Characterization of MRP RNA-protein interactions within the perinucleolar compartment.

PubMed

Pollock, Callie; Daily, Kelly; Nguyen, Van Trung; Wang, Chen; Lewandowska, Marzena Anna; Bensaude, Olivier; Huang, Sui

2011-03-15

The perinucleolar compartment (PNC) forms in cancer cells and is highly enriched with a subset of polymerase III RNAs and RNA-binding proteins. Here we report that PNC components mitochondrial RNA-processing (MRP) RNA, pyrimidine tract-binding protein (PTB), and CUG-binding protein (CUGBP) interact in vivo, as demonstrated by coimmunoprecipitation and RNA pull-down experiments. Glycerol gradient analyses show that this complex is large and sediments at a different fraction from known MRP RNA-containing complexes, the MRP ribonucleoprotein ribozyme and human telomerase reverse transcriptase. Tethering PNC components to a LacO locus recruits other PNC components, further confirming the in vivo interactions. These interactions are present both in PNC-containing and -lacking cells. High-resolution localization analyses demonstrate that MRP RNA, CUGBP, and PTB colocalize at the PNC as a reticulated network, intertwining with newly synthesized RNA. Furthermore, green fluorescent protein (GFP)-PTB and GFP-CUGBP show a slower rate of fluorescence recovery after photobleaching at the PNC than in the nucleoplasm, illustrating the different molecular interaction of the complexes associated with the PNC. These findings support a working model in which the MRP RNA-protein complex becomes nucleated at the PNC in cancer cells and may play a role in gene expression regulation at the DNA locus that associates with the PNC.

Regulation of mRNA abundance by polypyrimidine tract-binding protein-controlled alternate 5' splice site choice.

PubMed

Hamid, Fursham M; Makeyev, Eugene V

2014-11-01

Alternative splicing (AS) provides a potent mechanism for increasing protein diversity and modulating gene expression levels. How alternate splice sites are selected by the splicing machinery and how AS is integrated into gene regulation networks remain important questions of eukaryotic biology. Here we report that polypyrimidine tract-binding protein 1 (Ptbp1/PTB/hnRNP-I) controls alternate 5' and 3' splice site (5'ss and 3'ss) usage in a large set of mammalian transcripts. A top scoring event identified by our analysis was the choice between competing upstream and downstream 5'ss (u5'ss and d5'ss) in the exon 18 of the Hps1 gene. Hps1 is essential for proper biogenesis of lysosome-related organelles and loss of its function leads to a disease called type 1 Hermansky-Pudlak Syndrome (HPS). We show that Ptbp1 promotes preferential utilization of the u5'ss giving rise to stable mRNAs encoding a full-length Hps1 protein, whereas bias towards d5'ss triggered by Ptbp1 down-regulation generates transcripts susceptible to nonsense-mediated decay (NMD). We further demonstrate that Ptbp1 binds to pyrimidine-rich sequences between the u5'ss and d5'ss and activates the former site rather than repressing the latter. Consistent with this mechanism, u5'ss is intrinsically weaker than d5'ss, with a similar tendency observed for other genes with Ptbp1-induced u5'ss bias. Interestingly, the brain-enriched Ptbp1 paralog Ptbp2/nPTB/brPTB stimulated the u5'ss utilization but with a considerably lower efficiency than Ptbp1. This may account for the tight correlation between Hps1 with Ptbp1 expression levels observed across mammalian tissues. More generally, these data expand our understanding of AS regulation and uncover a post-transcriptional strategy ensuring co-expression of a subordinate gene with its master regulator through an AS-NMD tracking mechanism.

The human insulin mRNA is partly translated via a cap- and eIF4A-independent mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fred, Rikard G., E-mail: Rikard.Fred@mcb.uu.se; Sandberg, Monica; Pelletier, Jerry

Highlights: {yields} The polypyrimidine tract binding protein binds to the 5'-UTR of the insulin mRNA. {yields} Insulin mRNA can be translated via a cap-independent mechanism. {yields} The fraction cap-independent insulin synthesis increases during conditions of stress. {yields} The {beta}-cell is able to uphold basal insulin biosynthesis under conditions of stress. -- Abstract: The aim of this study was to investigate whether cap-independent insulin mRNA translation occurs in human pancreatic islets at basal conditions, during stimulation at a high glucose concentration and at conditions of nitrosative stress. We also aimed at correlating cap-independent insulin mRNA translation with binding of the IRESmore » trans-acting factor polypyrimidine tract binding protein (PTB) to the 5'-UTR of insulin mRNA. For this purpose, human islets were incubated for 2 h in the presence of low (1.67 mM) or high glucose (16.7 mM). Nitrosative stress was induced by addition of 1 mM DETA/NO and cap-dependent mRNA translation was inhibited with hippuristanol. Insulin biosynthesis rates were determined by radioactive labeling and immunoprecipitation. PTB affinity to insulin mRNA 5'-UTR was assessed by a magnetic micro bead pull-down procedure. We observed that in the presence of 1.67 mM glucose, approximately 70% of the insulin mRNA translation was inhibited by hippuristanol. Corresponding value from islets incubated at 16.7 mM glucose was 93%. DETA/NO treatment significantly decreased the translation of insulin by 85% in high glucose incubated islets, and by 50% at a low glucose concentration. The lowered insulin biosynthesis rates of DETA/NO-exposed islets were further suppressed by hippuristanol with 55% at 16.7 mM glucose but not at 1.67 mM glucose. Thus, hippuristanol-induced inhibition of insulin biosynthesis was less pronounced in DETA/NO-treated islets as compared to control islets. We observed also that PTB bound specifically to the insulin mRNA 5'-UTR in vitro, and that this binding corresponded well with rates of cap-independent insulin biosynthesis at the different conditions. In conclusion, our studies show that insulin biosynthesis is mainly cap-dependent at a high glucose concentration, but that the cap-independent biosynthesis of insulin can constitute as much as 40-100% of all insulin biosynthesis during conditions of nitrosative stress. These data suggest that the pancreatic {beta}-cell is able to uphold basal insulin synthesis at conditions of starvation and stress via a cap- and eIF4A-independent mechanism, possibly mediated by the binding of PTB to the 5'-UTR of the human insulin mRNA.« less

Novel functions of CCM1 delimit the relationship of PTB/PH domains.

PubMed

Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

2017-10-01

Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and relationship of PTB, PH and FERM domains has been proposed, which extends the importance of the NPXY-PTB/PH interaction on the CSC signaling and/or other cell receptors with great potential pointing to new therapeutic strategies. The study provides new insight into the structural characteristics of PTB/PH domains, essential structural elements of PTB/PH domain required for NPXY motif-binding, and function and relationship among PTB, PH and FERM domains. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulation of mRNA Abundance by Polypyrimidine Tract-Binding Protein-Controlled Alternate 5′ Splice Site Choice

PubMed Central

Hamid, Fursham M.; Makeyev, Eugene V.

2014-01-01

Alternative splicing (AS) provides a potent mechanism for increasing protein diversity and modulating gene expression levels. How alternate splice sites are selected by the splicing machinery and how AS is integrated into gene regulation networks remain important questions of eukaryotic biology. Here we report that polypyrimidine tract-binding protein 1 (Ptbp1/PTB/hnRNP-I) controls alternate 5′ and 3′ splice site (5′ss and 3′ss) usage in a large set of mammalian transcripts. A top scoring event identified by our analysis was the choice between competing upstream and downstream 5′ss (u5′ss and d5′ss) in the exon 18 of the Hps1 gene. Hps1 is essential for proper biogenesis of lysosome-related organelles and loss of its function leads to a disease called type 1 Hermansky-Pudlak Syndrome (HPS). We show that Ptbp1 promotes preferential utilization of the u5′ss giving rise to stable mRNAs encoding a full-length Hps1 protein, whereas bias towards d5′ss triggered by Ptbp1 down-regulation generates transcripts susceptible to nonsense-mediated decay (NMD). We further demonstrate that Ptbp1 binds to pyrimidine-rich sequences between the u5′ss and d5′ss and activates the former site rather than repressing the latter. Consistent with this mechanism, u5′ss is intrinsically weaker than d5′ss, with a similar tendency observed for other genes with Ptbp1-induced u5′ss bias. Interestingly, the brain-enriched Ptbp1 paralog Ptbp2/nPTB/brPTB stimulated the u5′ss utilization but with a considerably lower efficiency than Ptbp1. This may account for the tight correlation between Hps1 with Ptbp1 expression levels observed across mammalian tissues. More generally, these data expand our understanding of AS regulation and uncover a post-transcriptional strategy ensuring co-expression of a subordinate gene with its master regulator through an AS-NMD tracking mechanism. PMID:25375251

INCOME INCONGRUITY, RACE AND PRETERM BIRTH (PTB)

EPA Science Inventory

Previous research using birth records has found income incongruity associated with adverse birth outcomes. The effects of negative income incongruity (reporting lower household income than the census tract median household income) on PTB (<37 weeks completed gestation) are examin...

Quaking and PTB control overlapping splicing regulatory networks during muscle cell differentiation

PubMed Central

Hall, Megan P.; Nagel, Roland J.; Fagg, W. Samuel; Shiue, Lily; Cline, Melissa S.; Perriman, Rhonda J.; Donohue, John Paul; Ares, Manuel

2013-01-01

Alternative splicing contributes to muscle development, but a complete set of muscle-splicing factors and their combinatorial interactions are unknown. Previous work identified ACUAA (“STAR” motif) as an enriched intron sequence near muscle-specific alternative exons such as Capzb exon 9. Mass spectrometry of myoblast proteins selected by the Capzb exon 9 intron via RNA affinity chromatography identifies Quaking (QK), a protein known to regulate mRNA function through ACUAA motifs in 3′ UTRs. We find that QK promotes inclusion of Capzb exon 9 in opposition to repression by polypyrimidine tract-binding protein (PTB). QK depletion alters inclusion of 406 cassette exons whose adjacent intron sequences are also enriched in ACUAA motifs. During differentiation of myoblasts to myotubes, QK levels increase two- to threefold, suggesting a mechanism for QK-responsive exon regulation. Combined analysis of the PTB- and QK-splicing regulatory networks during myogenesis suggests that 39% of regulated exons are under the control of one or both of these splicing factors. This work provides the first evidence that QK is a global regulator of splicing during muscle development in vertebrates and shows how overlapping splicing regulatory networks contribute to gene expression programs during differentiation. PMID:23525800

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.

PubMed

Feilen, Lukas P; Haubrich, Kevin; Strecker, Paul; Probst, Sabine; Eggert, Simone; Stier, Gunter; Sinning, Irmgard; Konietzko, Uwe; Kins, Stefan; Simon, Bernd; Wild, Klemens

2017-01-01

Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction

PubMed Central

Feilen, Lukas P.; Haubrich, Kevin; Strecker, Paul; Probst, Sabine; Eggert, Simone; Stier, Gunter; Sinning, Irmgard; Konietzko, Uwe; Kins, Stefan; Simon, Bernd; Wild, Klemens

2017-01-01

Physiological function and pathology of the Alzheimer’s disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling. PMID:28553201

Evidence for a role for the phosphotyrosine-binding domain of Shc in interleukin 2 signaling.

PubMed Central

Ravichandran, K S; Igras, V; Shoelson, S E; Fesik, S W; Burakoff, S J

1996-01-01

Stimulation via the T-cell growth factor interleukin 2 (IL-2) leads to tyrosine phosphorylation of Shc, the interaction of Shc with Grb2, and the Ras GTP/GDP exchange factor, mSOS. Shc also coprecipitates with the IL-2 receptor (IL-2R), and therefore, may link IL-2R to Ras activation. We have further characterized the Shc-IL-2R interaction and have made the following observations. (i) Among the two phosphotyrosine-interaction domains present in Shc, the phosphotyrosine-binding (PTB) domain, rather than its SH2 domain, interacts with the tyrosine-phosphorylated IL-2R beta chain. Moreover, the Shc-PTB domain binds a phosphopeptide derived from the IL-2R beta chain (corresponding to residues surrounding Y338, SCFTNQGpYFF) with high affinity. (ii) In vivo, mutant IL-2R beta chains lacking the acidic region of IL-2Rbeta (which contains Y338) fail to phosphorylate Shc. Furthermore, when wild type or mutant Shc proteins that lack the PTB domain were expressed in the IL-2-dependent CTLL-20 cell line, an intact Shc-PTB domain was required for Shc phosphorylation by the IL-2R, which provides further support for a Shc-PTB-IL-2R interaction in vivo. (iii) PTB and SH2 domains of Shc associate with different proteins in IL-2- and T-cell-receptor-stimulated lysates, suggesting that Shc, through the concurrent use of its two different phosphotyrosine-binding domains, could assemble multiple protein complexes. Taken together, our in vivo and in vitro observations suggest that the PTB domain of Shc interacts with Y338 of the IL-2R and provide evidence for a functional role for the Shc-PTB domain in IL-2 signaling. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8643566

IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured cells derived from FMDV-susceptible and -insusceptible animals.

PubMed

Kanda, Takehiro; Ozawa, Makoto; Tsukiyama-Kohara, Kyoko

2016-03-31

Foot-and-mouth disease virus (FMDV) possess a positive sense, single stranded RNA genome. Internal ribosomal entry site (IRES) element exists within its 5' untranslated region (5'UTR) of the viral RNA. Translation of the viral RNA is initiated by internal entry of the 40S ribosome within the IRES element. This process is facilitated by cellular factors known as IRES trans-acting factors (ITAFs). Foot-and-mouth disease (FMD) is host-restricted disease for cloven-hoofed animals such as cattle and pigs, but the factors determining the host range have not been identified yet. Although, ITAFs are known to promote IRES-mediated translation, these findings were confirmed only in cells derived from FMDV-insusceptible animals so far. We evaluated and compared the IRES-mediated translation activities among cell lines derived from four different animal species using bicistronic luciferase reporter plasmid, which possesses an FMDV-IRES element between Renilla and Firefly luciferase genes. Furthermore, we analyzed the effect of the cellular factors on IRES-mediated translation by silencing the cellular factors using siRNA in both FMDV-susceptible and -insusceptible animal cells. Our data indicated that IRES-mediated translational activity was not linked to FMDV host range. ITAF45 promoted IRES-mediated translation in all cell lines, and the effects of poly-pyrimidine tract binding protein (PTB) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) were observed only in FMDV-susceptible cells. Thus, PTB and 4E-BP1 may influence the host range of FMDV. IRES-mediated translation activity of FMDV was not predictive of its host range. ITAF45 promoted IRES-mediated translation in all cells, and the effects of PTB and 4E-BP1 were observed only in FMDV-susceptible cells.

Advances in the Prevention of Infection-Related Preterm Birth

PubMed Central

Lamont, Ronald F.

2015-01-01

Infection-related preterm birth (PTB) is more common at early gestational ages and is associated with major neonatal mortality and morbidity. Abnormal genital tract microflora in early pregnancy predicts late miscarriage and early PTB. Accordingly, it is logical to consider antibiotics as an intervention. Unfortunately, the conclusions of systematic reviews and meta-analyses (SR&MAs) carried out in an attempt to explain the confusion over the heterogeneity of individual studies are flawed by the fact that undue reliance was placed on studies which: (a) had a suboptimal choice of antibiotic (mainly metronidazole) or used antibiotics not recommended for the treatment of bacterial vaginosis (BV) or BV-related organisms; (b) used antibiotics too late in pregnancy to influence outcome (23–27 weeks); and (c) included women whose risk of PTB was not due to abnormal genital tract colonization and hence unlikely to respond to antibiotics. These risks included: (a) previous PTB of indeterminate etiology; (b) low weight/body mass index; or (c) detection of fetal fibronectin, ureaplasmas, Group B streptococcus or Trichomonas vaginalis). While individual studies have found benefit of antibiotic intervention for the prevention of PTB, in meta-analyses these effects have been negated by large methodologically flawed studies with negative results. As a result, many clinicians think that any antibiotic given at any time in pregnancy to any woman at risk of PTB will cause more harm than good. Recently, a more focused SR&MA has demonstrated that antibiotics active against BV-related organisms, used in women whose risk of PTB is due to abnormal microflora, and used early in pregnancy before irreversible inflammatory damage has occurred, can reduce the rate of PTB. This review presents those data, the background and attempts to explain the confusion using new information from culture-independent molecular-based techniques. It also gives guidance on the structure of putative future antibiotic intervention studies. PMID:26635788

HuB/C/D, nPTB, REST4, and miR-124 regulators of neuronal cell identity are also utilized in the lens.

PubMed

Bitel, Claudine L; Perrone-Bizzozero, Nora I; Frederikse, Peter H

2010-11-04

An interlocking network of transcription factors, RNA binding proteins, and miRNAs globally regulates gene expression and alternative splicing throughout development, and ensures the coordinated mutually exclusive expression of non-neural and neuronal forms of these factors during neurogenesis. Striking similarities between lens fiber cell and neuron cell morphology led us to determine if these factors are also used in the lens. HuR and polypyrimidine tract binding protein (PTB) have been described as 'global regulators' of RNA alternative splicing, stability, and translation in non-neuronal (including ectodermal) tissues examined to date in diverse species, and REST/NRSF (RE-1 Silencing Transcription Factor/Neuron Restrictive Silencing Factor) represses>2,000 neuronal genes in all non-neuronal tissues examined to date, but has not included the lens. During neurogenesis these factors are replaced by what has been considered neuron-specific HuB/C/D, nPTB, and alternatively spliced REST (REST4), which work with miR-124 to activate this battery of genes, comprehensively reprogram neuronal alternative splicing, and maintain their exclusive expression in post-mitotic neurons. Immunoprecipitation, western blot, immunofluorescence, and immunohistochemistry were used to determine the expression and distribution of proteins in mouse and rat lenses. Mobility shift assays were used to examine lenses for REST/NRSF DNA binding activity, and RT-PCR, DNA sequencing, and northern blots were used to identify RNA expression and alternative splicing events in lenses from mouse, rat, and goldfish (N. crassa). We demonstrated that REST, HuR, and PTB proteins are expressed predominantly in epithelial cells in mouse and rat lenses, and showed these factors are also replaced by the predominant expression of REST4, HuB/C/D and nPTB in post-mitotic fiber cells, together with miR-124 expression in vertebrate lenses. REST-regulated gene products were found to be restricted to fiber cells where REST is decreased. These findings predicted nPTB- and HuB/C/D-dependent splicing reactions can also occur in lenses, and we showed Neuronal C-src and Type 1 Neurofibromatosis 1 splicing as well as calcitonin gene related peptide (CGRP) and neural cell adhesion molecule (NCAM-180) alternative transcripts in lenses. Transgenic mice with increased HuD in lens also showed increased growth associated protein 43 (GAP43) and Ca++/Calmodulin dependent kinase IIα (CamKIIα) HuD target gene expression in the lens, similar to brain. The present study provides the first evidence this fundamental set of regulatory factors, previously considered to have a unique role in governing neurogenesis are also used in the lens, and raises questions about the origins of these developmental factors and mechanisms in lens and neuronal cells that also have a basic role in determining the neuronal phenotype.

HuB/C/D, nPTB, REST4, and miR-124 regulators of neuronal cell identity are also utilized in the lens

PubMed Central

Bitel, Claudine L.; Perrone-Bizzozero, Nora I.

2010-01-01

Purpose An interlocking network of transcription factors, RNA binding proteins, and miRNAs globally regulates gene expression and alternative splicing throughout development, and ensures the coordinated mutually exclusive expression of non-neural and neuronal forms of these factors during neurogenesis. Striking similarities between lens fiber cell and neuron cell morphology led us to determine if these factors are also used in the lens. HuR and polypyrimidine tract binding protein (PTB) have been described as ‘global regulators’ of RNA alternative splicing, stability, and translation in non-neuronal (including ectodermal) tissues examined to date in diverse species, and REST/NRSF (RE-1 Silencing Transcription Factor/Neuron Restrictive Silencing Factor) represses >2,000 neuronal genes in all non-neuronal tissues examined to date, but has not included the lens. During neurogenesis these factors are replaced by what has been considered neuron-specific HuB/C/D, nPTB, and alternatively spliced REST (REST4), which work with miR-124 to activate this battery of genes, comprehensively reprogram neuronal alternative splicing, and maintain their exclusive expression in post-mitotic neurons. Methods Immunoprecipitation, western blot, immunofluorescence, and immunohistochemistry were used to determine the expression and distribution of proteins in mouse and rat lenses. Mobility shift assays were used to examine lenses for REST/NRSF DNA binding activity, and RT–PCR, DNA sequencing, and northern blots were used to identify RNA expression and alternative splicing events in lenses from mouse, rat, and goldfish (N. crassa). Results We demonstrated that REST, HuR, and PTB proteins are expressed predominantly in epithelial cells in mouse and rat lenses, and showed these factors are also replaced by the predominant expression of REST4, HuB/C/D and nPTB in post-mitotic fiber cells, together with miR-124 expression in vertebrate lenses. REST-regulated gene products were found to be restricted to fiber cells where REST is decreased. These findings predicted nPTB- and HuB/C/D-dependent splicing reactions can also occur in lenses, and we showed Neuronal C-src and Type 1 Neurofibromatosis 1 splicing as well as calcitonin gene related peptide (CGRP) and neural cell adhesion molecule (NCAM-180) alternative transcripts in lenses. Transgenic mice with increased HuD in lens also showed increased growth associated protein 43 (GAP43) and Ca++/Calmodulin dependent kinase IIα (CamKIIα) HuD target gene expression in the lens, similar to brain. Conclusions The present study provides the first evidence this fundamental set of regulatory factors, previously considered to have a unique role in governing neurogenesis are also used in the lens, and raises questions about the origins of these developmental factors and mechanisms in lens and neuronal cells that also have a basic role in determining the neuronal phenotype. PMID:21139978

Drosophila Hephaestus/Polypyrimidine Tract Binding Protein Is Required for Dorso-Ventral Patterning and Regulation of Signalling between the Germline and Soma

PubMed Central

McDermott, Suzanne M.; Davis, Ilan

2013-01-01

In the Drosophila oocyte, gurken (grk) mRNA encodes a secreted TGF-α signal that specifies the future embryonic dorso-ventral axes by altering the fate of the surrounding epithelial follicle cells. We previously identified a number of RNA binding proteins that associate specifically with the 64 nucleotide grk localization signal, including the Drosophila orthologue of polypyrimidine tract-binding protein (PTB), Hephaestus (Heph). To test whether Heph is required for correct grk mRNA or protein function, we used immunoprecipitation to validate the association of Heph with grk mRNA and characterized the heph mutant phenotype. We found that Heph is a component of grk mRNP complexes but heph germline clones show that Heph is not required for grk mRNA localization. Instead, we identify a novel function for Heph in the germline and show that it is required for proper Grk protein localization. Furthermore, we show that Heph is required in the oocyte for the correct organization of the actin cytoskeleton and dorsal appendage morphogenesis. Our results highlight a requirement for an mRNA binding protein in the localization of Grk protein, which is independent of mRNA localization, and we propose that Heph is required in the germline for efficient Grk signalling to the somatic follicle cells during dorso-ventral patterning. PMID:23894566

INCORPORATION OF LABELED NITRIC OXIDE INTO RESPIRATORY TRACT LINING FLUIDS AND BLOOD PLASMA DURING LUNG INFLAMMATION

EPA Science Inventory

Incorporation of labeled nitric oxide (N18O) into respiratory tract lining fluids and blood plasma during lung inflammation. Slade, R., Norwood, J., Crissman, K., McKee, J., Hatch, G. PTB, ETD, NHEERL, ORD, USEPA, Res. Tri. Pk., NC

Our earlier studies have demonstrated t...

