SOS Village, which attempts to provide a family setup for its children, with those living in conventional orphanages.     

Epidemiologic profile of pediatric brain tumors in Morocco

Introduction  

Brain tumors are the most common solid tumors diagnosed among children below 15 years worldwide. However, little is known about the profile of pediatric brain tumors in Africa. The purpose of this study was to further elaborate the epidemiological profile of pediatric brain tumors in Africa, specifically Morocco.     

A probit- log- skew-normal mixture model for repeated measures data with excess zeros,with application to a cohort study of paediatric respiratory symptoms

Background  

A zero-inflated continuous outcome is characterized by occurrence of "excess" zeros that more than a single distribution can explain, with the positive observations forming a skewed distribution. Mixture models are employed for regression analysis of zero-inflated data. Moreover, for repeated measures zero-inflated data the clustering structure should also be modeled for an adequate analysis.     

The changing epidemiology pattern and frequency distribution of hepatitis C virus in Pakistan

Information regarding the changing pattern in hepatitis C virus (HCV) genotypes/subtypes and resulting disease outcome is not well known. The specific objective of this study was to find out the frequency distribution of HCV genotypes and changing pattern of various HCV genotypes overtime in well-characterized Pakistani HCV isolates. The genotype distribution of HCV from all the four provinces of Pakistan was tracked for a period of 10 years (2000–2009) on total 20,552 consecutive anti-HCV and HCV RNA positive patients sample using type-specific genotyping assay. Of these, 16,891 (82.2%) samples were successfully genotyped. Of these 11,189 (54.4%) were males and 9363 (45.55%) were females. Of the successfully genotyped samples, 12,537 (74.2%) were with 3a, 1834 (10.9%) with 3b, 50 (0.24%) with 3c, 678 (3.3%) with 1a, 170 (0.83%) with 1b, 49 (0.24%) with 1c, 431 (2.1%) with 2a, 48 (0.23%) with 2b, 3 (0.01%) with 2c, 13 (0.06%) with 5a, 12 (0.06%) with 6a, 101 (0.49%) with 4, and 965 (4.7%) were with mixed-genotype infection. A changing pattern of HCV genotypes prevalence was observed in Pakistan overtime, with an increase in the relative proportion of genotype 3a and mixed genotypes and a decrease of genotypes 3b, 2b, 4, 5a and 2a. This changed HCV genotype pattern might have direct impact on HCV disease outcome and new therapeutic strategies may be needed.     

Beta-Sitosterol: A Promising but Orphan Nutraceutical to Fight Against Cancer

All the currently available cancer therapeutic options are expensive but none of them are safe. However, traditional plant-derived medicines or compounds are relatively safe. One widely known such compound is beta-sitosterol (BS), a plant derived nutrient with anticancer properties against breast cancer, prostate cancer, colon cancer, lung cancer, stomach cancer, ovarian cancer, and leukemia. Studies have shown that BS interfere with multiple cell signaling pathways, including cell cycle, apoptosis, proliferation, survival, invasion, angiogenesis, metastasis and inflammation. Most of the studies are incomplete partly due to the fact that BS is relatively less potent. But the fact that it is generally considered as nontoxic, the opposite of all currently available cancer chemo-therapeutics, is missed by almost all research communities. To offset the lower efficacy of BS, designing BS delivery for “cancer cell specific” therapy hold huge potential. Delivery of BS through liposome is one of such demonstrations that has shown to be highly promising. But further research did not progress neither in the field of drug delivery of BS nor in the field on how BS mediated anticancer activities could be improved, thus making BS an orphan nutraceutical. Therefore, extensive research with BS as potent anticancer nutraceutical is highly recommended.