In Vitro Study of MefenamateStarch as Drug Delivery System

Mefenamic acid was esterified with starchwith[1:1] Molar ratio, as drug substituted with natural polymer, to prolongthe period of hydrolysis of drug polymer with other advantages. The new prodrug starch was characterized by FT-IR and UV-Visible and 1H-NMR spectroscopies. The physical properties were studied and controlled drug release was studied in different pH values at 37oC. The stability of drug was carried out by measuring the absorbance of mefenamic starch which hydrolyzed in HCl solution of pH 1.1 (artificial gastric fluid) and phosphate buffer of pH 7.4 (simulating intestinal fluid SIF) at 37oC for several days. The thermal analysis such as DSC was studied

Antigenic Detection of Salmonella Infection among Pediatric Patients with Acute Gastroenteritis

Background: Diarrheal diseases are one of the social problems in developing countries. The pathogens commonly associated with childhood diarrhea are Salmonella, Clostridium difficile, Shigella, Yersinia and Escherichia coli but the highest attack rate for salmonellosis in infancy. Objective: The aim of the study was to evaluate the presence of Salmonella antigen in acute gastroenteritis in children admitted to a pediatric hospital. Material and Methods: The study was performed on freshly collected stool samples among 94 acute diarrheal children below two years admitted to AL-Khadymia and AL-Elweya pediatric hospitals from May 2015 to January 2016. A questionnaire was completed for each patient’s name, age, gender, clinical data like fever, nausea, vomiting, and abdominal pain. The criteria included hemorrhagic fresh stool sample in addition to containing parasite agent. Fresh stool samples were tested by immunochromatographic assay for antigenic detection of Salmonella. Results: Salmonella antigen identified in five stool samples one for male and four for females. All pediatric patients show fever, vomiting and abdominal pain, while the stool consistency distributed to 75.5% watery and 24.5% loosely. Stool samples show 69.1% with blood and 39.9% without blood, 16.9% with pus and 83.1% without pus, 83% with mucous and 17% without mucous. Four cases with giardiasis and 24 cases with entamebiasis and 14 cases with cyst of E. histolytica or G. lamblia in addition to absence the parasites ova in all stool samples. Conclusion: Salmonella antigen present in five stool samples, all the patients show vomiting, fever, abdominal pain, 65 cases with blood in comparison with, 29 without blood 15 cases with pus in comparison with 79 without pus. 78 cases with mucous in comparison with, 16 without mucous, four cases with goddesses and 24 cases with entamebiasis, 14 cases with cyst of E. histolytica or G. lamblia in addition to absence the parasites ova in all stool samples

Geometry and kinematics for a spherical-base integrated parallel mechanism

Parallel mechanisms, in general, have a rigid base and a moving platform connected by several limbs. For achieving higher mobility and dexterity, more degrees of freedom are introduced to the limbs. However, very few researchers focus on changing the design of the rigid base and making it foldable and reconfigurable to improve the performance of the mechanism. Inspired by manipulating an object with a metamorphic robotic hand, this paper presents for the first time a parallel mechanism with a reconfigurable base. This novel spherical-base integrated parallel mechanism has an enlarged workspace compared with traditional parallel manipulators. Evolution and structure of the proposed parallel mechanism is introduced and the geometric constraint of the mechanism is investigated based on mechanism decomposition. Further, kinematics of the proposed mechanism is reduced to the solution of a univariate polynomial of degree 8. Moreover, screw theory based Jacobian is presented followed by the velocity analysis of the mechanism

Mechanical properties of cotton fabric reinforced geopolymer composites at 200-1000 °C

Geopolymer composites containing woven cotton fabric (0–8.3 wt%) were fabricated using the hand lay-up technique, and were exposed to elevated temperatures of 200 °C, 400 °C, 600 °C, 800 °C and 1000 °C. With an increase in temperature, the geopolymer composites exhibited a reduction in compressive strength, flexural strength and fracture toughness. When heated above 600 °C, the composites exhibited a significant reduction in mechanical properties. They also exhibited brittle behavior due to severe degradation of cotton fibres and the creation of additional porosity in the composites. Microstructural images verified the existence of voids and small channels in the composites due to fibre degradation

The Chromatin Modifier MSK1/2 Suppresses Endocrine Cell Fates during Mouse Pancreatic Development

Type I diabetes is caused by loss of insulin-secreting beta cells. To identify novel, pharmacologically-targetable histone-modifying proteins that enhance beta cell production from pancreatic progenitors, we performed a screen for histone modifications induced by signal transduction pathways at key pancreatic genes. The screen led us to investigate the temporal dynamics of ser-28 phosphorylated histone H3 (H3S28ph) and its upstream kinases, MSK1 and MSK2 (MSK1/2). H3S28ph and MSK1/2 were enriched at the key endocrine and acinar promoters in E12.5 multipotent pancreatic progenitors. Pharmacological inhibition of MSK1/2 in embryonic pancreatic explants promoted the specification of endocrine fates, including the beta-cell lineage, while depleting acinar fates. Germline knockout of both Msk isoforms caused enhancement of alpha cells and a reduction in acinar differentiation, while monoallelic loss of Msk1 promoted beta cell mass. Our screen of chromatin state dynamics can be applied to other developmental contexts to reveal new pathways and approaches to modulate cell fates

Partial Loss of Ataxin-1 Function Contributes to Transcriptional Dysregulation in Spinocerebellar Ataxia Type 1 Pathogenesis