TDP-43 functions within a network of hnRNP proteins to inhibit the production of a truncated human SORT1 receptor.

PubMed

Mohagheghi, Fatemeh; Prudencio, Mercedes; Stuani, Cristiana; Cook, Casey; Jansen-West, Karen; Dickson, Dennis W; Petrucelli, Leonard; Buratti, Emanuele

2016-02-01

The aggregation and mislocalization of RNA-binding proteins leads to the aberrant regulation of RNA metabolism and is a key feature of many neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia. However, the pathological consequences of abnormal deposition of TDP-43 and other RNA-binding proteins remain unclear, as the specific molecular events that drive neurodegeneration have been difficult to identify and continue to be elusive. Here, we provide novel insight into the complexity of the RNA-binding protein network by demonstrating that the inclusion of exon 17b in the SORT1 mRNA, a pathologically relevant splicing event known to be regulated by TDP-43, is also considerably affected by additional RNA-binding proteins, such as hnRNP L, PTB/nPTB and hnRNP A1/A2. Most importantly, the expression of hnRNP A1/A2 and PTB/nPTB is significantly altered in patients with frontotemporal dementia with TDP-43-positive inclusions (FTLD-TDP), indicating that perturbations in RNA metabolism and processing in FTLD-TDP are not exclusively driven by a loss of TDP-43 function. These results also suggest that a comprehensive assessment of the RNA-binding protein network will dramatically advance our current understanding of the role of TDP-43 in disease pathogenesis, as well as enhance both diagnostic and therapeutic capabilities. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Structural insights into FRS2α PTB domain recognition by neurotrophin receptor TrkB.

PubMed

Zeng, Lei; Kuti, Miklos; Mujtaba, Shiraz; Zhou, Ming-Ming

2014-07-01

The fibroblast growth factor receptor (FGFR) substrate 2 (FRS2) family proteins function as scaffolding adapters for receptor tyrosine kinases (RTKs). The FRS2α proteins interact with RTKs through the phosphotyrosine-binding (PTB) domain and transfer signals from the activated receptors to downstream effector proteins. Here, we report the nuclear magnetic resonance structure of the FRS2α PTB domain bound to phosphorylated TrkB. The structure reveals that the FRS2α-PTB domain is comprised of two distinct but adjacent pockets for its mutually exclusive interaction with either nonphosphorylated juxtamembrane region of the FGFR, or tyrosine phosphorylated peptides TrkA and TrkB. The new structural insights suggest rational design of selective small molecules through targeting of the two conjunct pockets in the FRS2α PTB domain. © 2014 Wiley Periodicals, Inc.

INCOME INCONGRUITY, RACE AND PRETERM BIRTH

EPA Science Inventory

Previous research with vital records finds income incongruity associated with adverse birth outcomes. We examined the effects of negative income incongruity (reporting lower household income than the census tract median household income) on preterm birth (PTB <37 weeks completed ...

Fetal gender differences in preterm birth: findings in a North American cohort.

PubMed

McGregor, J A; Leff, M; Orleans, M; Baron, A

1992-01-01

A higher incidence of preterm birth (PTB) and premature rupture of membranes (PROM) has been observed among women delivering male newborns compared with female newborns in different populations. Some authors have speculated that this higher incidence of PTB may be related to the relatively greater weight at lower gestational age of male newborns compared with female newborns. Others have suggested that the greater incidence of PTB and PROM is caused by an increased vulnerability to infection in women carrying males. To understand possible pathogenic factors leading to PTB further, we examined the association between PTB and infant gender in a cohort of North American women. In addition, incidences of PROM, chorioamnionitis, and postpartum endometritis were analyzed for women delivering males versus females. Overall, males were more likely than females to deliver at 33 to 36 weeks' gestation (OR = 1.21; 95% CI: 1.02-1.42). This increase in PTB among males was not accompanied by an increased number of males with low birthweight; rather, males were less likely than females to weigh between 2000 and 2499 gm (OR = 0.71; 95% CI: 0.60-0.84). The difference in PTB by gender could not be explained by an increased occurrence of PROM, chorioamnionitis, endometritis, or other infection-linked processes. Our findings suggest that shorter gestation in males in this population may be related to their relatively increased size and birthweight. Male gender-associated factors that predispose to infection-mediated preterm birth may play greater roles in populations at higher risk for reproductive tract infection during pregnancy.

Beyond the Cross-Sectional: Neighborhood Poverty Histories and Preterm Birth

PubMed Central

Margerison-Zilko, Claire; Jun, Jina; Marchi, Kristen; Fingar, Kathryn; Braveman, Paula

2015-01-01

Objectives. We examined associations between longitudinal neighborhood poverty trajectories and preterm birth (PTB). Methods. Using data from the Neighborhood Change Database (1970–2000) and the American Community Survey (2005–2009), we categorized longitudinal trajectories of poverty for California neighborhoods (i.e., census tracts). Birth data included 23 291 singleton California births from the Maternal and Infant Health Assessment (2003–2009). We estimated associations (adjusted for individual-level covariates) between PTB and longitudinal poverty trajectories and compared these to associations using traditional, cross-sectional measures of poverty. Results. Compared to neighborhoods with long-term low poverty, those with long-term high poverty and those that experienced increasing poverty early in the study period had 41% and 37% increased odds of PTB (95% confidence interval [CI] = 1.18, 1.69 and 1.09, 1.72, respectively). High (compared with low) cross-sectional neighborhood poverty was not associated with PTB (odds ratio = 1.08; 95% CI = 0.91, 1.28). Conclusions. Neighborhood poverty histories may contribute to an understanding of perinatal health and should be considered in future research. PMID:25880941

Beyond the cross-sectional: neighborhood poverty histories and preterm birth.

PubMed

Margerison-Zilko, Claire; Cubbin, Catherine; Jun, Jina; Marchi, Kristen; Fingar, Kathryn; Braveman, Paula

2015-06-01

We examined associations between longitudinal neighborhood poverty trajectories and preterm birth (PTB). Using data from the Neighborhood Change Database (1970-2000) and the American Community Survey (2005-2009), we categorized longitudinal trajectories of poverty for California neighborhoods (i.e., census tracts). Birth data included 23 291 singleton California births from the Maternal and Infant Health Assessment (2003-2009). We estimated associations (adjusted for individual-level covariates) between PTB and longitudinal poverty trajectories and compared these to associations using traditional, cross-sectional measures of poverty. Compared to neighborhoods with long-term low poverty, those with long-term high poverty and those that experienced increasing poverty early in the study period had 41% and 37% increased odds of PTB (95% confidence interval [CI] = 1.18, 1.69 and 1.09, 1.72, respectively). High (compared with low) cross-sectional neighborhood poverty was not associated with PTB (odds ratio = 1.08; 95% CI = 0.91, 1.28). Neighborhood poverty histories may contribute to an understanding of perinatal health and should be considered in future research.

Does neighborhood deprivation modify the effect of preterm birth on children's first grade academic performance?

PubMed

Richards, Jennifer L; Chapple-McGruder, Theresa; Williams, Bryan L; Kramer, Michael R

2015-05-01

Children's cognitive development and academic performance are linked to both fetal and early childhood factors, including preterm birth and family socioeconomic status. We evaluated whether the relationship between preterm birth (PTB) and first grade standardized test performance among Georgia public school students was modified by neighborhood deprivation in early childhood. The Georgia Birth to School cohort followed 327,698 children born in Georgia from 1998 to 2002 through to end-of-year first grade standardized tests. Binomial and log-binomial generalized estimating equations were used to estimate risk differences and risk ratios for the associations of both PTB and the Neighborhood Deprivation Index for the census tract in which each child's mother resided at the time of birth with test failure (versus passing). The presence of additive and multiplicative interaction was assessed. PTB was strongly associated with test failure, with increasing risk for earlier gestational ages. There was positive additive interaction between PTB and neighborhood deprivation. The main effect of PTB versus term birth increased risk of mathematics failure: 15.9% (95%CI: 13.3-18.5%) for early, 5.0% (95% CI: 4.1-5.9%) for moderate, and 1.3% (95%CI: 0.9-1.7%) for late preterm. Each 1 standard deviation increase in neighborhood deprivation was associated with 0.6% increased risk of mathematics failure. For children exposed to both PTB and higher neighborhood deprivation, test failure was 4.8%, 1.5%, and 0.8% greater than the sum of two main effects for early, moderate, and late PTB, respectively. Results were similar, but slightly attenuated, for reading and English/language arts. Our results suggest that PTB and neighborhood deprivation additively interact to produce greater risk among doubly exposed children than would be predicted from the sum of the effects of the two exposures. Understanding socioeconomic disparities in the effect of PTB on academic outcomes at school entry is important for targeting of early childhood interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Maternal Serological Response to Intrauterine Ureaplasma sp. Infection and Prediction of Risk of Pre-Term Birth

PubMed Central

Ireland, Demelza J.; Keelan, Jeffrey A.

2014-01-01

Pre-term birth (PTB) associated with intrauterine infection and inflammation (IUI) is the major cause of early PTB less than 32 weeks of gestation. Ureaplasma spp. are common commensals of the urogenital tract in pregnancy and are the most commonly identified microorganisms in amniotic fluid of pre-term pregnancies. While we have an understanding of the causal relationship between intra-amniotic infection, inflammation and PTB, we are still unable to explain why vaginal Ureaplasma sp. colonization is tolerated in some women but causes PTB in others. It is now known that placental tissues are frequently colonized by bacteria even in apparently healthy pregnancies delivered at term; usually this occurs in the absence of a significant local inflammatory response. It appears, therefore, that the site, nature, and magnitude of the immune response to infiltrating microorganisms are key in determining pregnancy outcome. Some evidence exists that the maternal serological response to Ureaplasma sp. colonization may be predictive of adverse pregnancy outcome, although issues such as the importance of virulence factors (serovars) and the timing, magnitude, and functional consequences of the immune response await clarification. This mini-review discusses the evidence linking the maternal immune response to risk of PTB and the potential applications of maternal serological analysis for predicting obstetric outcome. PMID:25538708

A deep learning framework for modeling structural features of RNA-binding protein targets

PubMed Central

Zhang, Sai; Zhou, Jingtian; Hu, Hailin; Gong, Haipeng; Chen, Ligong; Cheng, Chao; Zeng, Jianyang

2016-01-01

RNA-binding proteins (RBPs) play important roles in the post-transcriptional control of RNAs. Identifying RBP binding sites and characterizing RBP binding preferences are key steps toward understanding the basic mechanisms of the post-transcriptional gene regulation. Though numerous computational methods have been developed for modeling RBP binding preferences, discovering a complete structural representation of the RBP targets by integrating their available structural features in all three dimensions is still a challenging task. In this paper, we develop a general and flexible deep learning framework for modeling structural binding preferences and predicting binding sites of RBPs, which takes (predicted) RNA tertiary structural information into account for the first time. Our framework constructs a unified representation that characterizes the structural specificities of RBP targets in all three dimensions, which can be further used to predict novel candidate binding sites and discover potential binding motifs. Through testing on the real CLIP-seq datasets, we have demonstrated that our deep learning framework can automatically extract effective hidden structural features from the encoded raw sequence and structural profiles, and predict accurate RBP binding sites. In addition, we have conducted the first study to show that integrating the additional RNA tertiary structural features can improve the model performance in predicting RBP binding sites, especially for the polypyrimidine tract-binding protein (PTB), which also provides a new evidence to support the view that RBPs may own specific tertiary structural binding preferences. In particular, the tests on the internal ribosome entry site (IRES) segments yield satisfiable results with experimental support from the literature and further demonstrate the necessity of incorporating RNA tertiary structural information into the prediction model. The source code of our approach can be found in https://github.com/thucombio/deepnet-rbp. PMID:26467480

Characterization of MRP RNA–protein interactions within the perinucleolar compartment

PubMed Central

Pollock, Callie; Daily, Kelly; Nguyen, Van Trung; Wang, Chen; Lewandowska, Marzena Anna; Bensaude, Olivier; Huang, Sui

2011-01-01

The perinucleolar compartment (PNC) forms in cancer cells and is highly enriched with a subset of polymerase III RNAs and RNA-binding proteins. Here we report that PNC components mitochondrial RNA–processing (MRP) RNA, pyrimidine tract–binding protein (PTB), and CUG-binding protein (CUGBP) interact in vivo, as demonstrated by coimmunoprecipitation and RNA pull-down experiments. Glycerol gradient analyses show that this complex is large and sediments at a different fraction from known MRP RNA–containing complexes, the MRP ribonucleoprotein ribozyme and human telomerase reverse transcriptase. Tethering PNC components to a LacO locus recruits other PNC components, further confirming the in vivo interactions. These interactions are present both in PNC-containing and -lacking cells. High-resolution localization analyses demonstrate that MRP RNA, CUGBP, and PTB colocalize at the PNC as a reticulated network, intertwining with newly synthesized RNA. Furthermore, green fluorescent protein (GFP)–PTB and GFP-CUGBP show a slower rate of fluorescence recovery after photobleaching at the PNC than in the nucleoplasm, illustrating the different molecular interaction of the complexes associated with the PNC. These findings support a working model in which the MRP RNA–protein complex becomes nucleated at the PNC in cancer cells and may play a role in gene expression regulation at the DNA locus that associates with the PNC. PMID:21233287

Disabled is a putative adaptor protein that functions during signaling by the sevenless receptor tyrosine kinase.

PubMed

Le, N; Simon, M A

1998-08-01

DRK, the Drosophila homolog of the SH2-SH3 domain adaptor protein Grb2, is required during signaling by the sevenless receptor tyrosine kinase (SEV). One role of DRK is to provide a link between activated SEV and the Ras1 activator SOS. We have investigated the possibility that DRK performs other functions by identifying additional DRK-binding proteins. We show that the phosphotyrosine-binding (PTB) domain-containing protein Disabled (DAB) binds to the DRK SH3 domains. DAB is expressed in the ommatidial clusters, and loss of DAB function disrupts ommatidial development. Moreover, reduction of DAB function attenuates signaling by a constitutively activated SEV. Our biochemical analysis suggests that DAB binds SEV directly via its PTB domain, becomes tyrosine phosphorylated upon SEV activation, and then serves as an adaptor protein for SH2 domain-containing proteins. Taken together, these results indicate that DAB is a novel component of the SEV signaling pathway.

The Cytoplasmic Adaptor Protein Dok7 Activates the Receptor Tyrosine Kinase MuSK via Dimerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergamin, E.; Hallock, P; Burden, S

Formation of the vertebrate neuromuscular junction requires, among others proteins, Agrin, a neuronally derived ligand, and the following muscle proteins: LRP4, the receptor for Agrin; MuSK, a receptor tyrosine kinase (RTK); and Dok7 (or Dok-7), a cytoplasmic adaptor protein. Dok7 comprises a pleckstrin-homology (PH) domain, a phosphotyrosine-binding (PTB) domain, and C-terminal sites of tyrosine phosphorylation. Unique among adaptor proteins recruited to RTKs, Dok7 is not only a substrate of MuSK, but also an activator of MuSK's kinase activity. Here, we present the crystal structure of the Dok7 PH-PTB domains in complex with a phosphopeptide representing the Dok7-binding site on MuSK.more » The structure and biochemical data reveal a dimeric arrangement of Dok7 PH-PTB that facilitates trans-autophosphorylation of the kinase activation loop. The structure provides the molecular basis for MuSK activation by Dok7 and for rationalizing several Dok7 loss-of-function mutations found in patients with congenital myasthenic syndromes.« less

The human insulin receptor mRNA contains a functional internal ribosome entry segment

PubMed Central

Spriggs, Keith A.; Cobbold, Laura C.; Ridley, Simon H.; Coldwell, Mark; Bottley, Andrew; Bushell, Martin; Willis, Anne E.; Siddle, Kenneth

2009-01-01

Regulation of mRNA translation is an important mechanism determining the level of expression of proteins in eukaryotic cells. Translation is most commonly initiated by cap-dependent scanning, but many eukaryotic mRNAs contain internal ribosome entry segments (IRESs), providing an alternative means of initiation capable of independent regulation. Here, we show by using dicistronic luciferase reporter vectors that the 5′-UTR of the mRNA encoding human insulin receptor (hIR) contains a functional IRES. RNAi-mediated knockdown showed that the protein PTB was required for maximum IRES activity. Electrophoretic mobility shift assays confirmed that PTB1, PTB2 and nPTB, but not unr or PTB4, bound to hIR mRNA, and deletion mapping implicated a CCU motif 448 nt upstream of the initiator AUG in PTB binding. The IR-IRES was functional in a number of cell lines, and most active in cells of neuronal origin, as assessed by luciferase reporter assays. The IRES was more active in confluent than sub-confluent cells, but activity did not change during differentiation of 3T3-L1 fibroblasts to adipocytes. IRES activity was stimulated by insulin in sub-confluent cells. The IRES may function to maintain expression of IR protein in tissues such as the brain where mRNA translation by cap-dependent scanning is less effective. PMID:19654240

Methylenetetrahydrofolate reductase polymorphisms at 3'-untranslated region are associated with susceptibility to preterm birth.

PubMed

Zhu, Qin; Chen, Ying; Dai, Jianrong; Wang, Benjing; Liu, Minjuan; Wang, Yun; Tao, Jianying; Li, Hong

2015-01-01

Etiology and mechanism of preterm birth (PTB) is complicated. Genetic susceptibility is one of the key factors involved in the pathogenic mechanism underlying PTB. A subset of single nucleotide polymorphisms (SNPs) selected by bioinformatics approach from 3'-untranslated region (3'-UTR) of methylenetetrahydrofolate reductase (MTHFR) gene were subjected to SNaPshot analysis in a case-control study. Three SNPs (rs45451599, rs1537515, rs1537516) were simultaneously tested in one tube, among 1,135 DNA samples including 480 PTBs and 655 term controls. Two perfectly correlated (r(2)=1) SNPs, rs1537515 and rs1537516, were found significantly associated with PTB susceptibility [P=0.012; OR: 0.65; 95% confidence interval (CI), 0.47-0.91]. The frequencies of the minor alleles were lower in PTB cases than in controls, which the frequencies were 0.066 in PTB cases and 0.095 in controls. G and T allele frequencies of rs1537515 were the same with rs1537516 (P=0.011; OR: 0.666; 95% CI, 0.49-0.91). Rs45451599 was not found associated with PTB (P=0.52; OR: 0.76; 95% CI, 0.33-1.74). The 18-25 nucleotides in length of microRNAs (miRNAs) which can regulate gene expressions are involved in binding partial complementary sequences within 3'-UTR. The two loci are at 3'-UTR of MTHFR mRNA. Rs1537516 is a potential target of miR-1304-3p, while rs1537515 is miR-1224-3p and miR-3150-5p. In conclusion, rs1537515 and rs1537516 within the 3'-UTR of the MTHFR gene may be associated with susceptibility to PTB.

Age-Dependent Association between Pulmonary Tuberculosis and Common TOX Variants in the 8q12–13 Linkage Region

PubMed Central

Grant, Audrey V.; El Baghdadi, Jamila; Sabri, Ayoub; El Azbaoui, Safa; Alaoui-Tahiri, Kebir; Abderrahmani Rhorfi, Ismail; Gharbaoui, Yasser; Abid, Ahmed; Benkirane, Majid; Raharimanga, Vaomalala; Richard, Vincent; Orlova, Marianna; Boland, Anne; Migaud, Mélanie; Okada, Satoshi; Nolan, Daniel K.; Bustamante, Jacinta; Barreiro, Luis B.; Schurr, Erwin; Boisson-Dupuis, Stephanie; Rasolofo, Voahangy; Casanova, Jean-Laurent; Abel, Laurent

2013-01-01

Only a small fraction of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB) in their lifetime. Genetic epidemiological evidence suggests a genetic determinism of pulmonary TB (PTB), but the molecular basis of genetic predisposition to PTB remains largely unknown. We used a positional-cloning approach to carry out ultrafine linkage-disequilibrium mapping of a previously identified susceptibility locus in chromosomal region 8q12–13 by genotyping 3,216 SNPs in a family-based Moroccan sample including 286 offspring with PTB. We observed 44 PTB-associated SNPs (p < 0.01), which were genotyped in an independent set of 317 cases and 650 controls from Morocco. A single signal, consisting of two correlated SNPs close to TOX, rs1568952 and rs2726600 (combined p = 1.1 × 10−5 and 9.2 × 10−5, respectively), was replicated. Stronger evidence of association was found in individuals who developed PTB before the age of 25 years (combined p for rs1568952 = 4.4 × 10−8; odds ratio of PTB for AA versus AG/GG = 3.09 [1.99–4.78]). The association with rs2726600 (p = 0.04) was subsequently replicated in PTB-affected subjects under 25 years in a study of 243 nuclear families from Madagascar. Stronger evidence of replication in Madagascar was obtained for additional SNPs in strong linkage disequilibrium with the two initial SNPs (p = 0.003 for rs2726597), further confirming the signal. We thus identified around rs1568952 and rs2726600 a cluster of SNPs strongly associated with early-onset PTB in Morocco and Madagascar. SNP rs2726600 is located in a transcription-factor binding site in the 3′ region of TOX, and further functional explorations will focus on CD4 T lymphocytes. PMID:23415668

Phosphotyrosine signaling proteins that drive oncogenesis tend to be highly interconnected.

