To study the association of antiphospholipid syndrome in patients with bad obstetric history

Background: Antiphospholipid syndrome is an autoimmune condition characterized by vascular thrombosis and /or pregnancy morbidity in the presence of antiphospholipid antibodies. A failure or significant delay in recognizing APS as the underlying disease entity may leave to the loss of an opportunity to prevent serious consequences of the disease and the associated pregnancy complications. Aim of the study was to study the association of Antiphospholipid Syndrome (APS) in patients with bad obstetric history (BOH).Methods: Patients registered in Obstetrics and Gynecology Department SAT Hospital, Medical College, Trivandrum, Kerala with bad obstetric history (BOH) meeting the inclusion and exclusion criteria were recruited for the study. They were followed up in the postnatal ward after abortion and preterm delivery as per protocol for bad obstetrics outcome evaluation. They were offered lab test in standard labs for APL Syndrome especially LAC and anti-cardiolipin antibodies IgM and IgG. Those tested positive were retested 12 weeks later also to confirm the test. Then the various adverse pregnancy outcomes were studied in both APLA positive and negative groups.Results: The association of APLA with bad obstetric history (BOH) in the present study are as follows- Late miscarriages-16%, miscarriages less than 10 weeks-12%, Preterm- 10.8%, unexplained death-14%, Severe Pre-eclampsia-12.3%, IUGR-11.8%, Abruption-11.1% of which late miscarriages more than10 weeks was the commonest association.Conclusions: The study shows that women with bad obstetric history (BOH) and those cases where miscarriage occurred after the appearance of foetal cardiac activity should be investigated for APLA in the preconceptional period itself in the next pregnancy earlier and if positive should be given prophylaxis for the same to prevent a miscarriage in future pregnancy

Outcome of large- and small-for-gestational-age babies born to mothers with pre-pregnancy and gestational diabetes mellitus versus without diabetes mellitus

Introduction: The prevalence of diabetes mellitus (DM) is on the increase among general population and prenatal mothers. The feto-maternal outcome of mothers with DM varies with the type of DM, pre-pregnancy or gestational (PPDM and GDM), and glycemic control. Objective: The objective of this study is to assess the outcome of small- and large-for gestational-age (SGA and LGA) babies born to a cohort of mothers with PPDM and GDM and without DM. Materials and Methods: This cohort study was conducted in a tertiary care teaching hospital. A total of 480 mothers and their newborn babies were enrolled before 6 weeks of gestation and were categorized into PPDM, GDM, and no DM subgroups. Mothers were managed as per the standard protocols. Parameters observed were optimum/suboptimum glycemic control, neonatal weight, GA, morbidity, mortality, and neonatal intensive care unit (NICU) stay. Results: A total of 19.5% mothers had PPDM, including 70 mothers already diagnosed as DM, while 39% had GDM and 41.5% had no DM. The detection rate of PPDM was 5.6% and GDM was 17.5%. Majority of the mothers with PPDM and GDM required insulin and two-third had optimum glycemic control. Good glycemic control resulted in more appropriate-for-GA babies. SGA babies were more in PPDM group (54%), followed by GDM (26%) and non-DM (21%) subgroups, while LGA babies were less in these groups, i.e., 9.6%, 5.9%, and 0.5%, respectively. The following observations were statistically significant among PPDM compared to GDM: SGA (relative risk [RR] 2.1, 95% confidence interval [CI] 2.9–3.6), congenital anomalies (RR 3.3, 95% CI 5.1–8.8), and neonatal mortality (RR 4, 95% CI 2.1–3.2). Prematurity and NICU admission with longer stay were also more in PPDM. Macrosomia and birth injury were more in GDM. Hypoglycemia, longer NICU stay, and macrosomia were more with poor glycemic control. Conclusions: A change in profile with more SGA and less LGA babies was noted in this study. Differential short-term outcomes were noted, based on the onset of DM and glycemic control. Pre-pregnancy/early first-trimester screen followed by second and third trimester screens and optimum glycemic control, throughout pregnancy, is recommended

Aberrant Promoter CpG Methylation Is a Mechanism for Impaired PHD3 Expression in a Diverse Set of Malignant Cells