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a CAG repeat that encodes a polyglutamine tract in ATAXIN1 (ATXN1). Molecular and genetic data indicate that SCA1 is mainly caused by a gain-of-function mechanism. However, deletion of wild-type ATXN1 enhances SCA1 pathogenesis, whereas increased levels of an evolutionarily conserved paralog of ATXN1, Ataxin 1-Like, ameliorate it. These data suggest that a partial loss of ATXN1 function contributes to SCA1. To address this possibility, we set out to determine if the SCA1 disease model (Atxn1154Q/+ mice) and the loss of Atxn1 function model (Atxn1−/− mice) share molecular changes that could potentially contribute to SCA1 pathogenesis. To identify transcriptional changes that might result from loss of function of ATXN1 in SCA1, we performed gene expression microarray studies on cerebellar RNA from Atxn1−/− and Atxn1154Q/+ cerebella and uncovered shared gene expression changes. We further show that mild overexpression of Ataxin-1-Like rescues several of the molecular and behavioral defects in Atxn1−/− mice. These results support a model in which Ataxin 1-Like overexpression represses SCA1 pathogenesis by compensating for a partial loss of function of Atxn1. Altogether, these data provide evidence that partial loss of Atxn1 function contributes to SCA1 pathogenesis and raise the possibility that loss-of-function mechanisms contribute to other dominantly inherited neurodegenerative diseases

Population Differences in Transcript-Regulator Expression Quantitative Trait Loci

Gene expression quantitative trait loci (eQTL) are useful for identifying single nucleotide polymorphisms (SNPs) associated with diseases. At times, a genetic variant may be associated with a master regulator involved in the manifestation of a disease. The downstream target genes of the master regulator are typically co-expressed and share biological function. Therefore, it is practical to screen for eQTLs by identifying SNPs associated with the targets of a transcript-regulator (TR). We used a multivariate regression with the gene expression of known targets of TRs and SNPs to identify TReQTLs in European (CEU) and African (YRI) HapMap populations. A nominal p-value of <1×10−6 revealed 234 SNPs in CEU and 154 in YRI as TReQTLs. These represent 36 independent (tag) SNPs in CEU and 39 in YRI affecting the downstream targets of 25 and 36 TRs respectively. At a false discovery rate (FDR) = 45%, one cis-acting tag SNP (within 1 kb of a gene) in each population was identified as a TReQTL. In CEU, the SNP (rs16858621) in Pcnxl2 was found to be associated with the genes regulated by CREM whereas in YRI, the SNP (rs16909324) was linked to the targets of miRNA hsa-miR-125a. To infer the pathways that regulate expression, we ranked TReQTLs by connectivity within the structure of biological process subtrees. One TReQTL SNP (rs3790904) in CEU maps to Lphn2 and is associated (nominal p-value = 8.1×10−7) with the targets of the X-linked breast cancer suppressor Foxp3. The structure of the biological process subtree and a gene interaction network of the TReQTL revealed that tumor necrosis factor, NF-kappaB and variants in G-protein coupled receptors signaling may play a central role as communicators in Foxp3 functional regulation. The potential pleiotropic effect of the Foxp3 TReQTLs was gleaned from integrating mRNA-Seq data and SNP-set enrichment into the analysis

The Protein Network Surrounding the Human Telomere Repeat Binding Factors TRF1, TRF2, and POT1

Telomere integrity (including telomere length and capping) is critical in overall genomic stability. Telomere repeat binding factors and their associated proteins play vital roles in telomere length regulation and end protection. In this study, we explore the protein network surrounding telomere repeat binding factors, TRF1, TRF2, and POT1 using dual-tag affinity purification in combination with multidimensional protein identification technology liquid chromatography - tandem mass spectrometry (MudPIT LC-MS/MS). After control subtraction and data filtering, we found that TRF2 and POT1 co-purified all six members of the telomere protein complex, while TRF1 identified five of six components at frequencies that lend evidence towards the currently accepted telomere architecture. Many of the known TRF1 or TRF2 interacting proteins were also identified. Moreover, putative associating partners identified for each of the three core components fell into functional categories such as DNA damage repair, ubiquitination, chromosome cohesion, chromatin modification/remodeling, DNA replication, cell cycle and transcription regulation, nucleotide metabolism, RNA processing, and nuclear transport. These putative protein-protein associations may participate in different biological processes at telomeres or, intriguingly, outside telomeres

Anemia prevalence in women of reproductive age in low- and middle-income countries between 2000 and 2018

Anemia is a globally widespread condition in women and is associated with reduced economic productivity and increased mortality worldwide. Here we map annual 2000–2018 geospatial estimates of anemia prevalence in women of reproductive age (15–49 years) across 82 low- and middle-income countries (LMICs), stratify anemia by severity and aggregate results to policy-relevant administrative and national levels. Additionally, we provide subnational disparity analyses to provide a comprehensive overview of anemia prevalence inequalities within these countries and predict progress toward the World Health Organization’s Global Nutrition Target (WHO GNT) to reduce anemia by half by 2030. Our results demonstrate widespread moderate improvements in overall anemia prevalence but identify only three LMICs with a high probability of achieving the WHO GNT by 2030 at a national scale, and no LMIC is expected to achieve the target in all their subnational administrative units. Our maps show where large within-country disparities occur, as well as areas likely to fall short of the WHO GNT, offering precision public health tools so that adequate resource allocation and subsequent interventions can be targeted to the most vulnerable populations