PubMed

Koytiger, Grigoriy; Kaushansky, Alexis; Gordus, Andrew; Rush, John; Sorger, Peter K; MacBeath, Gavin

2013-05-01

Mutation and overexpression of receptor tyrosine kinases or the proteins they regulate serve as oncogenic drivers in diverse cancers. To better understand receptor tyrosine kinase signaling and its link to oncogenesis, we used protein microarrays to systematically and quantitatively measure interactions between virtually every SH2 or PTB domain encoded in the human genome and all known sites of tyrosine phosphorylation on 40 receptor tyrosine kinases and on most of the SH2 and PTB domain-containing adaptor proteins. We found that adaptor proteins, like RTKs, have many high affinity bindings sites for other adaptor proteins. In addition, proteins that drive cancer, including both receptors and adaptor proteins, tend to be much more highly interconnected via networks of SH2 and PTB domain-mediated interactions than nononcogenic proteins. Our results suggest that network topological properties such as connectivity can be used to prioritize new drug targets in this well-studied family of signaling proteins.

Molecular Mechanisms of SH2- and PTB-Domain-Containing Proteins in Receptor Tyrosine Kinase Signaling

PubMed Central

Wagner, Melany J.; Stacey, Melissa M.; Liu, Bernard A.; Pawson, Tony

2013-01-01

Intracellular signaling is mediated by reversible posttranslational modifications (PTMs) that include phosphorylation, ubiquitination, and acetylation, among others. In response to extracellular stimuli such as growth factors, receptor tyrosine kinases (RTKs) typically dimerize and initiate signaling through phosphorylation of their cytoplasmic tails and downstream scaffolds. Signaling effectors are recruited to these phosphotyrosine (pTyr) sites primarily through Src homology 2 (SH2) domains and pTyr-binding (PTB) domains. This review describes how these conserved domains specifically recognize pTyr residues and play a major role in mediating precise downstream signaling events. PMID:24296166

Molecular mechanisms of SH2- and PTB-domain-containing proteins in receptor tyrosine kinase signaling.

PubMed

Wagner, Melany J; Stacey, Melissa M; Liu, Bernard A; Pawson, Tony

2013-12-01

Intracellular signaling is mediated by reversible posttranslational modifications (PTMs) that include phosphorylation, ubiquitination, and acetylation, among others. In response to extracellular stimuli such as growth factors, receptor tyrosine kinases (RTKs) typically dimerize and initiate signaling through phosphorylation of their cytoplasmic tails and downstream scaffolds. Signaling effectors are recruited to these phosphotyrosine (pTyr) sites primarily through Src homology 2 (SH2) domains and pTyr-binding (PTB) domains. This review describes how these conserved domains specifically recognize pTyr residues and play a major role in mediating precise downstream signaling events.

A Novel Function of the Fe65 Neuronal Adaptor in Estrogen Receptor Action in Breast Cancer Cells*

PubMed Central

Sun, Yuefeng; Kasiappan, Ravi; Tang, Jinfu; Webb, Panida L.; Quarni, Waise; Zhang, Xiaohong; Bai, Wenlong

2014-01-01

Fe65 is a multidomain adaptor with established functions in neuronal cells and neurodegeneration diseases. It binds to the C terminus of the Aβ amyloid precursor protein and is involved in regulating gene transcription. The present studies show that Fe65 is expressed in breast cancer (BCa) cells and acts as an ERα transcriptional coregulator that is recruited by 17β-estradiol to the promoters of estrogen target genes. Deletion analyses mapped the ERα binding domain to the phosphotyrosine binding domain 2 (PTB2). Ectopic Fe65 increased the transcriptional activity of the ERα in a PTB2-dependent manner in reporter assays. Fe65 knockdown decreased, whereas its stable expression increased the transcriptional activity of endogenous ERα in BCa cells and the ability of estrogens to stimulate target gene expression, ERα, and coactivator recruitment to target gene promoters and cell growth. Furthermore, Fe65 expression decreased the antagonistic activity of tamoxifen (TAM), suggesting a role for Fe65 in TAM resistance. Overall, the studies define a novel role for the neuronal adaptor in estrogen actions in BCa cells. PMID:24619425

Numb endocytic adapter proteins regulate the transport and processing of the amyloid precursor protein in an isoform-dependent manner: implications for Alzheimer disease pathogenesis.

PubMed

Kyriazis, George A; Wei, Zelan; Vandermey, Miriam; Jo, Dong-Gyu; Xin, Ouyang; Mattson, Mark P; Chan, Sic L

2008-09-12

Central to the pathogenesis of Alzheimer disease is the aberrant processing of the amyloid precursor protein (APP) to generate amyloid beta-peptide (Abeta), the principle component of amyloid plaques. The cell fate determinant Numb is a phosphotyrosine binding domain (PTB)-containing endocytic adapter protein that interacts with the carboxyl-terminal domain of APP. The physiological relevance of this interaction is unknown. Mammals produce four alternatively spliced variants of Numb that differ in the length of their PTB and proline-rich region. In the current study, we determined the influence of the four human Numb isoforms on the intracellular trafficking and processing of APP. Stable expression of Numb isoforms that differ in the PTB but not in the proline-rich region results in marked differences in the sorting of APP to the recycling and degradative pathways. Neural cells expressing Numb isoforms that lack the insert in the PTB (short PTB (SPTB)) exhibited marked accumulation of APP in Rab5A-labeled early endosomal and recycling compartments, whereas those expressing isoforms with the insertion in the PTB (long PTB (LPTB)) exhibited reduced amounts of cellular APP and its proteolytic derivatives relative to parental control cells. Neither the activities of the beta- and gamma-secretases nor the expression of APP mRNA were significantly different in the stably transfected cells, suggesting that the differential effects of the Numb proteins on APP metabolism is likely to be secondary to altered APP trafficking. In addition, the expression of SPTB-Numb increases at the expense of LPTB-Numb in neuronal cultures subjected to stress, suggesting a role for Numb in stress-induced Abeta production. Taken together, these results suggest distinct roles for the human Numb isoforms in APP metabolism and may provide a novel potential link between altered Numb isoform expression and increased Abeta generation.

PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2.

PubMed

Zheng, Sika; Gray, Erin E; Chawla, Geetanjali; Porse, Bo Torben; O'Dell, Thomas J; Black, Douglas L

2012-01-15

Postsynaptic density protein 95 (PSD-95) is essential for synaptic maturation and plasticity. Although its synaptic regulation has been widely studied, the control of PSD-95 cellular expression is not understood. We found that Psd-95 was controlled post-transcriptionally during neural development. Psd-95 was transcribed early in mouse embryonic brain, but most of its product transcripts were degraded. The polypyrimidine tract binding proteins PTBP1 and PTBP2 repressed Psd-95 (also known as Dlg4) exon 18 splicing, leading to premature translation termination and nonsense-mediated mRNA decay. The loss of first PTBP1 and then of PTBP2 during embryonic development allowed splicing of exon 18 and expression of PSD-95 late in neuronal maturation. Re-expression of PTBP1 or PTBP2 in differentiated neurons inhibited PSD-95 expression and impaired the development of glutamatergic synapses. Thus, expression of PSD-95 during early neural development is controlled at the RNA level by two PTB proteins whose sequential downregulation is necessary for synapse maturation.

Cocrystal structure of the ICAP1 PTB domain in complex with a KRIT1 peptide

PubMed Central

Liu, Weizhi; Boggon, Titus J.

2013-01-01

Integrin cytoplasmic domain-associated protein-1 (ICAP1) is a suppressor of integrin activation and directly binds to the cytoplasmic tail of β1 integrins; its binding suppresses integrin activation by competition with talin. Krev/Rap1 interaction trapped-1 (KRIT1) releases ICAP1 suppression of integrin activation by sequestering ICAP1 away from integrin cytoplasmic tails. Here, the cocrystal structure of the PTB domain of ICAP1 in complex with a 29-­amino-acid fragment (residues 170–198) of KRIT1 is presented to 1.7 Å resolution [the resolution at which 〈I/σ(I)〉 = 2.9 was 1.83 Å]. In previous studies, the structure of ICAP1 with integrin β1 was determined to 3.0 Å resolution and that of ICAP1 with the N-terminal portion of KRIT1 (residues 1–­198) was determined to 2.54 Å resolution; therefore, this study provides the highest resolution structure yet of ICAP1 and allows further detailed analysis of the interaction of ICAP1 with its minimal binding region in KRIT1. PMID:23695561

Quantifying protein-protein interactions in high throughput using protein domain microarrays.

PubMed

Kaushansky, Alexis; Allen, John E; Gordus, Andrew; Stiffler, Michael A; Karp, Ethan S; Chang, Bryan H; MacBeath, Gavin

2010-04-01

Protein microarrays provide an efficient way to identify and quantify protein-protein interactions in high throughput. One drawback of this technique is that proteins show a broad range of physicochemical properties and are often difficult to produce recombinantly. To circumvent these problems, we have focused on families of protein interaction domains. Here we provide protocols for constructing microarrays of protein interaction domains in individual wells of 96-well microtiter plates, and for quantifying domain-peptide interactions in high throughput using fluorescently labeled synthetic peptides. As specific examples, we will describe the construction of microarrays of virtually every human Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain, as well as microarrays of mouse PDZ domains, all produced recombinantly in Escherichia coli. For domains that mediate high-affinity interactions, such as SH2 and PTB domains, equilibrium dissociation constants (K(D)s) for their peptide ligands can be measured directly on arrays by obtaining saturation binding curves. For weaker binding domains, such as PDZ domains, arrays are best used to identify candidate interactions, which are then retested and quantified by fluorescence polarization. Overall, protein domain microarrays provide the ability to rapidly identify and quantify protein-ligand interactions with minimal sample consumption. Because entire domain families can be interrogated simultaneously, they provide a powerful way to assess binding selectivity on a proteome-wide scale and provide an unbiased perspective on the connectivity of protein-protein interaction networks.

Integrated electrokinetically driven microfluidic devices with pH-mediated solid-phase extraction coupled to microchip electrophoresis for preterm birth biomarkers.

PubMed

Sonker, Mukul; Knob, Radim; Sahore, Vishal; Woolley, Adam T

2017-07-01

Integration in microfluidics is important for achieving automation. Sample preconcentration integrated with separation in a microfluidic setup can have a substantial impact on rapid analysis of low-abundance disease biomarkers. Here, we have developed a microfluidic device that uses pH-mediated solid-phase extraction (SPE) for the enrichment and elution of preterm birth (PTB) biomarkers. Furthermore, this SPE module was integrated with microchip electrophoresis for combined enrichment and separation of multiple analytes, including a PTB peptide biomarker (P1). A reversed-phase octyl methacrylate monolith was polymerized as the SPE medium in polyethylene glycol diacrylate modified cyclic olefin copolymer microfluidic channels. Eluent for pH-mediated SPE of PTB biomarkers on the monolith was optimized using different pH values and ionic concentrations. Nearly 50-fold enrichment was observed in single channel SPE devices for a low nanomolar solution of P1, with great elution time reproducibility (<7% RSD). The monolith binding capacity was determined to be 400 pg (0.2 pmol). A mixture of a model peptide (FA) and a PTB biomarker (P1) was extracted, eluted, injected, and then separated by microchip electrophoresis in our integrated device with ∼15-fold enrichment. This device shows important progress towards an integrated electrokinetically operated platform for preconcentration and separation of biomarkers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using Geographical Information Systems to Explore Disparities in Preterm Birth Rates Among Foreign-born and U.S.-born Black Mothers

PubMed Central

Bloch, Joan Rosen

2012-01-01

Objective To examine spatial patterns of neighborhood contextual factors of stress with preterm birth (PTB) and nativity (foreign-born and U.S.-born) among Black mothers. Design Descriptive geographic-spatial research. Setting & Participants Births to Philadelphia residents during 2003–2005 in the context of Philadelphia residential neighborhoods (N = 350) were studied. Methods All data were aggregated to neighborhood levels (census tracts). Maps were created to assess geographic-spatial patterns. A geographic information system (GIS) database was created that imported geo-coded data on births, crime (assaults with guns and domestic abuse), poverty, race, and nativity (foreign-born vs. U.S.-born). Results Clear visual patterns of “bad” neighborhoods emerged and were significantly associated with higher prevalence of PTB for foreign-born Black and U.S.-born Black mothers (p < .0001). Conclusions This study demonstrated how GIS visually clarified important spatial patterns of adverse living conditions and PTB prevalence. Nurses can use GIS to better understand living environments of mothers and their families and to target interventions in geographical areas with the greatest service needs. Further research on individual and contextual factors is warranted to address the observed health disparities among the heterogeneous groups of foreign-born Black mothers. Despite limitations of aggregate data, it is clear that where mothers live matters. This has important implications for nursing practice and policy. PMID:22273411

Molecular insights into the specific recognition between the RNA binding domain qRRM2 of hnRNP F and G-tract RNA: A molecular dynamics study.

PubMed

Wang, Lingyun; Yan, Feng

2017-12-09

Heterogeneous nuclear ribonucleoprotein F (hnRNP F) controls the expression of various genes through regulating the alternative splicing of pre-mRNAs in the nucleus. It uses three quasi-RNA recognition motifs (qRRMs) to recognize G-tract RNA which contains at least three consecutive guanines. The structures containing qRRMs of hnRNP F in complex with G-tract RNA have been determined by nuclear magnetic resonance (NMR) spectroscopy, shedding light on the recognition mechanism of qRRMs with G-tract RNA. However, knowledge of the recognition details is still lacking. To investigate how qRRMs specifically bind with G-tract RNA and how the mutations of any guanine to an adenine in the G-tract affect the binding, molecular dynamics simulations with binding free energy analysis were performed based on the NMR structure of qRRM2 in complex with G-tract RNA. Simulation results demonstrate that qRRM2 binds strongly with G-tract RNA, but any mutation of the G-tract leads to a drastic reduction of the binding free energy. Further comparisons of the energetic components reveal that van der Waals and non-polar interactions play essential roles in the binding between qRRM2 and G-tract RNA, but the interactions are weakened by the effect of RNA mutations. Structural and dynamical analyses indicate that when qRRM2 binds with G-tract RNA, both qRRM2 and G-tract maintain stabilized structures and dynamics; however, the stability is disrupted by the mutations of the G-tract. These results provide novel insights into the recognition mechanism of qRRM2 with G-tract RNA that are not elucidated by the NMR technique. Copyright © 2017 Elsevier Inc. All rights reserved.

A Novel Mechanism of Estrogen Action in Breast Cancer Cells Mediated Through ER-FE65 Complex Formation

DTIC Science & Technology

2013-03-01

Deletion analyses mapped the ERα binding domain to the phosphotyrosine binding domain 2. Ectopic Fe65 increased the transcriptional activity of the...ERα in a PTB2 dependent manner in reporter assays. Fe65 knockdown decreased and its stable expression increased the activity of endogenous ERα in...Furthermore, Fe65 expression decreased the antagonistic activity of tamoxifen, suggesting a potential role for Fe65 in tamoxifen resistance. While a role of

Maternal and neonatal epidemiological features in clinical subtypes of preterm-birth

PubMed Central

Gimenez, Lucas G.; Krupitzki, Hugo B.; Momany, Allison M.; Gili, Juan A.; Poletta, Fernando A.; Campaña, Hebe; Cosentino, Viviana R.; Saleme, César; Pawluk, Mariela; Murray, Jeffrey C.; Castilla, Eduardo E.; Gadow, Enrique C.; Lopez-Camelo, Jorge S.

2016-01-01

Objective This study was designed to characterize and compare the maternal and newborn epidemiological characteristics through analysis of environmental factors, socio-demographic characteristics, and clinical characteristics between the different clinical subtypes of preterm birth (PTB): Idiopathic (PTB-I), premature rupture of the membranes (PTB-PPROM) and medically indicated (PTB-M). The two subtypes PTB-I and PTB-PPROM grouped are called spontaneous preterm births (PTB-S). Methods A retrospective, observational study was conducted in 1.291 preterm non-malformed singleton live-born children to nulliparous and multiparous mother’s in Tucumán-Argentina between 2005 and 2010. Over 50 maternal variables and ten newborn variables were compared between the different clinical subtypes. The comparisons were done to identify heterogeneity between subtypes of preterm birth: (PTB-S) vs. (PTB-M), and within spontaneous subtype: (PTB-I) vs. (PTB-PPROM). In the same way, two conditional logistic multivariate regressions were used to compare the odds ratio (OR) between PTB-S and PTB-M, as well as PTB-I and PTB-PPROM. We matched for maternal age when comparing maternal variables and gestational age when comparing infant variables. Results The PTB-I subtype was characterized by younger mothers of lower socioeconomic status, PTB-PPROM was characterized by environmental factors resulting from inflammatory processes, and PTB-M was characterized by increased maternal or fetal risk pregnancies. Conclusions The main risk factor for PTB-I and PTB-M was having had a prior preterm delivery, however previous spontaneous abortion was not a risk factor, suggesting a reproductive selection mechanism. PMID:26701680

Using geographical information systems to explore disparities in preterm birth rates among foreign-born and U.S.-born Black mothers.

PubMed

Bloch, Joan Rosen

2011-01-01

To examine spatial patterns of neighborhood contextual factors of stress with preterm birth (PTB) and nativity (foreign-born and U.S.-born) among Black mothers. Descriptive geographic-spatial research. Births to Philadelphia residents during 2003-2005 in the context of Philadelphia residential neighborhoods (N = 350) were studied. All data were aggregated to neighborhood levels (census tracts). Maps were created to assess geographic-spatial patterns. A geographic information system (GIS) database was created that imported geo-coded data on births, crime (assaults with guns and domestic abuse), poverty, race, and nativity (foreign-born vs. U.S.-born). Clear visual patterns of "bad" neighborhoods emerged and were significantly associated with higher prevalence of PTB for foreign-born Black and U.S.-born Black mothers (p < .0001). This study demonstrated how GIS visually clarified important spatial patterns of adverse living conditions and PTB prevalence. Nurses can use GIS to better understand living environments of mothers and their families and to target interventions in geographical areas with the greatest service needs. Further research on individual and contextual factors is warranted to address the observed health disparities among the heterogeneous groups of foreign-born Black mothers. Despite limitations of aggregate data, it is clear that where mothers live matters. This has important implications for nursing practice and policy. © 2011 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

The ShcA SH2 domain engages a 14-3-3/PI3'K signaling complex and promotes breast cancer cell survival.

PubMed

Ursini-Siegel, J; Hardy, W R; Zheng, Y; Ling, C; Zuo, D; Zhang, C; Podmore, L; Pawson, T; Muller, W J

2012-11-29

The ShcA adapter protein transmits activating signals downstream of receptor and cytoplasmic tyrosine kinases through the establishment of phosphotyrosine-dependent complexes. In this regard, ShcA possesses both a phosphotyrosine-binding domain (PTB) and Src homology 2 domain (SH2), which bind phosphotyrosine residues in a sequence-specific manner. Although the majority of receptor tyrosine kinases expressed in breast cancer cells bind the PTB domain, very little is known regarding the biological importance of SH2-driven ShcA signaling during mammary tumorigenesis. To address this, we employed transgenic mice expressing a mutant ShcA allele harboring a non-functional SH2 domain (ShcR397K) under the transcriptional control of the endogenous ShcA promoter. Using transplantation approaches, we demonstrate that SH2-dependent ShcA signaling within the mammary epithelial compartment is essential for breast tumor outgrowth, survival and the development of lung metastases. We further show that the ShcA SH2 domain activates the AKT pathway, potentially through a novel SH2-mediated complex between ShcA, 14-3-3ζ and the p85 regulatory subunit of phosphatidylinositol 3 (PI3') kinase. This study is the first to demonstrate that the SH2 domain of ShcA is critical for tumor survival during mammary tumorigenesis.

Hacking RNA: Hakai promotes tumorigenesis by switching on the RNA-binding function of PSF

PubMed Central

Figueroa, Angélica; Fujita, Yasuyuki; Gorospe, Myriam

2009-01-01

Hakai, an E3 ubiquitin ligase for the E-cadherin complex, plays a crucial role in lowering cell-cell contacts in epithelial cells, a hallmark feature of tumor progression. Recently, Hakai was also found to interact with PSF (PTB-associated splicing factor). While PSF can function as a DNA-binding protein with a tumor suppressive function, its association with Hakai promotes PSF’s RNA-binding ability and post-transcriptional influence on target mRNAs. Hakai overexpression enhanced the binding of PSF to mRNAs encoding cancer-related proteins, while knockdown of Hakai reduced the RNA-binding ability of PSF. Furthermore, the knockdown of PSF suppressed Hakai-induced cell proliferation. Thus, Hakai can affect the oncogenic phenotype both by altering E-cadherin-based intercellular adhesions and by increasing PSF’s ability to bind RNAs that promote cancer-related gene expression. PMID:19855157

PTB-associated splicing factor inhibits IGF-1-induced VEGF upregulation in a mouse model of oxygen-induced retinopathy.

PubMed

Dong, Lijie; Nian, Hong; Shao, Yan; Zhang, Yan; Li, Qiutang; Yi, Yue; Tian, Fang; Li, Wenbo; Zhang, Hong; Zhang, Xiaomin; Wang, Fei; Li, Xiaorong

2015-05-01

Pathological retinal neovascularization, including retinopathy of prematurity and age-related macular degeneration, is the most common cause of blindness worldwide. Insulin-like growth factor-1 (IGF-1) has a direct mitogenic effect on endothelial cells, which is the basis of angiogenesis. Vascular endothelial growth factor (VEGF) activation in response to IGF-1 is well documented; however, the molecular mechanisms responsible for the termination of IGF-1 signaling are still not completely elucidated. Here, we show that the polypyrimidine tract-binding protein-associated splicing factor (PSF) is a potential negative regulator of VEGF expression induced by IGF stimulation. Functional analysis demonstrated that ectopic expression of PSF inhibits IGF-1-stimulated transcriptional activation and mRNA expression of the VEGF gene, whereas knockdown of PSF increased IGF-1-stimulated responses. PSF recruited Hakai to the VEGF transcription complex, resulting in inhibition of IGF-1-mediated transcription. Transfection with Hakai siRNA reversed the PSF-mediated transcriptional repression of VEGF gene transcription. In summary, these results show that PSF can repress the transcriptional activation of VEGF stimulated by IGF-1 via recruitment of the Hakai complex and delineate a novel regulatory mechanism of IGF-1/VEGF signaling that may have implications in the pathogenesis of neovascularization in ocular diseases.

Multivalent DNA-binding properties of the HMG-1 proteins.

PubMed Central

Maher, J F; Nathans, D

1996-01-01

HMG-I proteins are DNA-binding proteins thought to affect the formation and function of transcription complexes. Each protein contains three DNA-binding motifs, known as AT-hooks, that bind in the minor groove of AT tracts in DNA. Multiple AT-hooks within a polypeptide chain should contact multiple AT tracts, but the rules governing these interactions have not been defined. In this study, we demonstrate that high-affinity binding uses two or three appropriately spaced AT tracts as a single multivalent binding site. These principles have implications for binding to regulatory elements such as the interferon beta enhancer, TATA boxes, and serum response elements. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8692884

Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population

PubMed Central

Gimenez, Lucas G.; Momany, Allison M.; Poletta, Fernando A.; Krupitzki, Hugo B.; Gili, Juan A.; Busch, Tamara D.; Saleme, Cesar; Cosentino, Viviana R.; Pawluk, Mariela S.; Campaña, Hebe; Gadow, Enrique C.; Murray, Jeffrey C.; Lopez-Camelo, Jorge S.