The prolyl-hydroxylase domain family of enzymes (PHD1-3) plays an important role in the cellular response to hypoxia by negatively regulating HIF-α proteins. Disruption of this process can lead to up-regulation of factors that promote tumorigenesis. We observed decreased basal expression of PHD3 in prostate cancer tissue and tumor cell lines representing diverse tissues of origin. Furthermore, some cancer lines displayed a failure of PHD3 mRNA induction when introduced to a hypoxic environment. This study explores the mechanism by which malignancies neither basally express PHD3 nor induce PHD3 under hypoxic conditions.Using bisulfite sequencing and methylated DNA enrichment procedures, we identified human PHD3 promoter hypermethylation in prostate, breast, melanoma and renal carcinoma cell lines. In contrast, non-transformed human prostate and breast epithelial cell lines contained PHD3 CpG islands that were unmethylated and responded normally to hypoxia by upregulating PHD3 mRNA. Only treatment of cells lines containing PHD3 promoter hypermethylation with the demethylating drug 5-aza-2'-deoxycytidine significantly increased the expression of PHD3.We conclude that expression of PHD3 is silenced by aberrant CpG methylation of the PHD3 promoter in a subset of human carcinoma cell lines of diverse origin and that this aberrant cytosine methylation status is the mechanism by which these cancer cell lines fail to upregulate PHD3 mRNA. We further show that a loss of PHD3 expression does not correlate with an increase in HIF-1α protein levels or an increase in the transcriptional activity of HIF, suggesting that loss of PHD3 may convey a selective advantage in some cancers by affecting pathway(s) other than HIF

Bubbling and bistability in two parameter discrete systems

We present a graphical analysis of the mechanisms underlying the occurrences of bubbling sequences and bistability regions in the bifurcation scenario of a special class of one dimensional two parameter maps. The main result of the analysis is that whether it is bubbling or bistability is decided by the sign of the third derivative at the inflection point of the map function.Comment: LaTeX v2.09, 14 pages with 4 PNG figure

Soup to tree: the phylogeny of beetles inferred by mitochondrial metagenomics of a Bornean rainforest sample

In spite of the growth of molecular ecology, systematics and next-generation sequencing, the discovery and analysis of diversity is not currently integrated with building the tree-of-life. Tropical arthropod ecologists are well placed to accelerate this process if all specimens obtained via masstrapping, many of which will be new species, could be incorporated routinely in phylogeny reconstruction. Here we test a shotgun sequencing approach, whereby mitochondrial genomes are assembled from complex ecological mixtures via mitochondrial metagenomics, and demonstrate how the approach overcomes many of the taxonomic impediments to the study of biodiversity. DNA from ~500 beetle specimens, originating from a single rainforest canopy fogging sample from Borneo, was pooled and shotgun sequenced, followed by de novo assembly of complete and partial mitogenomes for 175 species. The phylogenetic tree obtained from this local sample was highly similar to that from existing mitogenomes selected for global coverage of major lineages of Coleoptera. When all sequences were combined, only minor topological changes are induced against this reference set, indicating an increasingly stable estimate of coleopteran phylogeny, whilst the ecological sample expands the tip-level representation of several lineages. Robust trees generated from ecological samples now enable an evolutionary framework for ecology. Meanwhile, the inclusion of uncharacterized samples in the tree-of-life rapidly expands taxon and biogeographic representation of lineages without morphological identification. Mitogenomes from shotgun sequencing of unsorted environmental samples and their associated metadata, placed robustly into the phylogenetic tree, constitute novel DNA ‘superbarcodes’ for testing hypotheses regarding global patterns of diversity

Bacterial Communities in Women with Bacterial Vaginosis: High Resolution Phylogenetic Analyses Reveal Relationships of Microbiota to Clinical Criteria

Bacterial vaginosis (BV) is a common condition that is associated with numerous adverse health outcomes and is characterized by poorly understood changes in the vaginal microbiota. We sought to describe the composition and diversity of the vaginal bacterial biota in women with BV using deep sequencing of the 16S rRNA gene coupled with species-level taxonomic identification. We investigated the associations between the presence of individual bacterial species and clinical diagnostic characteristics of BV.Broad-range 16S rRNA gene PCR and pyrosequencing were performed on vaginal swabs from 220 women with and without BV. BV was assessed by Amsel's clinical criteria and confirmed by Gram stain. Taxonomic classification was performed using phylogenetic placement tools that assigned 99% of query sequence reads to the species level. Women with BV had heterogeneous vaginal bacterial communities that were usually not dominated by a single taxon. In the absence of BV, vaginal bacterial communities were dominated by either Lactobacillus crispatus or Lactobacillus iners. Leptotrichia amnionii and Eggerthella sp. were the only two BV-associated bacteria (BVABs) significantly associated with each of the four Amsel's criteria. Co-occurrence analysis revealed the presence of several sub-groups of BVABs suggesting metabolic co-dependencies. Greater abundance of several BVABs was observed in Black women without BV.The human vaginal bacterial biota is heterogeneous and marked by greater species richness and diversity in women with BV; no species is universally present. Different bacterial species have different associations with the four clinical criteria, which may account for discrepancies often observed between Amsel and Nugent (Gram stain) diagnostic criteria. Several BVABs exhibited race-dependent prevalence when analyzed in separate groups by BV status which may contribute to increased incidence of BV in Black women. Tools developed in this project can be used to study microbial ecology in diverse settings at high resolution