2017-01-01

Background Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. PTB is often classified according to clinical presentation: Idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and medically induced (PTB-M). The aim of this study was to evaluate the associations between specific candidate genes and clinical subtypes of PTB. Methods 24 SNPs were genotyped in 18 candidate genes in 709 infant triads. Of them, 243 were PTB-I, 256 PTB-PPROM, and 210 PTB-M. These data were analyzed with a Family-Based Association. Results PTB was nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, 3 SNPs were associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in CRHR1), rs610277 in F3 was associated with PTB-PPROM, and rs883319 in KCNN3 and rs610277 in F3 were associated with PTB-M. Conclusions Our study identified polymorphisms potentially associated with specific clinical subtypes of PTB in this Latin American population. These results could suggest a specific role of such genes in the mechanisms involved in each clinical subtype. Further studies are required to confirm our results and to determine the role of these genes in the pathophysiology of clinical subtypes. PMID:28426651

Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population.

PubMed

Gimenez, Lucas G; Momany, Allison M; Poletta, Fernando A; Krupitzki, Hugo B; Gili, Juan A; Busch, Tamara D; Saleme, Cesar; Cosentino, Viviana R; Pawluk, Mariela S; Campaña, Hebe; Gadow, Enrique C; Murray, Jeffrey C; Lopez-Camelo, Jorge S

2017-09-01

BackgroundPreterm birth (PTB) is the leading cause of neonatal mortality and morbidity. PTB is often classified according to clinical presentation as follows: idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and medically induced (PTB-M). The aim of this study was to evaluate the associations between specific candidate genes and clinical subtypes of PTB.MethodsTwenty-four single-nucleotide polymorphisms (SNPs) were genotyped in 18 candidate genes in 709 infant triads. Of them, 243 were PTB-I, 256 were PTB-PPROM, and 210 were PTB-M. These data were analyzed with a Family-Based Association.ResultsPTB was nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, three SNPs were associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in CRHR1), rs610277 in F3 was associated with PTB-PPROM, and rs883319 in KCNN3 and rs610277 in F3 were associated with PTB-M.ConclusionOur study identified polymorphisms potentially associated with specific clinical subtypes of PTB in this Latin American population. These results could suggest a specific role of such genes in the mechanisms involved in each clinical subtype. Further studies are required to confirm our results and to determine the role of these genes in the pathophysiology of clinical subtypes.

Evaluation of outpatients with suspected pulmonary tuberculosis in a high HIV prevalence setting in Ethiopia: clinical, diagnostic and epidemiological characteristics.

PubMed

Bruchfeld, Judith; Aderaye, Getachew; Palme, Ingela Berggren; Bjorvatn, Bjarne; Britton, Sven; Feleke, Yewenhareg; Källenius, Gunilla; Lindquist, Lars

2002-01-01

In a setting with a high prevalence of HIV we studied (i) the prevalence of pulmonary tuberculosis (PTB) and HIV; (ii) clinical and epidemiological characteristics of PTB; and (iii) the usefulness of standard procedures for diagnosing PTB. Of 509 consecutive outpatients evaluated on clinical suspicion of PTB in Addis Ababa, 33.0% were culture-verified as having PTB. PTB patients, non-TB patients and controls were HIV-1-positive in 57.1%, 38.5% and 8.3% of cases, respectively. Predictors for culture-verified PTB were age < 25 y, male gender and the presence of HIV and fever, whereas profound weight loss indicated HIV infection. Diagnosis of PTB based on clinical symptoms, sputum microscopy for acid-fast bacilli and chest radiography was sensitive (86.7%) but unspecific (64.1%). In HIV-positive patients both sensitivity and specificity were significantly lower (p < 0.05). HIV-related pulmonary infections are often misinterpreted as smear-negative PTB. HIV screening is therefore warranted not only in cases of verified TB but also as part of the diagnostic work-up in patients with respiratory symptoms suggestive of PTB. Also, increased awareness of, and improved diagnostic tools for, HIV-related pulmonary infections other than PTB are required, together with algorithms for patients with suspected PTB.

Interethnic mating and risk for preterm birth among Arab-American mothers: Evidence from the Arab-American Birth Outcomes Study

PubMed Central

El-Sayed, Abdulrahman M.; Galea, Sandro

2011-01-01

Arab ethnicity (AE) mothers have lower preterm birth (PTB) risk than white mothers. Little is known about the determinants of PTB among AE women or the role of interethnic mating in shaping PTB risk among this group. We assessed the relationship between interethnic mating and risk for PTB, very PTB, and late PTB among AE mothers. Data was collected for all births (N = 21,621) to AE women in Michigan between 2000 and 2005. Self-reported ancestry was used to determine paternal AE as well as to identify AE mothers. We used bivariate chi-square tests and multivariable logistic regression to assess the relationship between paternal non-AE and risk for PTB, very PTB, and late PTB among AE mothers. All analyses were also conducted among non-Arab white mothers as a control. Among AE mothers, paternal non-Arab ethnicity was associated with higher risk of PTB (OR = 1.18, 95% CI = 1.06, 1.30) and late PTB (OR = 1.24, 95% CI = 1.20, 1.38) compared to paternal Arab ethnicity. Paternal non-Arab ethnicity was not associated with risk for any outcome among non-Arab white mothers. Future studies could assess the causal mechanisms underlying the association between interethnic mating and risk for PTB. PMID:21042936

Interethnic mating and risk for preterm birth among Arab-American mothers: evidence from the Arab-American Birth Outcomes Study.

PubMed

El-Sayed, Abdulrahman M; Galea, Sandro

2011-06-01

Arab ethnicity (AE) mothers have lower preterm birth (PTB) risk than white mothers. Little is known about the determinants of PTB among AE women or the role of interethnic mating in shaping PTB risk among this group. We assessed the relationship between interethnic mating and risk for PTB, very PTB, and late PTB among AE mothers. Data was collected for all births (N = 21,621) to AE women in Michigan between 2000 and 2005. Self-reported ancestry was used to determine paternal AE as well as to identify AE mothers. We used bivariate chi-square tests and multivariable logistic regression to assess the relationship between paternal non-AE and risk for PTB, very PTB, and late PTB among AE mothers. All analyses were also conducted among non-Arab white mothers as a control. Among AE mothers, paternal non-Arab ethnicity was associated with higher risk of PTB (OR = 1.18, 95% CI = 1.06, 1.30) and late PTB (OR = 1.24, 95% CI = 1.20, 1.38) compared to paternal Arab ethnicity. Paternal non-Arab ethnicity was not associated with risk for any outcome among non-Arab white mothers. Future studies could assess the causal mechanisms underlying the association between interethnic mating and risk for PTB.

Non-canonical dynamic mechanisms of interaction between the p66Shc protein and Met receptor

PubMed Central

Landry, Mélissa; Pomerleau, Véronique; Saucier, Caroline

2016-01-01

Met receptor tyrosine kinase (RTK) is known to bind to the three distinct protein isoforms encoded by the ShcA (Shc) gene. Structure–function studies have unveiled critical roles for p52Shc-dependent signalling pathways in Met-regulated biological functions. The molecular basis of the interaction between the Met and p52Shc proteins is well-defined, but not for the longest protein isoform, p66Shc. In the present study, co-immunoprecipitation assays were performed in human embryonic kidney 293 (HEK293) cells, transiently co-transfected with Met and p66Shc mutants, in order to define the molecular determinants involved in mediating Met–p66Shc interaction. Our results show that p66Shc interacts constitutively with the receptor Met, and the Grb2 (growth factor receptor-bound protein-2) and Gab1 (Grb2-associated binder-1) adaptor proteins. Although its phosphotyrosine-binding domain (PTB) and Src homology 2 (SH2) domains co-ordinate p66Shc binding to non-activated Met receptor, these phosphotyrosine-binding modules, and its collagen homology domain 2 (CH2) region, exert negative constraints. In contrast, p66Shc interaction with the activated Met depends mainly on the integrity of its PTB domain, and to a lesser extent of its SH2 domain. Even though not required for the recruitment of p66Shc, tyrosine phosphorylation of p66Shc by activated Met enhances these interactions by mechanisms not reliant on the integrity of the Met multisubstrate-binding site. In turn, this increases phosphotyrosine-dependent p66Shc–Grb2–Gab1 complex formation away from the receptor, while blocking Grb2 and Gab1 recruitment to activated Met. In conclusion, we identify, for the first time, a novel non-canonical dynamic mode of interaction between Met and the p66 protein isoform of Shc and its effects on rewiring binding effector complexes according to the activation state of the receptor. PMID:27048591

Maternal Risk Factors for Preterm Birth in Murmansk County, Russia: A Registry-Based Study.

PubMed

Usynina, Anna A; Postoev, Vitaly A; Grjibovski, Andrej M; Krettek, Alexandra; Nieboer, Evert; Odland, Jon Øyvind; Anda, Erik Eik

2016-09-01

Globally, about 11% of all liveborn infants are preterm. To date, data on prevalence and risk factors of preterm birth (PTB) in Russia are limited. The aims of this study were to estimate the prevalence of PTB in Murmansk County, Northwestern Russia and to investigate associations between PTB and selected maternal factors using the Murmansk County Birth Registry. We conducted a registry-based study of 52 806 births (2006-2011). In total, 51 156 births were included in the prevalence analysis, of which 3546 were PTBs. Odds ratios with 95% confidence intervals of moderate-to-late PTB, very PTB and extremely PTB for a range of maternal characteristics were estimated using multinomial logistic regression, adjusting for potential confounders. The overall prevalence of PTB in Murmansk County was 6.9%. Unmarried status, prior PTBs, spontaneous and induced abortions were strongly associated with PTB at any gestational age. Maternal low educational level increased the risk of extremely and moderate-to-late PTB. Young (<18 years) or older (≥35 years) mothers, graduates of vocational schools, underweight, overweight/obese mothers, and smokers were at higher risk of moderate-to-late PTB. Secondary education, alcohol abuse, diabetes mellitus, or gestational diabetes were strongly associated with moderate-to-late and very PTB. The observed prevalence of PTB (6.9%) in Murmansk County, Russia was comparable with data on live PTB from European countries. Adverse prior pregnancy outcomes, maternal low educational level, unmarried status, alcohol abuse, and diabetes mellitus or gestational diabetes were the most common risk factors for PTB. © 2016 John Wiley & Sons Ltd.

Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study

PubMed Central

2013-01-01

Background Preterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known. Methods To identify common genetic variants predisposing to PTB, we genotyped 16 single nucleotide polymorphisms (SNPs) in the oxytocin (OXT), oxytocin receptor (OXTR), and leucyl/cystinyl aminopeptidase (LNPEP) genes in 651 case infants from the U.S. and one or both of their parents. In addition, we examined the role of rare genetic variation in susceptibility to PTB by conducting direct sequence analysis of OXTR in 1394 cases and 1112 controls from the U.S., Argentina, Denmark, and Finland. This study was further extended to maternal triads (maternal grandparents-mother of a case infant, N=309). We also performed in vitro analysis of selected rare OXTR missense variants to evaluate their functional importance. Results Maternal genetic effect analysis of the SNP genotype data revealed four SNPs in LNPEP that show significant association with prematurity. In our case–control sequence analysis, we detected fourteen coding variants in exon 3 of OXTR, all but four of which were found in cases only. Of the fourteen variants, three were previously unreported novel rare variants. When the sequence data from the maternal triads were analyzed using the transmission disequilibrium test, two common missense SNPs (rs4686302 and rs237902) in OXTR showed suggestive association for three gestational age subgroups. In vitro functional assays showed a significant difference in ligand binding between wild-type and two mutant receptors. Conclusions Our study suggests an association between maternal common polymorphisms in LNPEP and susceptibility to PTB. Maternal OXTR missense SNPs rs4686302 and rs237902 may have gestational age-dependent effects on prematurity. Most of the OXTR rare variants identified do not appear to significantly contribute to the risk of PTB, but those shown to affect receptor function in our in vitro study warrant further investigation. Future studies with larger sample sizes are needed to confirm the findings of this study. PMID:23889750

Analysis of DOK-6 function in downstream signaling of RET in human neuroblastoma cells.

PubMed

Kurotsuchi, Ai; Murakumo, Yoshiki; Jijiwa, Mayumi; Kurokawa, Kei; Itoh, Yasutomo; Kodama, Yoshinori; Kato, Takuya; Enomoto, Atsushi; Asai, Naoya; Terasaki, Hiroko; Takahashi, Masahide

2010-05-01

Point mutations and structural alterations of the RET tyrosine kinase gene cause multiple endocrine neoplasia type 2 (MEN 2) and papillary thyroid carcinoma, respectively. RET activation by glial cell line-derived neurotrophic factor (GDNF) is essential for the development of the enteric nervous system and the kidney. The signal through RET tyrosine kinase requires several adaptor proteins including the DOK (downstream of kinase) family of proteins. Of the seven members of the DOK protein family, DOK-1, -4, -5, and -6 have been reported to play roles in the GDNF-RET signaling pathway. Although DOK-6 has been shown to bind to RET and promote GDNF-induced neurite outgrowth in mouse Neuro2A cells, DOK-6 function in human cells remains unclear. In the present study, we investigated the role of DOK-6 in GDNF-RET signaling in human cells including neuroblastoma cells. DOK-6 was constitutively localized to the plasma membrane via its pleckstrin homology (PH) domain, and was phosphorylated following RET activation via a MEN2A mutation or GDNF stimulation. However, DOK-6 could not significantly affect downstream signaling and neurite outgrowth in human neuroblastoma cells. The binding affinity of the DOK-6 phosphotyrosine-binding (PTB) domain to RET was much lower than that of the DOK-1, DOK-4, and SHC PTB domains to RET. These findings indicate that DOK-6 is involved in RET signaling with less influence when compared with DOK-1, DOK-4, and SHC.

Changes in the Relationship Between Marriage and Preterm Birth, 1989–2006

PubMed Central

El-Sayed, Abdulrahman M.; Galea, Sandro

2011-01-01

Objective Maternal marriage has historically been protective against preterm birth (PTB); however, social norms and behaviors surrounding marriage have changed over time in the United States. We analyzed secular trends in the relationship between marriage and PTB. Methods We collected data about all births in Michigan between 1989 and 2006 to assess (1) the relationship between marital status and PTB and moderately PTB risk by year, and (2) the relationship between married and unmarried status and PTB and moderately PTB by year relative to similar marital status in 1989. Results Among nearly 2.4 million births between 1989 and 2006, PTB risk among married mothers increased while risk among unmarried mothers decreased. In adjusted models, married status became less protective against PTB relative to unmarried status over time by year, and was associated with higher risk of PTB over time. Moderately PTB risk increased among both married and unmarried groups, but more so among married mothers. Conclusion Our findings suggest that marriage is becoming less protective against PTB over time. The influence of social factors on risk for adverse birth outcomes is likely dynamic, suggesting that ongoing revisions to our understanding are in order. PMID:21886332

Increasing educational inequality in preterm birth in Quebec, Canada, 1981-2006.

PubMed

Auger, Nathalie; Roncarolo, Federico; Harper, Sam

2011-12-01

Few studies have evaluated the relationship between preterm birth (PTB) and maternal education over time. We sought to determine whether educational inequalities in PTB have increased in Québec, Canada. The authors analysed 2,124,909 singleton live births from 1981 to 2006, and computed the Relative Index of Inequality (RII) and Slope Index of Inequality (SII) with 95% CIs for the relationship between maternal education and extreme, very or moderate PTB (≤27, 28-31, and 32-36 completed weeks of gestation, respectively) for five periods (1981-1985, 1986-1990, 1991-1995, 1996-2000, 2001-2006), adjusting for maternal age, marital status, birthplace, language spoken at home, parity and infant sex. Average rates of extreme and moderate PTB increased over time but decreased for very PTB. A statistically significant increase in the RII over time was present for extreme and moderate PTB. The adjusted RII for extreme PTB increased from 1.58 (95% CI 1.24 to 2.01) in 1981-1985 to 3.11 (95% CI 2.54 to 3.81) in 2001-2006. For moderate PTB, the corresponding RIIs were 1.53 (95% CI 1.44 to 1.61) and 1.91 (95% CI 1.81 to 2.01). Absolute differences in the PTB proportion between the least and most educated mothers increased from 1981 to 2006 for extreme (adjusted SII 0.11% vs 0.28%) and moderate PTB (adjusted SII 1.67% vs 3.11%). Absolute differences in the proportion very PTB did not increase. Relative and absolute educational inequalities in extreme and moderate PTB have increased over time in Québec. Relative increases were largest for extreme PTB, and absolute increases were largest for moderate PTB.

Heightened circulating levels of antimicrobial peptides in tuberculosis—Diabetes co-morbidity and reversal upon treatment

PubMed Central

Kumar, Nathella Pavan; Moideen, Kadar; Viswanathan, Vijay; Sivakumar, Shanmugam; Menon, Pradeep A.; Kornfeld, Hardy

2017-01-01

Background The association of antimicrobial peptides (AMPs) with tuberculosis—diabetes comorbidity (PTB-DM) is not well understood. Methods To study the association of AMPs with PTB-DM, we examined the systemic levels of cathelicidin (LL37), human beta defensin– 2 (HBD2), human neutrophil peptides 1–3, (HNP1-3) and granulysin in individuals with either PTB-DM, PTB, latent TB (LTB) or no TB infection (NTB). Results Circulating levels of cathelicidin and HBD2 were significantly higher and granulysin levels were significantly lower in PTB-DM compared to PTB, LTB or NTB, while the levels of HNP1-3 were significantly higher in PTB-DM compared to LTB or NTB individuals. Moreover, the levels of cathelicidin and/or HBD2 were significantly higher in PTB-DM or PTB individuals with bilateral and cavitary disease and also exhibited a significant positive relationship with bacterial burden. Cathelidin, HBD2 and HNP1-3 levels exhibited a positive relationship with HbA1c and/or fasting blood glucose levels. Finally, anti-tuberculosis therapy resulted in significantly diminished levels of cathelicidin, HBD2, granulysin and significantly enhanced levels of HNP1-3 and granulysin in PTB-DM and/or PTB individuals. Conclusion Therefore, our data demonstrate that PTB-DM is associated with markedly enhanced levels of AMPs and diminished levels of granulysin. PMID:28910369

The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition.

PubMed

Tamayo, Joel V; Teramoto, Takamasa; Chatterjee, Seema; Hall, Traci M Tanaka; Gavis, Elizabeth R

2017-04-04

The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo's RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo's functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The Drosophila hnRNP F/H homolog glorund uses two distinct RNA-binding modes to diversify target recognition

DOE PAGES

Tamayo, Joel V.; Teramoto, Takamasa; Chatterjee, Seema; ...

2017-04-04

The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subsetmore » of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Lastly, our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.« less

The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamayo, Joel V.; Teramoto, Takamasa; Chatterjee, Seema

The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subsetmore » of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.« less

The Drosophila hnRNP F/H homolog glorund uses two distinct RNA-binding modes to diversify target recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamayo, Joel V.; Teramoto, Takamasa; Chatterjee, Seema

The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subsetmore » of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Lastly, our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.« less

Novel marker for the onset of frontotemporal dementia: early increase in activity-dependent neuroprotective protein (ADNP) in the face of Tau mutation.

PubMed

Schirer, Yulie; Malishkevich, Anna; Ophir, Yotam; Lewis, Jada; Giladi, Eliezer; Gozes, Illana

2014-01-01

Tauopathy, a major pathology in Alzheimer's disease, is also found in ~50% of frontotemporal dementias (FTDs). Tau transcript, a product of a single gene, undergoes alternative splicing to yield 6 protein species, each with either 3 or 4 microtubule binding repeat domains (tau 3R or 4R, associated with dynamic and stable microtubules, respectively). While the healthy human brain shows a 1/1 ratio of tau 3R/4R, this ratio may be dramatically changed in the FTD brain. We have previously discovered that activity-dependent neuroprotective protein (ADNP) is essential for brain formation in the mouse, with ADNP+/- mice exhibiting tauopathy, age-driven neurodegeneration and behavioral deficits. Here, in transgenic mice overexpressing a mutated tau 4R species, in the cerebral cortex but not in the cerebellum, we showed significantly increased ADNP expression (~3-fold transcripts) in the cerebral cortex of young transgenic mice (~disease onset), but not in the cerebellum, as compared to control littermates. The transgene-age-related increased ADNP expression paralleled augmented dynamic tau 3R transcript level compared to control littermates. Blocking mutated tau 4R transgene expression resulted in normalization of ADNP and tau 3R expression. ADNP was previously shown to be a member of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. Here, Brahma (Brm), a component of the SWI/SNF complex regulating alternative splicing, showed a similar developmental expression pattern to ADNP. Immunoprecipitations further suggested Brm-ADNP interaction coupled to ADNP - polypyrimidine tract-binding protein (PTB)-associated splicing factor (PSF)-binding, with PSF being a direct regulator of tau transcript splicing. It should be noted that although we have shown a correlation between levels of ADNP and tau isoform expression three months of age, we are not presenting evidence of a direct link between the two. Future research into ADNP/tau relations is warranted.

Periodontal bacteria in the genital tract: are they related to adverse pregnancy outcome?

PubMed

Cassini, M A; Pilloni, A; Condò, S G; Vitali, L A; Pasquantonio, G; Cerroni, L

2013-01-01

One of the most important factors implicated in preterm birth (PTB) is acute genitourinary tract infection. The bacteria causing chronic periodontal inflammation include Gram-negative rods and anaerobes similar to those found in women with bacterial vaginosis. The aim of this prospective study is to investigate the relationship between oral and vaginal microflora and preterm low birth weight. Real-time polymerase chain reaction was used to detect both the presence and level of six periodontitis-related species: Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Fusobacterium nucleatum ssp(Fn), and Prevotella intermedia (Pi) for both oral samples of subgingival plaque and cervical samples, obtained from 80 patients, during gynaecological examinations. The more representative oral pathogen (less than 60 percent) species in oral samples of preterm and term group were Tf, Td, and Fn. 24.4 percent of pregnant women presented periodontal pathogens in vaginal swab; the most representative species with a percentage over 0.1 percent of total bacteria in genital tract of preterm group were Tf, Td, and Piwith a positive correlation (less than 0.5). The presence of the bacterium T. denticolain the vagina, regardless of the amount, adversely affects preterm delivery.

Racial/Ethnic Inequities in Low Birth Weight and Preterm Birth: The Role of Multiple Forms of Stress.

PubMed

Almeida, Joanna; Bécares, Laia; Erbetta, Kristin; Bettegowda, Vani R; Ahluwalia, Indu B

2018-02-13

Introduction Racial/ethnic inequities in low birth weight (LBW) and preterm birth (PTB) persist in the United States. Research has identified numerous risk factors for adverse birth outcomes; however, they do not fully explain the occurrence of, or inequalities in PTB/LBW. Stress has been proposed as one explanation for differences in LBW and PTB by race/ethnicity. Methods Using the Pregnancy Risk Assessment Monitoring System (PRAMS) data from 2012 to 2013 for 21 states and one city (n = 15,915) we used Poisson regression to estimate the association between acute, financial and relationship stressors and LBW and PTB, and to examine the contribution of these stressors individually and simultaneously to racial/ethnic differences in LBW and PTB. Results Adjusting for age and race/ethnicity, acute (p < 0.001), financial (p < 0.001) and relationship (p < 0.05) stressors were associated with increased risk of LBW, but only acute (p < 0.05) and financial (p < 0.01) stress increased risk of PTB. Across all models, non-Hispanic blacks had higher risk of LBW and PTB relative to non-Hispanic whites (IRR 1.87, 95% CI 1.55, 2.27 and IRR 1.46, 95% CI 1.18, 1.79). Accounting for the effects of stressors attenuated the risk of LBW and PTB by 17 and 22% respectively, but did not fully explain the increased likelihood of LBW and PTB among non-Hispanic blacks. Discussion Results of this study demonstrate that stress may increase the risk of LBW and PTB. While stressors may contribute to racial/ethnic differences in LBW and PTB, they do not fully explain them. Mitigating stress during pregnancy may help promote healthier birth outcomes and reduce racial/ethnic inequities in LBW and PTB.

[Start of PTB (Phthisis) mortality statistics in Japan (1)].

PubMed

Shimao, Tadao

2008-12-01

First "Statistics Annual", which included the population and vital statistics was published in Japan in 1882, and the numbers of death classified by major causes of death were tabulated by sex and age groups and by prefecture. Koch R reported the discovery of tubercle bacilli as the pathogen for TB in 1882, and since the latter half of 1883, the numbers of death due to PTB (Phthisis) were tabulated by prefecture, and by sex and age groups since 1884 annually except for 1885. Based on the population statistics and the numbers of PTB death, PTB (Phthisis) mortality was calculated by sex and age groups, and the results were shown in Table 1. PTB mortality per 100,000 increased from 78.2 in 1884 to 171.9 in 1899. Sex- and age-specific PTB mortality in 1884 showed a pattern increasing with age, and the PTB mortality of male was higher than that of female in adult as shown in Fig. 2. In 1889, low peak of mortality was seen in the age groups 15-19 and 20-29, and in these age groups, the PTB mortality was higher in female than in male. Such trend was seen more markedly in 1894 and 1899, while the rate was higher in male than in female in the age groups over 40. Trend of PTB mortality by sex and age groups was shown in Fig. 3. Rapid increase of PTB mortality in the age groups 10-14 and 20-29 could be explained by the rapid increase of young women workers in fast growing silk and spinning industries, but how rapid increase of PTB mortality in infants be explained? In "Statistics Annual", PTB (Phthisis) mortality rate by prefecture was printed, and the summarized table was shown in Table 2. The rates in 1883 and 1884 were calculated from the numbers of PTB death and the B-type population shown in the "Statistics Annual", which will be described in the next issue of this paper.

Relationship between estimated pretest probability and accuracy of automated Mycobacterium tuberculosis assay in smear-negative pulmonary tuberculosis.

PubMed

Lim, T K; Gough, A; Chin, N K; Kumarasinghe, G

2000-09-01

The AMPLICOR assay (Roche; Branchburg, NJ), a rapid direct amplification test for Mycobacterium tuberculosis, has only been licensed for use in smear-positive respiratory specimens. However, many patients with pulmonary tuberculosis (PTB) have smear-negative disease. The clinical utility of this test in patients with smear-negative PTB is unknown. To evaluate the effect of pretest probability of PTB estimated by chest physicians on the accuracy of the AMPLICOR assay in patients with smear-negative PTB. A prospective study of consecutive patients suspected of having smear-negative PTB. Two chest physicians estimated the pretest probability of active disease (high, intermediate, and low categories). Respiratory specimens were examined with radiometric broth medium cultures and with the AMPLICOR assay for M tuberculosis. The decision on a final diagnosis of PTB was blinded to the AMPLICOR results. Active PTB was diagnosed in 25 of 441 patients (5.7%). The AMPLICOR assay had an overall sensitivity of 44% and a specificity of 99%. Results of the assay were negative in seven patients with culture-negative PTB. The proportions of patients in the high, intermediate, and low pretest groups were 4.5%, 19.7%, and 75.7%, respectively. The incidence of PTB for each group was 95%, 3.4%, and 0.9%, respectively. The sensitivities of the AMPLICOR assay in the three groups of patients were 47%, 33%, and 33%, respectively, while the specificities were 100%, 98%, and 99%, respectively. In patients suspected of having smear-negative PTB, the following conclusions were drawn: (1) the incidence of active PTB was low; (2) pretest estimates accurately discriminated between patients with high and low risk of PTB; (3) the risk of PTB was overestimated in the intermediate group; and (4) the utility of the AMPLICOR assay in the intermediate-risk group may be limited by the overestimation of disease prevalence and low test sensitivity. Further studies are needed on the role of the AMPLICOR assay in better selected patients with an intermediate risk of having smear-negative PTB.

Contribution of maternal age to preterm birth rates in Denmark and Quebec, 1981-2008.

PubMed

Auger, Nathalie; Hansen, Anne V; Mortensen, Laust

2013-10-01

We sought evidence to support the hypothesis that advancing maternal age is potentially causing a rise in preterm birth (PTB) rates in high-income countries. We assessed maternal age-specific trends in PTB using all singleton live births in Denmark (n = 1 674 308) and Quebec (n = 2 291 253) from 1981 to 2008. We decomposed the country-specific contributions of age-specific PTB rates and maternal age distribution to overall PTB rates over time. PTB rates increased from 4.4% to 5.0% in Denmark and from 5.1% to 6.0% in Quebec. Rates increased the most in women aged 20 to 29 years, whereas rates decreased or remained stable in women aged 35 years and older. The overall increase over time was driven by age-specific PTB rates, although the contribution of younger women was countered by fewer births at this age in both Denmark and Quebec. PTB rates increased among women aged 20 to 29 years, but their contribution to the overall PTB rates was offset by older maternal age over time. Women aged 20 to 29 years should be targeted to reduce PTB rates, as potential for prevention may be greater in this age group.

Muscarinic and alpha 1-adrenergic receptor binding characteristics of saw palmetto extract in rat lower urinary tract.

PubMed

Suzuki, Mayumi; Oki, Tomomi; Sugiyama, Tomomi; Umegaki, Keizo; Uchida, Shinya; Yamada, Shizuo

2007-06-01

To elucidate the in vitro and ex vivo effects of saw palmetto extract (SPE) on autonomic receptors in the rat lower urinary tract. The in vitro binding affinities for alpha 1-adrenergic, muscarinic, and purinergic receptors in the rat prostate and bladder were measured by radioligand binding assays. Rats received vehicle or SPE (0.6 to 60 mg/kg/day) orally for 4 weeks, and alpha 1-adrenergic and muscarinic receptor binding in tissues of these rats were measured. Saw palmetto extract inhibited specific binding of [3H]prazosin and [N-methyl-3H]scopolamine methyl chloride (NMS) but not alpha, beta-methylene adenosine triphosphate [2,8-(3)H]tetrasodium salt in the rat prostate and bladder. The binding activity of SPE for muscarinic receptors was four times greater than that for alpha 1-adrenergic receptors. Scatchard analysis revealed that SPE significantly reduced the maximal number of binding sites (Bmax) for each radioligand in the prostate and bladder under in vitro condition. Repeated oral administration of SPE to rats brought about significant alteration in Bmax for prostatic [3H]prazosin binding and for bladder [3H]NMS binding. Such alteration by SPE was selective to the receptors in the lower urinary tract. Saw palmetto extract exerts significant binding activity on autonomic receptors in the lower urinary tract under in vitro and in vivo conditions.

Severe Vitamin D Deficiency in HIV-infected Pregnant Women is Associated with Preterm Birth

PubMed Central

Jao, Jennifer; Freimanis, Laura; Mussi-Pinhata, Marisa M.; Cohen, Rachel A.; Monteiro, Jacqueline Pontes; Cruz, Maria Leticia; Branch, Andrea; Sperling, Rhoda S.; Siberry, George K.

2017-01-01

Background Low maternal vitamin D has been associated with preterm birth (PTB). HIV-infected pregnant women are at risk for PTB, but data on maternal vitamin D and PTB in this population is scarce. Methods In a cohort of Latin American HIV-infected pregnant women from the NICHD International Site Development Initiative (NISDI) protocol, we examined the association between maternal vitamin D status and PTB. Vitamin D status was defined as the following 25-hydroxyvitamin D levels: severe deficiency (<10 ng/mL), deficiency (10-20 ng/mL), insufficiency (21–29 ng/mL), and sufficiency (≥30 ng/mL). PTB was defined as delivery at <37 weeks gestational age (GA). Logistic regression was used to assess the association between maternal vitamin D status and PTB. Results Of 715 HIV-infected pregnant women, 13 (1.8%) were severely vitamin D deficient, 224 (31.3%) deficient, and 233 (32.6%) insufficient. Overall, 23.2% (166/715) of pregnancies resulted in PTB [median GA of PTBs =36 wks (interquartile range: 34-36)]. In multivariate analysis, severe vitamin D deficiency was associated with PTB [Odds Ratio=4.7, 95% Confidence Interval: 1.3-16.8)]. Conclusion Severe maternal vitamin D deficiency is associated with PTB in HIV-infected Latin American pregnant women. Further studies are warranted to determine if vitamin D supplementation in HIV-infected women may impact PTB. PMID:27716863

Analysis of alternative splicing associated with aging and neurodegeneration in the human brain

PubMed Central

Tollervey, James R.; Wang, Zhen; Hortobágyi, Tibor; Witten, Joshua T.; Zarnack, Kathi; Kayikci, Melis; Clark, Tyson A.; Schweitzer, Anthony C.; Rot, Gregor; Curk, Tomaž; Zupan, Blaž; Rogelj, Boris; Shaw, Christopher E.; Ule, Jernej

2011-01-01

Age is the most important risk factor for neurodegeneration; however, the effects of aging and neurodegeneration on gene expression in the human brain have most often been studied separately. Here, we analyzed changes in transcript levels and alternative splicing in the temporal cortex of individuals of different ages who were cognitively normal, affected by frontotemporal lobar degeneration (FTLD), or affected by Alzheimer's disease (AD). We identified age-related splicing changes in cognitively normal individuals and found that these were present also in 95% of individuals with FTLD or AD, independent of their age. These changes were consistent with increased polypyrimidine tract binding protein (PTB)–dependent splicing activity. We also identified disease-specific splicing changes that were present in individuals with FTLD or AD, but not in cognitively normal individuals. These changes were consistent with the decreased neuro-oncological ventral antigen (NOVA)–dependent splicing regulation, and the decreased nuclear abundance of NOVA proteins. As expected, a dramatic down-regulation of neuronal genes was associated with disease, whereas a modest down-regulation of glial and neuronal genes was associated with aging. Whereas our data indicated that the age-related splicing changes are regulated independently of transcript-level changes, these two regulatory mechanisms affected expression of genes with similar functions, including metabolism and DNA repair. In conclusion, the alternative splicing changes identified in this study provide a new link between aging and neurodegeneration. PMID:21846794

Clinical value of whole-blood interferon-gamma assay in patients with suspected pulmonary tuberculosis and AFB smear- and polymerase chain reaction-negative bronchial aspirates.

PubMed

Lee, Jaehee; Lee, Shin Yup; Yoo, Seung Soo; Cha, Seung Ick; Won, Dong Il; Park, Jae Yong; Lee, Won-Kil; Kim, Chang Ho

2012-07-01

Combining a polymerase chain reaction (PCR) test with bronchoscopy is frequently performed to allow a rapid diagnosis of smear-negative pulmonary tuberculosis (PTB). However, limited data are available concerning clinical judgment in patients with suspected PTB and AFB smear- and PCR-negative bronchial aspirates (BA). The present study evaluated the usefulness of whole-blood QuantiFERON-TB Gold In-Tube (QFT) testing in these patients. Of 166 patients with suspected PTB who had undergone bronchoscopy because of smear-negative sputum or inadequate sputum production, 93 (56%) were diagnosed with culture-positive PTB. Seventy-four patients were either AFB smear- or PCR-positive. In the 75 patients whose BA AFB smear and PCR results were both negative, 19 were finally diagnosed with PTB by culture. The QFT test had a negative predictive value of 91% for PTB. The QFT test may be useful for excluding PTB in patients with suspected PTB whose BA AFB smear and PCR results are both negative. Copyright © 2012 Elsevier Inc. All rights reserved.

Weighing the contributions of material and social area deprivation to preterm birth.

PubMed

Auger, Nathalie; Park, Alison L; Gamache, Philippe; Pampalon, Robert; Daniel, Mark

2012-09-01

Evidence suggests that individual socioeconomic status is a better predictor of preterm birth (PTB) than other individual social characteristics, but it is not clear if socioeconomic (material) area context is likewise more strongly related to PTB than social area characteristics. We compared material and social area deprivation to determine which was more strongly associated with PTB. Live singleton births from Québec, Canada were obtained for 1999-2006 (N = 581,898). PTB was defined as <37 completed gestational weeks. Two composite indices representing area-level material and social deprivation were used in Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI) for PTB, accounting for individual-level characteristics including maternal education. Results indicated that PTB rates were higher for areas with high material (7.1%) and social (6.8%) deprivation than those with low material (5.5%) and social (5.9%) deprivation. Adjusted hazards of PTB were slightly greater for material deprivation than social deprivation. These findings indicate that material area deprivation is marginally more strongly associated with PTB than social deprivation, but it is not clear that interventions to prevent PTB should focus on material deprivation any more than on social area deprivation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Parental occupation and preterm births: a nationwide epidemiological study in Sweden.

PubMed

Li, Xinjun; Sundquist, Jan; Kane, Kimberly; Jin, Qianren; Sundquist, Kristina

2010-11-01

The hypothesis was that some occupations could lead to preterm birth (PTB) because of potential exposures to various agents. The objective in this nationwide follow-up study was to analyse the association between PTB and parental occupational groups, controlling for potential confounders. Data from the Swedish Medical Birth Register, in which all children born in Sweden from 1990 onward are registered with their parents, were linked to census data. Inclusion criteria for the study population were employment (both women and men) and age >20 years (women). There were 816,743 first singleton live births from 1990 to 2004, of whom 43,956 were PTBs. A total of 7659 of the 43,956 PTBs were very PTBs. Odds ratios (ORs) with 95% confidence intervals were calculated separately for mothers and fathers to estimate the odds of PTB and very PTB in 51 occupational groups (reference groups: mothers or fathers who were 'Technical, science research-related workers and physicians') and by family income level. Women and men with low family incomes had increased ORs of PTB and very PTB. Significantly increased ORs of PTB (including very PTB) were found in four maternal and nine paternal occupational groups after accounting for family income, geographic region of residence, civil status, smoking habits, maternal age at infant's birth and period of birth. Further studies should examine specific agents in those parental occupations that were associated with increased odds of PTB and very PTB. © 2010 Blackwell Publishing Ltd.

Psychosocial Stress and Preterm Birth: The Impact of Parity and Race.

PubMed

Wheeler, Sarahn; Maxson, Pamela; Truong, Tracy; Swamy, Geeta

2018-03-29

Objectives Studies examining risk factors for preterm birth (PTB) such as psychosocial stress are often focused on women with a history of PTB; however, most preterm babies are born to women with no history of preterm birth. Our objective was to determine if the relationship between psychosocial stress and PTB is altered by parity. Non-Hispanic black (NHB) women have increased psychosocial stress and PTB; therefore, we further aimed to determine if race alters the relationship between psychosocial stress, parity, and PTB. Methods We performed a secondary analysis of the Healthy Pregnancy, Healthy Baby Study comparing pregnant women who were primiparous (first pregnancy), multiparous with history of preterm birth, or multiparous with history of term birth. Perceived stress, perceived racism, interpersonal support, John Henryism and self-efficacy were measured using validated instruments. Logistic regression was used to model the effect of psychosocial stress on PTB stratified by parity and race. Results The analysis entire cohort included 1606 subjects, 426 were primiparous, 268 had a history of presterm birth, and 912 had a history of term birth. In women with a history of term birth, higher self-efficacy was associated with lower odds of spontaneous PTB, and this association was amplified in NHB women. In women with a history of spontaneous PTB, John Henryism Active Coping was associated with lower odds of spontaneous PTB in the index pregnancy. Conclusions for Practice The relationship between psychosocial stress and PTB may be mediated by parity and race.

Reducing the global burden of Preterm Birth through knowledge transfer and exchange: a research agenda for engaging effectively with policymakers.

PubMed

Yamey, Gavin; Horváth, Hacsi; Schmidt, Laura; Myers, Janet; Brindis, Claire D

2016-03-18

Preterm birth (PTB) is the world's leading cause of death in children under 5 years. In 2013, over one million out of six million child deaths were due to complications of PTB. The rate of decline in child death overall has far outpaced the rate of decline attributable to PTB. Three key reasons for this slow progress in reducing PTB mortality are: (a) the underlying etiology and biological mechanisms remain unknown, presenting a challenge to discovering ways to prevent and treat the condition; (ii) while there are several evidence-based interventions that can reduce the risk of PTB and associated infant mortality, the coverage rates of these interventions in low- and middle-income countries remain very low; and (c) the gap between knowledge and action on PTB--the "know-do gap"--has been a major obstacle to progress in scaling up the use of existing evidence-based child health interventions, including those to prevent and treat PTB.In this review, we focus on the know-do gap in PTB as it applies to policymakers. The evidence-based approaches to narrowing this gap have become known as knowledge transfer and exchange (KTE). In our paper, we propose a research agenda for promoting KTE with policymakers, with an ambitious but realistic goal of reducing the global burden of PTB. We hope that our proposed research agenda stimulates further debate and discussion on research priorities to soon bend the curve of PTB mortality.

Diagnosis of smear-negative pulmonary tuberculosis based on clinical signs in the Republic of Congo.

PubMed

Linguissi, Laure Stella Ghoma; Vouvoungui, Christevy Jeannhey; Poulain, Pierre; Essassa, Gaston Bango; Kwedi, Sylvie; Ntoumi, Francine

2015-12-18

The diagnosis of pulmonary tuberculosis (PTB) and smear-negative pulmonary tuberculosis (SNPT) in resource-limited countries is often solely based on clinical signs, chest X-ray radiography and sputum smear microscopy. We investigated currently used methods for the routine diagnosis of SNPT in the Republic of Congo (RoC) among TB suspected patients. The specific case of HIV positive patients was also studied. A cross-sectional study was conducted at the anti-tuberculosis center (CAT) of Brazzaville, RoC. Tuberculosis suspects were examined for physical signs of TB. Clinical signs, results from sputum smear microscopy, tuberculin skin test (TST) and chest X-ray were recorded. Of the 772 enrolled participants, 372 were diagnosed PTB. Cough was a common symptom for PTB and no PTB patients. Pale skin, positive TST, weight loss and chest X-ray with abnormalities compatible with PTB (PTB-CXR) were significant indicators of PTB. Thirty-six percent of PTB patients were diagnosed SNPT. This category of patients presented less persistent cough and less PTB-CXR. Anorexia and asthenia were significant indicators of SNPT. In the case of HIV+ patients, 57% were SNPT with anorexia, asthenia and shorter cough being strong indicators of SNPT. Chest X-ray abnormalities, weight loss, pale skin and positive TST were significant indicators of PTB. Anorexia and asthenia showed good diagnostic performance for SNPT, which deserve to be recommended as index indicators of SNPT diagnosis. Duration of cough is also a relevant indicator, especially for HIV+ patients.

Association between maternal comorbidity and preterm birth by severity and clinical subtype: retrospective cohort study

PubMed Central

2011-01-01

Background Preterm birth (PTB) is a major cause of infant morbidity and mortality, but the relationship between comorbidity and PTB by clinical subtype and severity of gestational age remains poorly understood. We evaluated associations between maternal comorbidities and PTB by clinical subtype and gestational age. Methods We conducted a retrospective cohort study of 1,329,737 singleton births delivered in hospitals in the province of Québec, Canada, 1989-2006. PTB was classified by clinical subtype (medically indicated, preterm premature rupture of membranes (PPROM), spontaneous preterm labour) and gestational age (< 28, 28-31, 32-36 completed weeks). Odds ratios (OR) of PTB by clinical subtype for systemic and localized maternal comorbidities were estimated using polytomous logistic regression, adjusting for maternal age, grand multiparity, and period. Attributable fractions were calculated. Results PTB rates were higher among mothers with comorbidity (10.9%) compared to those without comorbidity (4.7%). Several comorbidities were associated with greater odds of medically indicated PTB compared with no comorbidity, but only comorbidities localized to the reproductive system were associated with spontaneous PTB. Drug dependence and mental disorders were strongly associated with PPROM and spontaneous PTBs across all gestational ages (OR > 2.0). At the population level, several major comorbidities (placental abruption, chorioamnionitis, oliogohydramnios, structural abnormality, cervical incompetence) were key contributors to all clinical subtypes of PTB, especially at < 32 weeks. Major systemic comorbidities (preeclampsia, anemia) were key contributors to PPROM and medically indicated PTBs. Conclusions The relationship between comorbidity and clinical subtypes of PTB depends on gestational age. Prevention of PPROM and spontaneous PTB may benefit from greater attention to preeclampsia, anemia and comorbidities localized to the reproductive system. PMID:21970736

Association between maternal comorbidity and preterm birth by severity and clinical subtype: retrospective cohort study.