The Liganding of Glycolipid Transfer Protein Is Controlled by Glycolipid Acyl Structure

Glycosphingolipids (GSLs) play major roles in cellular growth and development. Mammalian glycolipid transfer proteins (GLTPs) are potential regulators of cell processes mediated by GSLs and display a unique architecture among lipid binding/transfer proteins. The GLTP fold represents a novel membrane targeting/interaction domain among peripheral proteins. Here we report crystal structures of human GLTP bound to GSLs of diverse acyl chain length, unsaturation, and sugar composition. Structural comparisons show a highly conserved anchoring of galactosyl- and lactosyl-amide headgroups by the GLTP recognition center. By contrast, acyl chain chemical structure and occupancy of the hydrophobic tunnel dictate partitioning between sphingosine-in and newly-observed sphingosine-out ligand-binding modes. The structural insights, combined with computed interaction propensity distributions, suggest a concerted sequence of events mediated by GLTP conformational changes during GSL transfer to and/or from membranes, as well as during GSL presentation and/or transfer to other proteins

Family Planning Decisions, Perceptions and Gender Dynamics among Couples in Mwanza, Tanzania: A Qualitative Study.

Contraceptive use is low in developing countries which are still largely driven by male dominated culture and patriarchal values. This study explored family planning (FP) decisions, perceptions and gender dynamics among couples in Mwanza region of Tanzania. Twelve focus group discussions and six in-depth interviews were used to collect information from married or cohabiting males and females aged 18-49. The participants were purposively selected. Qualitative methods were used to explore family planning decisions, perceptions and gender dynamics among couples. A guide with questions related to family planning perceptions, decisions and gender dynamics was used. The discussions and interviews were tape-recorded, transcribed verbatim and analyzed manually and subjected to content analysis. Four themes emerged during the study. First, "risks and costs" which refer to the side effects of FP methods and the treatment of side -effects as well as the costs inherit in being labeled as an unfaithful spouse. Second, "male involvement" as men showed little interest in participating in family planning issues. However, the same men were mentioned as key decision-makers even on the number of children a couple should have and the child spacing of these children. Third, "gender relations and communication" as participants indicated that few women participated in decision-making on family planning and the number of children to have. Fourth, "urban-rural differences", life in rural favoring having more children than urban areas therefore, the value of children depended on the place of residence. Family Planning programs should adapt the promotion of communication as well as joint decision-making on FP among couples as a strategy aimed at enhancing FP use

MicroRNA 128a Increases Intracellular ROS Level by Targeting Bmi-1 and Inhibits Medulloblastoma Cancer Cell Growth by Promoting Senescence

BACKGROUND: MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate cell homeostasis by inhibiting translation or degrading mRNA of target genes, and thereby can act as tumor suppressor genes or oncogenes. The role of microRNAs in medulloblastoma has only recently been addressed. We hypothesized that microRNAs differentially expressed during normal CNS development might be abnormally regulated in medulloblastoma and are functionally important for medulloblastoma cell growth. METHODOLOGY AND PRINCIPAL FINDINGS: We examined the expression of microRNAs in medulloblastoma and then investigated the functional role of one specific one, miR-128a, in regulating medulloblastoma cell growth. We found that many microRNAs associated with normal neuronal differentiation are significantly down regulated in medulloblastoma. One of these, miR-128a, inhibits growth of medulloblastoma cells by targeting the Bmi-1 oncogene. In addition, miR-128a alters the intracellular redox state of the tumor cells and promotes cellular senescence. CONCLUSIONS AND SIGNIFICANCE: Here we report the novel regulation of reactive oxygen species (ROS) by microRNA 128a via the specific inhibition of the Bmi-1 oncogene. We demonstrate that miR-128a has growth suppressive activity in medulloblastoma and that this activity is partially mediated by targeting Bmi-1. This data has implications for the modulation of redox states in cancer stem cells, which are thought to be resistant to therapy due to their low ROS states