PubMed

Auger, Nathalie; Le, Thi Uyen Nhi; Park, Alison L; Luo, Zhong-Cheng

2011-10-04

Preterm birth (PTB) is a major cause of infant morbidity and mortality, but the relationship between comorbidity and PTB by clinical subtype and severity of gestational age remains poorly understood. We evaluated associations between maternal comorbidities and PTB by clinical subtype and gestational age. We conducted a retrospective cohort study of 1,329,737 singleton births delivered in hospitals in the province of Québec, Canada, 1989-2006. PTB was classified by clinical subtype (medically indicated, preterm premature rupture of membranes (PPROM), spontaneous preterm labour) and gestational age (< 28, 28-31, 32-36 completed weeks). Odds ratios (OR) of PTB by clinical subtype for systemic and localized maternal comorbidities were estimated using polytomous logistic regression, adjusting for maternal age, grand multiparity, and period. Attributable fractions were calculated. PTB rates were higher among mothers with comorbidity (10.9%) compared to those without comorbidity (4.7%). Several comorbidities were associated with greater odds of medically indicated PTB compared with no comorbidity, but only comorbidities localized to the reproductive system were associated with spontaneous PTB. Drug dependence and mental disorders were strongly associated with PPROM and spontaneous PTBs across all gestational ages (OR > 2.0). At the population level, several major comorbidities (placental abruption, chorioamnionitis, oliogohydramnios, structural abnormality, cervical incompetence) were key contributors to all clinical subtypes of PTB, especially at < 32 weeks. Major systemic comorbidities (preeclampsia, anemia) were key contributors to PPROM and medically indicated PTBs. The relationship between comorbidity and clinical subtypes of PTB depends on gestational age. Prevention of PPROM and spontaneous PTB may benefit from greater attention to preeclampsia, anemia and comorbidities localized to the reproductive system.

Effect of different ripening stages on walnut kernel quality: antioxidant activities, lipid characterization and antibacterial properties.

PubMed

Amin, Furheen; Masoodi, F A; Baba, Waqas N; Khan, Asma Ashraf; Ganie, Bashir Ahmad

2017-11-01

Packing tissue between and around the kernel halves just turning brown (PTB) is a phenological indicator of kernel ripening at harvest in walnuts. The effect of three ripening stages (Pre-PTB, PTB and Post-PTB) on kernel quality characteristics, mineral composition, lipid characterization, sensory analysis, antioxidant and antibacterial activity were investigated in fresh kernels of indigenous numbered walnut selection of Kashmir valley "SKAU-02". Proximate composition, physical properties and sensory analysis of walnut kernels showed better results for Pre-PTB and PTB while higher mineral content was seen for kernels at Post-PTB stage in comparison to other stages of ripening. Kernels showed significantly higher levels of Omega-3 PUFA (C18:3 n3 ) and low n6/n3 ratio when harvested at Pre-PTB and PTB stages. The highest phenolic content and antioxidant activity was observed at the first stage of ripening and a steady decrease was observed at later stages. TBARS values increased as ripening advanced but did not show any significant difference in malonaldehyde formation during early ripening stages whereas it showed marked increase in walnut kernels at post-PTB stage. Walnut extracts inhibited growth of Gram-positive bacteria ( B. cereus, B. subtilis, and S. aureus ) with respective MICs of 1, 1 and 5 mg/mL and gram negative bacteria ( E. coli, P. and K. pneumonia ) with MIC of 100 mg/mL. Zone of inhibition obtained against all the bacterial strains from walnut kernel extracts increased with increase in the stage of ripening. It is concluded that Pre-PTB harvest stage with higher antioxidant activities, better fatty acid profile and consumer acceptability could be preferred harvesting stage for obtaining functionally superior walnut kernels.

Severe Vitamin D Deficiency in Human Immunodeficiency Virus-Infected Pregnant Women is Associated with Preterm Birth.

PubMed

Jao, Jennifer; Freimanis, Laura; Mussi-Pinhata, Marisa M; Cohen, Rachel A; Monteiro, Jacqueline Pontes; Cruz, Maria Leticia; Branch, Andrea; Sperling, Rhoda S; Siberry, George K

2017-04-01

Background  Low maternal vitamin D has been associated with preterm birth (PTB). Human immunodeficiency virus (HIV)-infected pregnant women are at risk for PTB, but data on maternal vitamin D and PTB in this population are scarce. Methods  In a cohort of Latin American HIV-infected pregnant women from the National Institute of Child Health and Human Development International Site Development Initiative protocol, we examined the association between maternal vitamin D status and PTB. Vitamin D status was defined as the following 25-hydroxyvitamin D levels: severe deficiency (< 10 ng/mL), deficiency (10-20 ng/mL), insufficiency (21-29 ng/mL), and sufficiency (≥30 ng/mL). PTB was defined as delivery at < 37 weeks' gestational age (GA). Logistic regression was used to assess the association between maternal vitamin D status and PTB. Results  Of 715 HIV-infected pregnant women, 13 (1.8%) were severely vitamin D deficient, 224 (31.3%) were deficient, and 233 were (32.6%) insufficient. Overall, 23.2% (166/715) of pregnancies resulted in PTB (median GA of PTBs = 36 weeks [interquartile range: 34-36]). In multivariate analysis, severe vitamin D deficiency was associated with PTB (odds ratio = 4.7, 95% confidence interval: 1.3-16.8]). Conclusion  Severe maternal vitamin D deficiency is associated with PTB in HIV-infected Latin American pregnant women. Further studies are warranted to determine if vitamin D supplementation in HIV-infected women may impact PTB. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Gestational age-dependent risk factors for preterm birth: associations with maternal education and age early in gestation.

PubMed

Auger, Nathalie; Abrahamowicz, Michal; Wynant, Willy; Lo, Ernest

2014-05-01

Preterm birth (PTB) before 37 weeks can occur over a wide range of gestational ages, but few studies have assessed if associations between risk factors and PTB vary over the duration of gestation. We sought to evaluate if associations between two major risk factors (maternal education and age) and PTB depend on gestational age at delivery. We estimated hazard ratios of PTB for education and age in a time-to-event analysis using a retrospective cohort of 223,756 live singleton births from the province of Québec, Canada for the years 2001-2005. Differences in hazards of maternal education and age with PTB were assessed over gestational age in a Cox proportional hazards model using linear and nonlinear time interaction terms, adjusting for maternal characteristics. Associations of PTB with lower (vs. higher) education and older (vs. younger) age strengthened progressively at earlier gestational ages, such that the risk of PTB for maternal education and age was not constant over the course of gestation. Associations of PTB with risk factors such as maternal low education and older age may be stronger early in gestation. Models that capture the time-dependent nature of PTB may be useful when the goal is to assess associations at low gestational ages, and to avoid masked or biased associations early in gestation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of bisoprolol and losartan treatment in the hypertrophic and failing right heart.

PubMed

Andersen, Stine; Schultz, Jacob Gammelgaard; Andersen, Asger; Ringgaard, Steffen; Nielsen, Jan M; Holmboe, Sarah; Vildbrad, Mads D; de Man, Frances S; Bogaard, Harm J; Vonk-Noordegraaf, Anton; Nielsen-Kudsk, Jens Erik

2014-11-01

Sympathetic adrenergic stimulation and the renin-angiotensin-aldosterone system are highly elevated in right heart failure. We evaluated if treatment with the adrenergic receptor blocker bisoprolol or the angiotensin II receptor blocker losartan could prevent the progression of right ventricular (RV) hypertrophy and failure in rats after pulmonary trunk banding (PTB). Male Wistar rats were randomized to severe PTB with a 0.5-mm banding clip (PTB0.5, n = 29), moderate PTB with a 0.6-mm banding clip (PTB0.6, n = 28), or sham operation (SHAM, n = 13). The PTB0.5 and PTB0.6 rats were randomized to 6 weeks of 10 mg/kg/d bisoprolol treatment, 20 mg/kg/d losartan treatment, or vehicle treatment. The PTB caused hypertrophy, dilation, and reduced function of the RV in all rats subjected to the procedure. Rats subjected to the more severe banding developed decompensated RV failure with extracardiac manifestations. Treatment with bisoprolol slowed the heart rate, and treatment with losartan lowered mean arterial pressure, confirming adequate dosing, but none of the treatments improved RV function or arrested the progression of RV hypertrophy and failure compared with vehicle. In our PTB model of pressure overload-induced RV hypertrophy and failure, treatment with bisoprolol and losartan did not demonstrate any beneficial effects in compensated or decompensated RV failure. Copyright © 2014 Elsevier Inc. All rights reserved.

Significant decline in the tuberculosis burden in the Philippines ten years after initiating DOTS.

PubMed

Tupasi, T E; Radhakrishna, S; Chua, J A; Mangubat, N V; Guilatco, R; Galipot, M; Ramos, G; Quelapio, M I D; Beltran, G; Legaspi, J; Vianzon, R G; Lagahid, J

2009-10-01

The Philippines ranks ninth among the 22 high-burden countries for tuberculosis (TB). To measure the burden of pulmonary tuberculosis (PTB) in the Philippines and determine the impact of the DOTS strategy. The 2007 nationwide TB prevalence survey covered 50 clusters selected by multi-stage stratified random sampling from Metro Manila and other urban and rural areas. Subjects aged >or=10 years were screened radiographically for PTB to identify subjects for sputum examination and determine the prevalence of bacteriologically confirmed PTB, i.e., smear- and/or culture-positive PTB. In subjects aged >or=10 years, the 2007 prevalence of radiographic PTB was 6.3% (95%CI 5.5-7.1), bacteriologically confirmed PTB was 6.6 per 1000 (95%CI 5.1-8.1) and sputum smear-positive PTB was 2.6/1000 (95%CI 1.7-3.6). For the total population, the corresponding estimates were respectively 4.7%, 4.9/1000 and 2.0/1000. Between 1997 and 2007, there was a 31% reduction in bacteriologically confirmed PTB (P < 0.02) and a 27% reduction in smear-positive PTB (P = 0.18). This decline occurred despite the increasing poverty in the population. The survey demonstrated a significant decline in the TB burden 10 years after the implementation of DOTS, facilitated by a strategic public-private partnership.

Modifiable factors associated with active pulmonary tuberculosis in a Kenyan prison.

PubMed

Amwayi, A S; Kikuvi, G M; Muchiri, E M

2010-02-01

To establish modifiable factors associated with active pulmonary tuberculosis (PTB) among prisoners. Retrospective matched case-control study. Nakuru GK prison in Kenya. A total of 144 subjects (48 cases and 96 controls) were recruited into the study. Cases were adult prisoners who had at least two initial sputum specimens being Acid Fast Bacilli-positive (AFB+) on direct smear microscopy and hence recruited to PTB WHO DOTS Programme. Controls were adults with no chronic cough and not on PTB treatment six months prior to the study. Independent factors significantly associated with active PTB disease were: self reported HIV+ status (OR=11; 95% CI = 2.42-47.77), evidence of BCG vaccination (OR = 0.20; 95% CI = 0.05-0.60), contact with PTB case (OR = 7.0; 95% CI = 1.17-38.23), unemployment (OR = 9.0; 95% CI = 1.84-43.97) and sharing linen (OR = 4.32; 95%CI = 1.08-17.29). Modifiable factors associated with active PTB in Nakuru G.K prison are: HIV status, BCG vaccination, PTB case contact, poverty and poor personal hygiene. We recommend HIV counselling and testing of all PTB patients, screening for TB upon prison entry and TB contact investigation and improving personal hygiene of prisoners.

Prevalence, Characteristics, Management, and Outcome of Pulmonary Tuberculosis in HIV-Infected Children in the TREAT Asia Pediatric HIV Observational Database (TApHOD)

PubMed Central

Sudjaritruk, Tavitiya; Maleesatharn, Alan; Prasitsuebsai, Wasana; Fong, Siew Moy; Le, Ngoc Oanh; Le, Thanh Thuy Thi; Lumbiganon, Pagakrong; Kumarasamy, Nagalingeswaran; Kurniati, Nia; Hansudewechakul, Rawiwan; Yusoff, Nik Khairulddin Nik; Razali, Kamarul Azahar Mohd; Kariminia, Azar; Sohn, Annette H.

2013-01-01

Abstract A multicenter, retrospective, observational study was conducted to determine prevalence, characteristics, management, and outcome of pulmonary tuberculosis (PTB) in Asian HIV-infected children in the TREAT Asia Pediatric HIV Observational Database (TApHOD). Data on PTB episodes diagnosed during the period between 12 months before antiretroviral therapy (ART) initiation and December 31, 2009 were extracted. A total of 2678 HIV-infected children were included in TApHOD over a 13-year period; 457 developed PTB, giving a period prevalence of 17.1% (range 5.7–33.0% per country). There were a total of 484 PTB episodes; 27 children had 2 episodes each. There were 21 deaths (4.3%). One third of episodes (n=175/484) occurred after ART initiation at a median of 14.1 months (interquartile range [IQR] 2.5–28.8 months). The median (IQR) CD4+ values were 9.0% (3.0–16.0%) and 183.5 (37.8–525.0) cells/mm3 when PTB was diagnosed. Most episodes (n=424/436, 97.3%) had abnormal radiographic findings compatible with PTB, whereas half (n=267/484, 55.2%) presented with clinical characteristics of PTB. One third of those tested (n=42/122, 34.4%) had bacteriological evidence of PTB. Of the 156 episodes (32.2%) that were accompanied with extrapulmonary TB, pleuritis was the most common manifestation (81.4%). After treatment completion, most episodes (n=396/484, 81.9%) were recorded as having positive outcomes (cured, treatment completed and child well, and improvement). The prevalence of PTB among Asian HIV-infected children in our cohort was high. Children with persistent immunosuppression remain vulnerable to PTB even after ART initiation. PMID:24206012

Effects of dust storm events on weekly clinic visits related to pulmonary tuberculosis disease in Minqin, China

NASA Astrophysics Data System (ADS)

Wang, Yun; Wang, Ruoyu; Ming, Jing; Liu, Guangxiu; Chen, Tuo; Liu, Xinfeng; Liu, Haixia; Zhen, Yunhe; Cheng, Guodong

2016-02-01

Pulmonary tuberculosis (PTB) is a major public health problem in China. Minqin, a Northwest county of China, has a very high number of annual PTB clinic visits and it is also known for its severe dust storms. The epidemic usually begins in February and ends in July, while the dust storms mainly occur throughout spring and early summer, thereby suggesting that there might be a close link between the causative agent of PTB and dust storms. We investigated the general impact of dust storms on PTB over time by analyzing the variation in weekly clinic visits in Minqin during 2005-2012. We used the Mann-Whitney-Pettitt test and a regression model to determine the seasonal periodicity of PTB and dust storms in a time series, as well as assessing the relationships between meteorological variables and weekly PTB clinic visits. After comparing the number of weekly PTB cases in Gansu province with dust storm events, we detected a clear link between the population dynamics of PTB and climate events, i.e., the onset of epidemics and dust storms (defined by an atmospheric index) occurred in almost the same mean week. Thus, particulate matter might be the cause of PTB outbreaks on dust storm days. It is highly likely that the significant decline in annual clinic visits was closely associated with improvements in the local environment, which prevented desertification and decreased the frequency of dust storm events. To the best of our knowledge, this is the first population-based study to provide clear evidence that a PTB epidemic was affected by dust storms in China, which may give insights into the association between this environmental problem and the evolution of epidemic disease.

Increased TLR4 and TREM-1 expression on monocytes and neutrophils in preterm birth: further evidence of a proinflammatory state.

PubMed

Yan, Huan; Li, Hong; Zhu, Linlin; Gao, Junjun; Li, Pengyun; Zhang, Zhan

2018-03-25

Increased inflammation is considered as a risk factor and a promoter of preterm birth (PTB). Monocytes and neutrophils are the main sources of cytokines in the early inflammatory phase. So far, very few studies have indicated CD14/TLR4 and TREM-1 on the monocytes and neutrophils as important targets in PTB. TLR4 and TREM-1 on CD14 + maternal and cord blood monocytes and neutrophils were detected using flow cytometry in 48 normal term women, 48 PTB with chorioamnionitis (CCA) women, and 40 PTB without CCA women. In the fetal membranes, mRNA and protein levels of the CD14/TLR4-TREM-1 signaling pathway, CD14, TLR4, NF-κBp65, and TREM-1 were analyzed by qRT-PCR and western blot. ELISA was further used to detect TLR4 and TREM-1 levels in maternal and cord serums. Compared with the normal term and PTB without CCA women, we found that (1) TLR4 and TREM-1 levels on CD14 + maternal and cord blood monocytes and neutrophils in the PTB with CCA group were elevated (p < .001); (2) the protein and mRNA expressions of CA14, TLR4, NF-κBp65, and TREM-1 of the PTB with CCA group were upregulated (p < .001); (3) Maternal and cord serum concentrations of TLR4 and TREM-1 in the PTB with CCA group were greater (p < .001). The high levels of TLR4 and TREM-1 surface expression were observed on CD14 + maternal and cord blood monocyte and neutrophils, confirming their proinflammatory profiles in PTB with CCA. TLR4 and TREM-1 on monocyte and neutrophils might have a role in infection-related PTB.

Investigating the Et-1/SphK/S1P Pathway as a Novel Approach for the Prevention of Inflammation-Induced Preterm Birth.

PubMed

Giusto, Kiersten; Ashby, Charles R

2018-01-30

Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, occurs in up to 18 percent of births worldwide and accounts for the majority of perinatal morbidity and mortality. While the single most common cause of PTB has been identified as inflammation, safe and effective pharmacotherapy to prevent PTB has yet to be developed. Our group has used an in vivo model of inflammation driven PTB, biochemical methods, pharmacological approaches, a novel endothelin receptor antagonist that we synthesized and RNA knockdown to help establish the role of endothelin-1 (ET-1) in inflammation-associated PTB. Further, we have used our in vivo model to test whether sphingosine kinase, which acts downstream of ET-1, plays a role in PTB. We have shown that levels of endothelin converting enzyme-1 (ECE-1) and ET-1 are increased when PTB is induced in timed pregnant mice with lipopolysaccharide (LPS) and that blocking ET-1 action, pharmacologically or using ECE-1 RNA silencing, rescues LPS-induced mice from PTB. ET-1 activates the sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) pathway. S1P, in turn, is an important signaling molecule in the pro-inflammatory response. Interestingly, we have shown that SphK inhibition also prevents LPS-induced PTB in timed pregnant mice. Further, we showed that SphK inhibition suppresses the ECE-1/ET-1 axis, implicating positive feedback regulation of the SphK/S1P/ECE-1/ET-1 axis. The ET-1/SphK/SIP pathway is a potential pharmacotherapeutic target for the prevention of PTB. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dental caries and preterm birth: a systematic review and meta-analysis

PubMed Central

D’Antonio, Francesco; Reierth, Eirik; Basnet, Purusotam; Trovik, Tordis A; Orsini, Giovanna; Manzoli, Lamberto; Acharya, Ganesh

2018-01-01

Objectives The primary objective of this systematic review was to evaluate the association between dental caries and preterm birth (PTB). The secondary objective was ascertaining the difference between women with dental caries who experienced PTB and those who did not with regard to decayed, missing and filled teeth (DMFT), and decayed, missing and filled surfaces (DMFS) indices. Methods MEDLINE, Embase, CINAHL and Cochrane databases were searched initially in November 2015 and repeated in December 2016. We included observational cohort and case–control studies. Only studies reporting the risk of PTB in women affected compared with those not affected by dental caries in pregnancy were included. Random-effect meta-analyses were used to compute the summary OR of PTB among women with caries versus women without caries, and the mean difference in either DMFT or DMFS indices between women experiencing PTB and those without PTB. Results Nine observational studies (4826 pregnancies) were included. Women affected by dental caries during pregnancy did not show a significantly higher risk of PTB (OR: 1.16, 95% CI 0.90 to 1.49, P=0.25, I2=35%). Also, the women with PTB did not show significantly higher DMFT or DMFS indices (summary mean differences: 1.56, P=0.10; I2=92% and −0.15, P=0.9, I2=89%, respectively). Conclusion Dental caries does not appear to be a substantial risk factor for PTB. Trial registration number NCT01675180; Pre-results. PMID:29500202

Differential effects of stress and African ancestry on preterm birth and related traits among US born and immigrant Black mothers.

PubMed

Tsai, Hui-Ju; Surkan, Pamela J; Yu, Stella M; Caruso, Deanna; Hong, Xiumei; Bartell, Tami R; Wahl, Anastacia D; Sampankanpanich, Claire; Reily, Anne; Zuckerman, Barry S; Wang, Xiaobin

2017-02-01

Preterm birth (PTB, <37 weeks of gestation) is influenced by a wide range of environmental, genetic and psychosocial factors, and their interactions. However, the individual and joint effects of genetic factors and psychosocial stress on PTB have remained largely unexplored among U.S. born versus immigrant mothers.We studied 1121 African American women from the Boston Birth Cohort enrolled from 1998 to 2008. Regression-based analyses were performed to examine the individual and joint effects of genetic ancestry and stress (including lifetime stress [LS] and stress during pregnancy [PS]) on PTB and related traits among U.S. born and immigrant mothers.Significant associations between LS and PTB and related traits were found in the total study population and in immigrant mothers, including gestational age, birthweight, PTB, and spontaneous PTB; but no association was found in U.S. born mothers. Furthermore, significant joint associations of LS (or PS) and African ancestral proportion (AAP) on PTB were found in immigrant mothers, but not in U.S. born mothers.Although, overall, immigrant women had lower rates of PTB compared to U.S. born women, our study is one of the first to identify a subset of immigrant women could be at significantly increased risk of PTB and related outcomes if they have high AAP and are under high LS or PS. In light of the growing number of immigrant mothers in the U.S., our findings may have important clinical and public health implications.

Distribution and density of substance P receptors in the feline gastrointestinal tract using autoradiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothstein, R.D.; Johnson, E.; Ouyang, A.

1991-06-01

Autoradiography was used to localize and quantify substance P receptors in the feline gastrointestinal tract. The specific binding of {sup 125}I-Bolton Hunter substance P was determined in the esophagus, lower esophageal sphincter, antrum, pylorus, duodenum, jejunum, ileum, ileocecal sphincter, and colon. Competitive binding studies indicated that substance P binding sites or NK-1 receptor sites were demonstrated. The concentration of NK-1 receptors was greatest in the distal half of the gastrointestinal tract, with the highest concentrations in the proximal colon. The circular muscle layer contained the greatest amount of substance P binding. The location and density of binding sites for substancemore » P may be important in understanding the relative importance of both the pharmacological responses to this neuropeptide and the immunohistochemical evidence of the peptide at different sites in the intestine.« less

Sealing Penetrating Eye Injuries Using Photoactivated Bonding

DTIC Science & Technology

2012-09-01

membrane over a penetrating corneal injury with photochemical tissue bonding ( PTB )(Task 1), we had proposed to directly bond, with PTB , the edges of...wounds with irregular shapes which mimic traumatic wounds. We had previously demonstrated that PTB effectively sealed linear incisional wounds in...developed for sealing eyelid lacerations with PTB was submitted in Year 2 and was published in Year 3 in Lasers in Surgery and Medicine. It is listed in

The Microbiome and Complement Activation: A Mechanistic Model for Preterm Birth

PubMed Central

Dunn, Alexis B.; Dunlop, Anne L.; Hogue, Carol J.; Miller, Andrew; Corwin, Elizabeth J.

2018-01-01

Preterm Birth (PTB, < 37 completed weeks' gestation) is one of the leading obstetrical problems in the United States affecting approximately 1 of every 9 births. Even more concerning are the persistent racial disparities in PTB with particularly high rates in African Americans. There are several recognized pathophysiologic pathways to PTB, including infection and/or exaggerated systemic or local inflammation. Intrauterine infection is a causal factor linked to PTB, thought to result most commonly from inflammatory processes triggered by microbial invasion of bacteria ascending from the vaginal microbiome. Trials to treat various infections have shown limited efficacy in reducing PTB risk, suggesting that other complex mechanisms, including those associated with inflammation, may be involved in the relationship between microbes, infection, and PTB. A key mediator of the inflammatory response, and recently shown to be associated with PTB, is the complement system, an innate defense mechanism involved in both normal physiologic processes that occur during pregnancy implantation, as well as processes that promote the elimination of pathogenic microbes. The purpose of this paper is to present a mechanistic model of inflammation-associated PTB, which hypothesizes a relationship between the microbiome and dysregulation of the complement system. Exploring the relationships between the microbial environment and complement biomarkers may elucidate a potentially modifiable biological pathway to preterm birth. PMID:28073296

A Proposed Method to Predict Preterm Birth Using Clinical Data, Standard Maternal Serum Screening, and Cholesterol

PubMed Central

ALLEMAN, Brandon W.; SMITH, Amanda R.; BYERS, Heather M.; BEDELL, Bruce; RYCKMAN, Kelli K.; MURRAY, Jeffrey C.; BOROWSKI, Kristi S.

2013-01-01

Objective To create a predictive model for preterm birth (PTB) from available clinical data and serum analytes. Study Design Serum analytes, routine pregnancy screening plus cholesterol and corresponding health information were linked to birth certificate data for a cohort of 2699 Iowa women with serum sampled in the first and second trimester. Stepwise logistic regression was used to select the best predictive model for PTB. Results Serum screening markers remained significant predictors of PTB even after controlling for maternal characteristics. The best predictive model included maternal characteristics, first trimester total cholesterol (TC), TC change between trimesters and second trimester alpha-fetoprotein and inhibin A. The model showed better discriminatory ability than PTB history alone and performed similarly in subgroups of women without past PTB. Conclusions Using clinical and serum screening data a potentially useful predictor of PTB was constructed. Validation and replication in other populations, and incorporation of other measures that identify PTB risk, like cervical length, can be a step towards identifying additional women who may benefit from new or currently available interventions. PMID:23500456

PTB’s Time and Frequency Activities in 2008 and 2009

DTIC Science & Technology

2009-11-01

techniques (C/A code, P3, carrier phase, PPP). Two-way satellite time and fre- quency transfer ( TWSTFT ) is made routinely with several stations in...and frequency transfer ( TWSTFT ) is routinely per- formed with several European and US stations. PTB provides services to disseminate time and...years 2008 and 2009 are pre- sented. TWSTT AND GPS ACTIVITIES PTB uses TWSTFT and GPS Time Transfer to compare the local time scale UTC (PTB

Is There a Role for Probiotics in the Prevention of Preterm Birth?

PubMed Central

Yang, Siwen; Reid, Gregor; Challis, John R. G.; Kim, Sung O.; Gloor, Gregory B.; Bocking, Alan D.

2015-01-01

Preterm birth (PTB) continues to be a global health challenge. An over-production of inflammatory cytokines and chemokines, as well as an altered maternal vaginal microbiome has been implicated in the pathogenesis of inflammation/infection-associated PTB. Lactobacillus represents the dominant species in the vagina of most healthy pregnant women. The depletion of Lactobacillus in women with bacterial vaginosis (BV) has been associated with an increased risk of PTB. It remains unknown at what point an aberrant vaginal microbiome composition specifically induces the cascade leading to PTB. The ability of oral or vaginal lactobacilli probiotics to reduce BV occurrence and/or dampen inflammation is being considered as a means to prevent PTB. Certain anti-inflammatory properties of lactobacilli suggest potential mechanisms. To date, clinical studies have not been powered with sufficiently high rates of PTB, but overall, there is merit in examining this promising area of clinical science. PMID:25741339

Applying a statistical PTB detection procedure to complement the gold standard.

PubMed

Noor, Norliza Mohd; Yunus, Ashari; Bakar, S A R Abu; Hussin, Amran; Rijal, Omar Mohd

2011-04-01

This paper investigates a novel statistical discrimination procedure to detect PTB when the gold standard requirement is taken into consideration. Archived data were used to establish two groups of patients which are the control and test group. The control group was used to develop the statistical discrimination procedure using four vectors of wavelet coefficients as feature vectors for the detection of pulmonary tuberculosis (PTB), lung cancer (LC), and normal lung (NL). This discrimination procedure was investigated using the test group where the number of sputum positive and sputum negative cases that were correctly classified as PTB cases were noted. The proposed statistical discrimination method is able to detect PTB patients and LC with high true positive fraction. The method is also able to detect PTB patients that are sputum negative and therefore may be used as a complement to the gold standard. Copyright © 2010 Elsevier Ltd. All rights reserved.

Spontaneous preterm birth and single nucleotide gene polymorphisms: a recent update.

PubMed

Sheikh, Ishfaq A; Ahmad, Ejaz; Jamal, Mohammad S; Rehan, Mohd; Assidi, Mourad; Tayubi, Iftikhar A; AlBasri, Samera F; Bajouh, Osama S; Turki, Rola F; Abuzenadah, Adel M; Damanhouri, Ghazi A; Beg, Mohd A; Al-Qahtani, Mohammed

2016-10-17

Preterm birth (PTB), birth at <37 weeks of gestation, is a significant global public health problem. World-wide, about 15 million babies are born preterm each year resulting in more than a million deaths of children. Preterm neonates are more prone to problems and need intensive care hospitalization. Health issues may persist through early adulthood and even be carried on to the next generation. Majority (70 %) of PTBs are spontaneous with about a half without any apparent cause and the other half associated with a number of risk factors. Genetic factors are one of the significant risks for PTB. The focus of this review is on single nucleotide gene polymorphisms (SNPs) that are reported to be associated with PTB. A comprehensive evaluation of studies on SNPs known to confer potential risk of PTB was done by performing a targeted PubMed search for the years 2007-2015 and systematically reviewing all relevant studies. Evaluation of 92 studies identified 119 candidate genes with SNPs that had potential association with PTB. The genes were associated with functions of a wide spectrum of tissue and cell types such as endocrine, tissue remodeling, vascular, metabolic, and immune and inflammatory systems. A number of potential functional candidate gene variants have been reported that predispose women for PTB. Understanding the complex genomic landscape of PTB needs high-throughput genome sequencing methods such as whole-exome sequencing and whole-genome sequencing approaches that will significantly enhance the understanding of PTB. Identification of high risk women, avoidance of possible risk factors, and provision of personalized health care are important to manage PTB.

Dental caries and preterm birth: a systematic review and meta-analysis.

PubMed

Wagle, Madhu; D'Antonio, Francesco; Reierth, Eirik; Basnet, Purusotam; Trovik, Tordis A; Orsini, Giovanna; Manzoli, Lamberto; Acharya, Ganesh

2018-03-02

The primary objective of this systematic review was to evaluate the association between dental caries and preterm birth (PTB). The secondary objective was ascertaining the difference between women with dental caries who experienced PTB and those who did not with regard to decayed, missing and filled teeth (DMFT), and decayed, missing and filled surfaces (DMFS) indices. MEDLINE, Embase, CINAHL and Cochrane databases were searched initially in November 2015 and repeated in December 2016. We included observational cohort and case-control studies. Only studies reporting the risk of PTB in women affected compared with those not affected by dental caries in pregnancy were included. Random-effect meta-analyses were used to compute the summary OR of PTB among women with caries versus women without caries, and the mean difference in either DMFT or DMFS indices between women experiencing PTB and those without PTB. Nine observational studies (4826 pregnancies) were included. Women affected by dental caries during pregnancy did not show a significantly higher risk of PTB (OR: 1.16, 95% CI 0.90 to 1.49, P=0.25, I 2 =35%). Also, the women with PTB did not show significantly higher DMFT or DMFS indices (summary mean differences: 1.56, P=0.10; I 2 =92% and -0.15, P=0.9, I 2 =89%, respectively). Dental caries does not appear to be a substantial risk factor for PTB. NCT01675180; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pregnant women's preferences for and concerns about preterm birth prevention: a cross-sectional survey.

PubMed

Ha, Vanessa; McDonald, Sarah D

2017-01-31

Although there is a call for patient-centred prenatal care, women's preferences for and concerns about preterm birth (PTB) prevention have not been well-studied. Therefore, we conducted a cross-sectional survey to determine women's preferences for PTB prevention and their likelihood of following their healthcare provider's recommendations for PTB prevention, as well as factors associated with these responses. A piloted self-administered questionnaire was completed by pregnant women who could read English. Data were collected about their preferences for and concerns about PTB prevention, and the likelihood of following their healthcare provider's recommendations, using multivariable logistic regression to control for other factors. Three hundred and eleven women at a median of 32-weeks of gestation completed the survey, a response rate of 85.2%. Most women reported that if they were told they were at increased risk for PTB, they preferred not to use PTB prevention (65.8%), of whom almost all (93.4%) reported they preferred close-monitoring and 6.6% preferred neither monitoring nor prevention. A much smaller proportion of women reported that they would not follow their healthcare provider's recommendation for progesterone (10.9%) compared to pessary (28.7%) or cerclage (50.2%). Women who were neither married nor in a common-law relationship were more likely to report that they would not follow recommendations for progesterone (aOR = 5.88 [95% CI: 1.72, 20.00]). Most women (84.5%) reported they would use other sources of information other than their main healthcare provider to learn more about PTB prevention, with the most popular source being the internet. Most women reported that if they were told they were at increased risk of PTB, they preferred close-monitoring over using PTB prevention. Their reported likelihood of not following their healthcare provider's recommendations for PTB prevention varied from 10.9% for progesterone to 50.2% for cerclage. These findings suggest that more education about the risk of PTB, PTB preventions, as well as compliance with progesterone is needed and that the internet would be an important source of information. However as our study was completed by women at a median of 32 weeks of gestation, future surveys targeted at women earlier in their pregnancy are needed.

Protective Effects of Pterostilbene Against Myocardial Ischemia/Reperfusion Injury in Rats.

PubMed

Wu, Miao; Lu, Shijuan; Zhong, Jianghua; Huang, Kang; Zhang, Saidan

2017-04-01

Pterostilbene (PTB) has been suggested to protect against myocardial ischemia/reperfusion (MI/R) injury. Gas6/Axl signaling has been suggested to play an important role in cell survival. However, the interaction between PTB and Gas6/Axl signaling in MI/R remains unclear. This study aims to evaluate the role of Gas6/Axl signaling in the protective effects of PTB against MI/R injury. In experiment 1, the rats were subjected to 30 min of ischemia, followed by 3, 6, and 12 h of reperfusion, respectively. In experiment 2, the rats were administered intraperitoneally with PTB or vehicle and subjected to MI/R injury. The results suggested that the expression of Gas6 and Axl decreased significantly after MI/R injury. PTB treatment conferred a cardioprotective effect with an improved post-ischemic cardiac function, a reduced myocardial infarct size, and decreased lactate dehydrogenase and creatine kinase-MB in the serum, a decreased oxidative stress and inflammation, and a reduced number of apoptotic cardiomyocytes. Moreover, PTB treatment up-regulated the expression of Gas6, Axl, and Bcl-2 and down-regulated Bax expression. Our findings suggest that PTB treatment exerts cardioprotection against MI/R injury via attenuating inflammatory response, oxidative stress, and apoptosis and up-regulating the expression of Gas6 and Axl. The application of PTB may be a new strategy for the treatment of MI/R injury.

Placental villous hypermaturation is associated with idiopathic preterm birth

PubMed Central

Morgan, Terry K.; Tolosa, Jorge E.; Mele, Lisa; Wapner, Ronald J.; Spong, Catherine Y.; Sorokin, Yoram; Dudley, Donald J.; Peaceman, Alan M.; Mercer, Brian M.; Thorp, John M.; O’Sullivan, Mary Jo; Ramin, Susan M.; Rouse, Dwight J.; Sibai, Baha

2014-01-01

Objective Pregnancy complications such as intra-amniotic infection, preeclampsia, and fetal intrauterine growth restriction (IUGR) account for most cases of preterm birth (PTB), but many spontaneous PTB cases do not have a clear etiology. We hypothesize that placental insufficiency may be a potential cause of idiopathic PTB. Methods Secondary analysis of 82 placental samples from women with PTB obtained from a multicenter trial of repeat versus single antenatal corticosteroids. Samples were centrally reviewed by a single placental pathologist masked to clinical outcomes. The histopathologic criterion for infection was the presence of acute chorioamnionitis defined as neutrophils marginating into the chorionic plate. Placental villous hypermaturation (PVH) was defined as a predominance of terminal villi (similar to term placenta) with extensive syncytial knotting. Idiopathic PTB comprised a group without another known etiology such as preeclampsia, IUGR or infection. Results Acute chorioamnionitis was observed in 33/82 (40%) cases. Other known causes of PTB were reported in 18/82 (22%). The remaining 31/82 (38%) were idiopathic. The frequency of PVH in idiopathic PTB (26/31=84%) was similar to cases with IUGR or preeclampsia (16/ 18=89%), but significantly more common than PVH in the group with acute chorioamnionitis (10/33=30%) (p<0.001). Conclusions PVH, which is a histologic marker of relative placental insufficiency, is a common finding in idiopathic PTB. PMID:23130816

Women's prepregnancy underweight as a risk factor for preterm birth: a retrospective study.

PubMed

Girsen, A I; Mayo, J A; Carmichael, S L; Phibbs, C S; Shachar, B Z; Stevenson, D K; Lyell, D J; Shaw, G M; Gould, J B

2016-11-01

To investigate the distribution of known factors for preterm birth (PTB) by severity of maternal underweight; to investigate the risk-adjusted relation between severity of underweight and PTB, and to assess whether the relation differed by gestational age. Retrospective cohort study. State of California, USA. Maternally linked hospital and birth certificate records of 950 356 California deliveries in 2007-2010 were analysed. Singleton live births of women whose prepregnancy body mass index (BMI) was underweight (<18.5 kg/m 2 ) or normal (18.50-24.99 kg/m 2 ) were analysed. Underweight BMI was further categorised as: severe (<16.00), moderate (16.00-16.99) or mild (17.00-18.49). PTB was grouped as 22-27, 28-31, 32-36 or <37 weeks (compared with 37-41 weeks). Adjusted multivariable Poisson regression modeling was used to estimate relative risk for PTB. Risk of PTB. About 72 686 (7.6%) women were underweight. Increasing severity of underweight was associated with increasing percent PTB: 7.8% (n = 4421) in mild, 9.0% (n = 1001) in moderate and 10.2% (475) in severe underweight. The adjusted relative risk of PTB also significantly increased: adjusted relative risk (aRR) = 1.22 (95% CI 1.19-1.26) in mild, aRR = 1.41 (95% CI 1.32-1.50) in moderate and aRR = 1.61 (95% CI 1.47-1.76) in severe underweight. These findings were similar in spontaneous PTB, medically indicated PTB, and the gestational age groupings. Increasing severity of maternal prepregnancy underweight BMI was associated with increasing risk-adjusted PTB at <37 weeks. This increasing risk was of similar magnitude in spontaneous and medically indicated births and in preterm delivery at 28-31 and at 32-36 weeks of gestation. Increasing severity of maternal underweight BMI was associated with increasing risk of preterm birth. © 2016 Royal College of Obstetricians and Gynaecologists.

Label-Free Quantitative Proteomics Identifies Novel Plasma Biomarkers for Distinguishing Pulmonary Tuberculosis and Latent Infection.

PubMed

Sun, Huishan; Pan, Liping; Jia, Hongyan; Zhang, Zhiguo; Gao, Mengqiu; Huang, Mailing; Wang, Jinghui; Sun, Qi; Wei, Rongrong; Du, Boping; Xing, Aiying; Zhang, Zongde

2018-01-01

The lack of effective differential diagnostic methods for active tuberculosis (TB) and latent infection (LTBI) is still an obstacle for TB control. Furthermore, the molecular mechanism behind the progression from LTBI to active TB has been not elucidated. Therefore, we performed label-free quantitative proteomics to identify plasma biomarkers for discriminating pulmonary TB (PTB) from LTBI. A total of 31 overlapping proteins with significant difference in expression level were identified in PTB patients ( n = 15), compared with LTBI individuals ( n = 15) and healthy controls (HCs, n = 15). Eight differentially expressed proteins were verified using western blot analysis, which was 100% consistent with the proteomics results. Statistically significant differences of six proteins were further validated in the PTB group compared with the LTBI and HC groups in the training set ( n = 240), using ELISA. Classification and regression tree (CART) analysis was employed to determine the ideal protein combination for discriminating PTB from LTBI and HC. A diagnostic model consisting of alpha-1-antichymotrypsin (ACT), alpha-1-acid glycoprotein 1 (AGP1), and E-cadherin (CDH1) was established and presented a sensitivity of 81.2% (69/85) and a specificity of 95.2% (80/84) in discriminating PTB from LTBI, and a sensitivity of 81.2% (69/85) and a specificity of 90.1% (64/81) in discriminating PTB from HCs. Additional validation was performed by evaluating the diagnostic model in blind testing set ( n = 113), which yielded a sensitivity of 75.0% (21/28) and specificity of 96.1% (25/26) in PTB vs. LTBI, 75.0% (21/28) and 92.3% (24/26) in PTB vs. HCs, and 75.0% (21/28) and 81.8% (27/33) in PTB vs. lung cancer (LC), respectively. This study obtained the plasma proteomic profiles of different M.TB infection statuses, which contribute to a better understanding of the pathogenesis involved in the transition from latent infection to TB activation and provide new potential diagnostic biomarkers for distinguishing PTB and LTBI.

Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth

PubMed Central

Hong, Xiumei; Hao, Ke; Ji, Hongkai; Peng, Shouneng; Sherwood, Ben; Di Narzo, Antonio; Tsai, Hui-Ju; Liu, Xin; Burd, Irina; Wang, Guoying; Ji, Yuelong; Caruso, Deanna; Mao, Guangyun; Bartell, Tami R.; Zhang, Zhongyang; Pearson, Colleen; Heffner, Linda; Cerda, Sandra; Beaty, Terri H.; Fallin, M. Daniele; Lee-Parritz, Aviva; Zuckerman, Barry; Weeks, Daniel E.; Wang, Xiaobin

2017-01-01

Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such ‘missing heritability' may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide interaction with maternal pre-pregnancy overweight/obesity on PTB risk, with rs11161721 (PG × E=1.8 × 10−8; empirical PG × E=1.2 × 10−8) as the top hit. This interaction is replicated in African-American mothers (PG × E=0.01) from an independent cohort and in meta-analysis (PG × E=3.6 × 10−9), but is not replicated in Caucasians. In adipose tissue, rs11161721 is significantly associated with altered COL24A1 expression. Our findings may provide new insight into the aetiology of PTB and improve our ability to predict and prevent PTB. PMID:28598419

Prevalence and Determinants of Preterm Birth in Tehran, Iran: A Comparison between Logistic Regression and Decision Tree Methods.

PubMed

Amini, Payam; Maroufizadeh, Saman; Samani, Reza Omani; Hamidi, Omid; Sepidarkish, Mahdi

2017-06-01

Preterm birth (PTB) is a leading cause of neonatal death and the second biggest cause of death in children under five years of age. The objective of this study was to determine the prevalence of PTB and its associated factors using logistic regression and decision tree classification methods. This cross-sectional study was conducted on 4,415 pregnant women in Tehran, Iran, from July 6-21, 2015. Data were collected by a researcher-developed questionnaire through interviews with mothers and review of their medical records. To evaluate the accuracy of the logistic regression and decision tree methods, several indices such as sensitivity, specificity, and the area under the curve were used. The PTB rate was 5.5% in this study. The logistic regression outperformed the decision tree for the classification of PTB based on risk factors. Logistic regression showed that multiple pregnancies, mothers with preeclampsia, and those who conceived with assisted reproductive technology had an increased risk for PTB ( p < 0.05). Identifying and training mothers at risk as well as improving prenatal care may reduce the PTB rate. We also recommend that statisticians utilize the logistic regression model for the classification of risk groups for PTB.

The human phosphotyrosine signaling network: Evolution and hotspots of hijacking in cancer

PubMed Central

Li, Lei; Tibiche, Chabane; Fu, Cong; Kaneko, Tomonori; Moran, Michael F.; Schiller, Martin R.; Li, Shawn Shun-Cheng; Wang, Edwin

2012-01-01

Phosphotyrosine (pTyr) signaling, which plays a central role in cell–cell and cell–environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 representative eukaryotic species and assigned their evolutionary origins. We found that human TK circuits for intracellular pTyr signaling originated largely from primitive organisms, whereas the inter- or extracellular signaling circuits experienced significant expansion in the bilaterian lineage through the “back-wiring” of newly evolved kinases to primitive substrates and SH2/PTB domains. Conversely, the TK circuits that are involved in tissue-specific signaling evolved mainly in vertebrates by the back-wiring of vertebrate substrates to primitive kinases and SH2/PTB domains. Importantly, we found that cancer signaling preferentially employs the pTyr sites, which are linked to more TK circuits. Our work provides insights into the evolutionary paths of the human pTyr signaling circuits and suggests the use of a network approach for cancer intervention through the targeting of key pTyr sites and their associated signaling hubs in the network. PMID:22194470

Pseudotachylitic breccia in mafic and felsic rocks

NASA Astrophysics Data System (ADS)

Kovaleva, Elizaveta; Huber, Matthew S.

2017-04-01

Impact-produced pseudotachylitic breccia (PTB) is abundant in the core of the Vredefort impact structure and was found in many pre-impact lithologies (e.g., Reimold and Colliston, 1994; Gibson et al., 1997). The mechanisms involved in the process of forming this rock remain highly debated, and various authors have discussed many possible models. We investigate PTB from two different rock types: meta-granite and meta-gabbro and test how lithology controls the development of PTB. We also report on clast transport between different lithologies. In the core of the Vredefort impact structure, meta-granite and meta-gabbro are observed in contact with each other, with an extensive set of PTB veins cutting through both lithologies. Microstructural analyses of the PTB veins in thin sections reveals differences between PTBs in meta-granite and meta-gabbro. In granitic samples, PTB often develops along contacts of material with different physical properties, such as a contact with a migmatite or pegmatite vein. Nucleation sites of PTB have features consistent with ductile deformation and shearing, such as sigmoudal-shaped clasts and dragged edges of the veins. Preferential melting of mafic and hydrous minerals takes place (e.g., Reimold and Colliston, 1994; Gibson et al., 2002). Refractory phases remain in the melt as clasts and form reaction rims. In contrast, PTB in meta-gabbro develop in zones with brittle deformation, and do not exploit existing physical contacts. Cataclastic zones develop along the faults and progressively produce ultracataclasites and melt. Thus, PTB veins in meta-gabbro contain fewer clasts. Clasts usually represent multi-phase fragments of host rock and not specific phases. Such fragments often originate from the material trapped between two parallel or horse-tail faults. The lithological control on the development of PTB does not imply that PTB develops independently in different lithologies. We have observed granitic clasts within PTB veins in meta-gabbro, demonstrating clast transport between lithologies. PT melt in meta-gabbro has a two-phase structure: a phase free of granitic clasts, and a phase that contains granitic clasts. This also indicates that melt in both rock types was mobile during the same period of time, and that physical mixing and chemical exchange occurred between the two melts. Thus, PTB cuts across the contact between granite and gabbro, and is not restricted by the contact (e.g., Reimold and Colliston, 1994). These differences in nucleation and propagation of PTB based on rock type must be considered when discussing the formation mechanisms of impact-generated PTB. References: Gibson R.L., Reimold W.U., Ashley A.J., Koeberl C. (2002) Metamorphism of the Moon: A terrestrial analogue in the Vredefort dome, South Africa? Geology 30:475-478. Gibson R.L., Reimold W.U., Wallmach T. (1997) Origin of pseudotachylite in the lower Witwatersrand Supergroup, Vredefort Dome (South Africa): constraints from metamorphic studies. Tectonophysics 283:241-262. Reimold W.U., Colliston W.P. (1994) Pseudotachylites of the Vredefort Dome and the surrounding Witwatersrand Basin, South Africa. Geological Society of America Special Papers 293:177-196.

Data Modulation Test Equipment for Microcavity Transistor Lasers

DTIC Science & Technology

2014-09-04

Eye at 56 Gb/s With the Agilent 86107A-040 Precision Time Base module ( PTB ) installed, we were able to see an improvement in the jitter...modulation rate at 40 Gb/s (a) without PTB and (b) with PTB . A DC component of about -354.8mV is associated with the modulation data signal. As we can see...from the eye diagrams above, the fall time and rise time transitions are much cleaner, less jitter, with the installation of the PTB . The jitter

Nonesterified Fatty Acids and Spontaneous Preterm Birth: A Factor Analysis for Identification of Risk Patterns

PubMed Central

Catov, Janet M.; Bertolet, Marnie; Chen, Yi-Fan; Evans, Rhobert W.; Hubel, Carl A.

2014-01-01

We considered that accumulation of nonesterified (free) fatty acids (NEFAs) in the first trimester of pregnancy would mark women at excess risk of spontaneous preterm birth (sPTB) and examined the interplay between NEFAs, lipids, and other markers to explore pathways to sPTB. In a case-control study nested in the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997–2001), we assayed NEFA levels in nonfasting serum collected at a mean gestational week of 9.4 (range, 4–20 weeks) in 115 women with sPTB (<37 weeks) and 222 women with births occurring at ≥37 weeks. C-reactive protein, total cholesterol, low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, triglycerides, and uric acid were also measured. Polytomous logistic regression models were used to evaluate tertiles of NEFA levels and sPTB at <34 weeks and 34–36 weeks; factor analysis was used to characterize patterns of biomarkers. Women with NEFA levels in the highest tertile versus the lowest were 2.02 (95% confidence interval: 1.13, 3.48) times more likely to have sPTB, after adjustment for covariates. Risk of sPTB before 34 weeks was particularly high among women with high NEFA levels (odds ratio = 3.73, 95% confidence interval: 1.33, 10.44). Six biomarker patterns were identified, and 2 were associated with sPTB: 1) increasing NEFA and HDL cholesterol levels and 2) family history of gestational hypertension. NEFA levels early in pregnancy were independently associated with sPTB, particularly before 34 weeks. We also detected a novel risk pattern suggesting that NEFAs together with HDL cholesterol may be related to sPTB. PMID:24714724

Nonesterified fatty acids and spontaneous preterm birth: a factor analysis for identification of risk patterns.

PubMed

Catov, Janet M; Bertolet, Marnie; Chen, Yi-Fan; Evans, Rhobert W; Hubel, Carl A

2014-05-15

We considered that accumulation of nonesterified (free) fatty acids (NEFAs) in the first trimester of pregnancy would mark women at excess risk of spontaneous preterm birth (sPTB) and examined the interplay between NEFAs, lipids, and other markers to explore pathways to sPTB. In a case-control study nested in the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997-2001), we assayed NEFA levels in nonfasting serum collected at a mean gestational week of 9.4 (range, 4-20 weeks) in 115 women with sPTB (<37 weeks) and 222 women with births occurring at ≥37 weeks. C-reactive protein, total cholesterol, low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, triglycerides, and uric acid were also measured. Polytomous logistic regression models were used to evaluate tertiles of NEFA levels and sPTB at <34 weeks and 34-36 weeks; factor analysis was used to characterize patterns of biomarkers. Women with NEFA levels in the highest tertile versus the lowest were 2.02 (95% confidence interval: 1.13, 3.48) times more likely to have sPTB, after adjustment for covariates. Risk of sPTB before 34 weeks was particularly high among women with high NEFA levels (odds ratio = 3.73, 95% confidence interval: 1.33, 10.44). Six biomarker patterns were identified, and 2 were associated with sPTB: 1) increasing NEFA and HDL cholesterol levels and 2) family history of gestational hypertension. NEFA levels early in pregnancy were independently associated with sPTB, particularly before 34 weeks. We also detected a novel risk pattern suggesting that NEFAs together with HDL cholesterol may be related to sPTB.

Role of Perceived Stress on the Occurrence of Preterm Labor and Preterm Birth among Urban Women

PubMed Central

Seravalli, Laura; Patterson, Freda; Nelson, Deborah B.

2013-01-01

Introduction This study examined whether prenatal perceived stress levels during pregnancy were associated with preterm labor (PTL) or preterm birth (PTB). Methods Perceived stress levels were measured at 16 weeks gestation or less and between 20 and 24 weeks gestation in a sample of 1,069 low-income pregnant women attending Temple University prenatal care clinics. Scores were averaged to create a single measure of prenatal stress. PTB was defined as the occurrence of a spontaneous birth prior to 37 weeks gestation. PTL was defined as the occurrence of regular contractions between 20 and 37 weeks of pregnancy that were associated with changes in the cervix. Results Independent of potential confounding factors, prenatal perceived stress was not associated with PTL (OR 1.10; 95% CI 0.69-1.78, P = .66); however, prenatal stress trended toward an association with PTB (OR 1.49; 95% CI: 1.00-2.23, P =.05). The strongest predictor of preterm labor was a history of preterm labor in a prior pregnancy. Women with a history of PTL were two times more likely to experience PTL in the current pregnancy than women who did not have a PTL history (OR 2.16; 95% CI 1.05-4.41, P =.04). Historical risk factors of PTB, such as African American race, a history of abortion or a history of PTB were not related to PTL. The strongest predictor of PTB was having a history of PTB in a prior pregnancy (OR 2.55; 95% CI 1.54-4.24, P <.001). Discussion Prenatal perceived stress levels may be a risk factor for PTB independent of PTL; however, prenatal stress was not associated with PTL. Risk factors for PTL may be different from those of PTB. PMID:24890400

Localization of a major susceptibility locus influencing preterm birth

PubMed Central

Chittoor, G.; Farook, V.S.; Puppala, S.; Fowler, S.P.; Schneider, J.; Dyer, T.D.; Cole, S.A.; Lynch, J.L.; Curran, J.E.; Almasy, L.; MacCluer, J.W.; Comuzzie, A.G.; Hale, D.E.; Ramamurthy, R.S.; Dudley, D.J.; Moses, E.K.; Arya, R.; Lehman, D.M.; Jenkinson, C.P.; Bradshaw, B.S.; DeFronzo, R.A.; Blangero, J.; Duggirala, R.

2013-01-01

Preterm birth (PTB) is a complex trait, but little is known regarding its major genetic determinants. The objective of this study is to localize genes that influence susceptibility to PTB in Mexican Americans (MAs), a minority population in the USA, using predominantly microfilmed birth certificate-based data obtained from the San Antonio Family Birth Weight Study. Only 1302 singleton births from 288 families with information on PTB and significant covariates were considered for genetic analysis. PTB is defined as a childbirth that occurs at <37 completed weeks of gestation, and the prevalence of PTB in this sample was 6.4%. An ∼10 cM genetic map was used to conduct a genome-wide linkage analysis using the program SOLAR. The heritability of PTB was high (h2 ± SE: 0.75 ± 0.20) and significant (P = 4.5 × 10−5), after adjusting for the significant effects of birthweight and birth order. We found significant evidence for linkage of PTB (LOD = 3.6; nominal P = 2.3 × 10−5; empirical P = 1.0 × 10−5) on chromosome 18q between markers D18S1364 and D18S541. Several other chromosomal regions (2q, 9p, 16q and 20q) were also potentially linked with PTB. A strong positional candidate gene in the 18q linked region is SERPINB2 or PAI-2, a member of the plasminogen activator system that is associated with various reproductive processes. In conclusion, to our knowledge, perhaps for the first time in MAs or US populations, we have localized a major susceptibility locus for PTB on chromosome 18q21.33-q23. PMID:23689979

Association between preterm birth and its subtypes and maternal sociodemographic characteristics during the post-transitional phase in a developing country with a very high human development index.

PubMed

Araya, B M; Díaz, M; Paredes, D; Ortiz, J

2017-06-01

Chile is a post-transitional country evolving towards a stationary population pyramid, which may be associated with increasing preterm birth (PTB) rates. This study aimed to compare maternal sociodemographic characteristics between the start of the post-transition phase (1994) and an established stage (2013) and to evaluate associations between these characteristics and PTB. An observational analytic design was conducted using national birth records (n = 4,956,311). Variables analysed in the 20 birth cohorts from 1994 to 2013 were: length of gestation (preterm <37 weeks) subdivided by gestational age (extreme, moderate/severe and late); maternal age (≤19, 20-35 and >35 years); education level (<8, 8-12 and >12 years of education); employment; marital status; area of residence; and type of birth (singleton, twins, and triplets or higher order). The prevalence of PTB was expressed as a percentage, and associations between PTB and predictor variables were analysed using logistic regression models. Education level, age >35 years, maternal employment, unmarried status, twin delivery and urban residency rates increased between 1994 and 2013. According to the adjusted models, age >35 years and delivery of more than two foetuses were risk factors for all PTB subtypes. Maternal employment was a risk factor for moderate/severe, late and total PTB, and a low level of education was a risk factor for late and total PTB. On the other hand, age ≤19 years was protective against all PTB subtypes. All maternal characteristics changed between 1994 and 2013. Furthermore, the prevalence of PTB increased for all predictor variables studied over this period. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Genetic Influences on Preterm Birth in Argentina

PubMed Central

Mann, Paul C.; Cooper, Margaret E.; Ryckman, Kelli K.; Comas, Belén; Gili, Juan; Crumley, Suzanne; Bream, Elise N.A.; Byers, Heather M.; Piester, Travis; Schaefer, Amanda; Christine, Paul J.; Lawrence, Amy; Schaa, Kendra L.; Kelsey, Keegan J.P.; Berends, Susan K.; Gadow, Enrique; Cosentino, Viviana; Castilla, Eduardo E.; Camelo, Jorge López; Saleme, Cesar; Day, Lori J.; England, Sarah K.; Marazita, Mary L.; Dagle, John M.; Murray, Jeffrey C.

2013-01-01

Objective To investigate genetic etiologies of preterm birth (PTB) in Argentina through evaluation of single-nucleotide polymorphisms (SNP) in candidate genes and population genetic admixture. Study Design Genotyping was performed in 389 families. Maternal, paternal, and fetal effects were studied separately. Mitochondrial DNA (mtDNA) was sequenced in 50 males and 50 females. Y-chromosome anthropological markers were evaluated in 50 males. Results Fetal association with PTB was found in the progesterone receptor (PGR, rs1942836; p= 0.004). Maternal association with PTB was found in small conductance calcium activated potassium channel isoform 3 (KCNN3, rs883319; p= 0.01). Gestational age associated with PTB in PGR rs1942836 at 32 –36 weeks (p= 0.0004). MtDNA sequencing determined 88 individuals had Amerindian consistent haplogroups. Two individuals had Amerindian Y-chromosome consistent haplotypes. Conclusions This study replicates single locus fetal associations with PTB in PGR, maternal association in KCNN3, and demonstrates possible effects for divergent racial admixture on PTB. PMID:23018797

Association of Pulmonary Tuberculosis and HIV in the Mexican Institute of Social Security, 2006-2014.

PubMed

Cabrera-Gaytán, David Alejandro; Niebla-Fuentes, María Del Rosario; Padilla-Velázquez, Rosario; Valle-Alvarado, Gabriel; Arriaga-Nieto, Lumumba; Rojas-Mendoza, Teresita; Rosado-Quiab, Ulises; Grajales-Muñiz, Concepción; Vallejos-Parás, Alfonso

2016-01-01

Tuberculosis and HIV remain a public health problem in developed countries. The objective of this study was to analyze the incidence trends of pulmonary TB and HIV comorbidity and treatment outcomes according to HIV during the period 2006 to 2014 in the Mexican Institute of Social Security. Analyzed data from this registry including pulmonary tuberculosis patients aged 15 years and older who had been diagnosed during the years 2006 to 2014 in the Mexican Institute of Social Security. The outcomes that we use were incidents rate, failure to treatment and death. Regression models were used to quantify associations between pulmonary tuberculosis and HIV mortality. During the study period, 31,352 patients were registered with pulmonary tuberculosis. The incidence rate observed during 2014 was 11.6 case of PTB per 100,000. The incidence rate for PTB and HIV was 0.345 per 100,000. The PTB incidence rate decreased by 0.07%, differences found in the PTB incidence rate by sex since in women decreased by 5.52% and in man increase by 3.62%. The pulmonary TB with HIV incidence rate decreased by 16.3% during the study period (In women increase 4.81% and in man decrease 21.6%). Analysis of PTB associated with HIV by age groups revealed that the highest incidence rates were observed for the 30 to 44 years old group. Meanwhile, the highest incidence rates of PTB without HIV occurred among the 60 and more years old individuals. We did not find statistically significant differences between treatment failure and PTB patients with HIV and without HIV. The treatment failure was associated with sex and the region of the patient. We found a strong association between HIV and the probability of dying during treatment. Our data suggested that patients suffering from both conditions (PTB and HIV) have no difference in the probability of failure of treatment contrary to other reports. Hypotheses to this is adherence to tuberculosis treatment with people living with HIV/AIDS, detection of PTB in patients suffering from HIV/AIDS or PTB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on antiretroviral treatment. We have found that PTB and HIV increases the probability of dying during treatment compared to the cases of PTB without HIV, consistent with published other study HIV increases the mortality rates associated with PTB. No association between pulmonary tuberculosis with HIV and treatment failure was observed, but pulmonary tuberculosis and HIV increases the probability of dying during treatment compared to the pulmonary tuberculosis cases without HIV.

Prophylactic antibiotics for the prevention of preterm birth in women at risk: a meta-analysis.

PubMed

Simcox, Rachael; Sin, Wing-To A; Seed, Paul T; Briley, Annette; Shennan, Andrew H

2007-10-01

Preterm birth (PTB) is the major determinant of perinatal morbidity and mortality. Infection is implicated in a large proportion of preterm deliveries, but there is no consensus regarding the efficacy of antibiotic prophylaxis for women at risk. To determine whether antibiotic treatment reduces the risk of preterm delivery in asymptomatic pregnant women at risk of PTB. Relevant publications were identified via electronic searches of MEDLINE (1966 to August 2005), The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Central Register of Controlled Trials (the Cochrane Library, Issue 3, 2005) and PubMed using multiple search terms related to PTB and antibiotics. Publications were limited to randomised controlled trials comparing antibiotics with placebo given to asymptomatic non-labouring women. A random effect model was used, and combined risk ratios calculated for the various risk groups. Associations between treatment effect and the rate of PTB were analysed by meta-regression. Seventeen trials were included, 12 identifying women at risk by abnormal vaginal flora, three on women at high risk from a previous PTB and two recruiting women based on positive fetal fibronectin status. There was no significant association between antibiotic treatment and reduction in PTB irrespective of criteria used to assess risk, the antimicrobial agent administered, or gestational age at time of treatment (overall combined random effect for delivery at less than 37 weeks RR 1.03 (95% CI 0.86-1.24)). Treating women at risk of PTB with antibiotics does not reduce the risk of subsequent PTB.

Residential proximity to gasoline service stations and preterm birth.

PubMed

Huppé, Vicky; Kestens, Yan; Auger, Nathalie; Daniel, Mark; Smargiassi, Audrey

2013-10-01

Preterm birth (PTB) is a growing public health problem potentially associated with ambient air pollution. Gasoline service stations can emit atmospheric pollutants, including volatile organic compounds potentially implicated in PTB. The objective of this study was to evaluate the relationship between residential proximity to gasoline service stations and PTB. Singleton live births on the Island of Montreal from 1994 to 2006 were obtained (n=267,478). Gasoline service station locations, presence of heavy-traffic roads, and neighborhood socioeconomic status (SES) were determined using a geographic information system. Multivariable logistic regression was used to analyze the association between PTB and residential proximity to gasoline service stations (50, 100, 150, 200, 250, and 500 m), accounting for maternal covariates, neighborhood SES, and heavy-traffic roads. For all distance categories beyond 50 m, presence of service stations was associated with a greater odds of PTB. Associations were robust to adjustment for maternal covariates for distance categories of 150 and 200 m but were nullified when adjusting for neighborhood SES. In analyses accounting for the number of service stations, the likelihood of PTB within 250 m was statistically significant in unadjusted models. Associations were, however, nullified in models accounting for maternal covariates or neighborhood SES. Our results suggest that there is no clear association between residential proximity to gasoline service stations in Montreal and PTB. Given the correlation between proximity of gasoline service stations and SES, it is difficult to delineate the role of these factors in PTB.

Impact of Community-Based DOT on Tuberculosis Treatment Outcomes: A Systematic Review and Meta-Analysis

PubMed Central

Zhang, HaiYang; Ehiri, John; Yang, Huan; Tang, Shenglan; Li, Ying

2016-01-01

Background Poor adherence to tuberculosis (TB) treatment can lead to prolonged infectivity and poor treatment outcomes. Directly observed treatment (DOT) seeks to improve adherence to TB treatment by observing patients while they take their anti-TB medication. Although community-based DOT (CB-DOT) programs have been widely studied and promoted, their effectiveness has been inconsistent. The aim of this study was to critical appraise and summarize evidence of the effects of CB-DOT on TB treatment outcomes. Methods Studies published up to the end of February 2015 were identified from three major international literature databases: Medline/PubMed, EBSCO, and EMBASE. Unpublished data from the grey literature were identified through Google and Google Scholar searches. Results Seventeen studies involving 12,839 pulmonary TB patients (PTB) in eight randomized controlled trials (RCTs) and nine cohort studies from 12 countries met the criteria for inclusion in this review and 14 studies were included in meta-analysis. Compared with clinic-based DOT, pooled results of RCTs for all PTB cases (including smear-negative or -positive, new or retreated TB cases) and smear-positive PTB cases indicated that CB-DOT promoted successful treatment [pooled RRs (95%CIs): 1.11 (1.02–1.19) for all PTB cases and 1.11 (1.02–1.19) for smear-positive PTB cases], and completed treatment [pooled RRs (95%CIs): 1.74(1.05, 2.90) for all PTB cases and 2.22(1.16, 4.23) for smear-positive PTB cases], reduced death [pooled RRs (95%CIs): 0.44 (0.26–0.72) for all PTB cases and 0.39 (0.23–0.66) for smear-positive PTB cases], and transfer out [pooled RRs (95%CIs): 0.37 (0.23–0.61) for all PTB cases and 0.42 (0.25–0.70) for smear-positive PTB cases]. Pooled results of all studies (RCTs and cohort studies) with all PTB cases demonstrated that CB-DOT promoted successful treatment [pooled RR (95%CI): 1.13 (1.03–1.24)] and curative treatment [pooled RR (95%CI): 1.24 (1.04–1.48)] compared with self-administered treatment. Conclusions CB-DOT did improved TB treatment outcomes according to the pooled results of included studies in this review. Studies on strategies for implementation of patient-centered and community-centered CB-DOT deserve further attention. PMID:26849656

Umbilical cord blood and maternal visfatin (PBEF/NAMPT) concentrations in preterm birth with and without preterm premature rupture of membranes.

PubMed

Pavlová, Tereza; Zlámal, Filip; Šplíchal, Zbyněk; Tomandl, Josef; Hodická, Zuzana; Ventruba, Pavel; Bienertová-Vašků, Julie

2018-07-01

The aim of the study is to investigate differences in visfatin concentrations between mothers with term and preterm birth (PTB) and between mothers who delivered within seven days and after more than seven days following admission for PTB/preterm premature rupture of membranes (PPROMs). Maternal peripheral blood and cord blood were collected from 56 mothers with PTB (31 with PPROM) and 71 mothers with term delivery (three with PPROM). Maternal visfatin concentration was significantly higher for given gestational age in PTBs compared to term deliveries (p = .021) and also in mothers who delivered within seven days after admission for PTB or PPROM, compared to those who delivered after more than seven days (p = .027; p = .039). Cord blood visfatin concentration was found to be decreased in preterm compared to term infants (p = .007). Visfatin in both maternal and fetal circulation may play an important role in the pathogenesis of PTB/PPROM and could be used to distinguish between women who will deliver in a short period of time after clinical presentation of PTB/PPROM and those who deliver later. Nevertheless, additional research is necessary in order to identify its direct involvement in PTB/PPROM.

The origin of high PCE in PTB7 based photovoltaics: proper charge neutrality level and free energy of charge separation at PTB7/PC71BM interface

PubMed Central

Park, Soohyung; Jeong, Junkyeong; Hyun, Gyeongho; Kim, Minju; Lee, Hyunbok; Yi, Yeonjin

2016-01-01

The energy level alignments at donor/acceptor interfaces in organic photovoltaics (OPVs) play a decisive role in device performance. However, little is known about the interfacial energetics in polymer OPVs due to technical issues of the solution process. Here, the frontier ortbial line-ups at the donor/acceptor interface in high performance polymer OPVs, PTB7/PC71BM, were investigated using in situ UPS, XPS and IPES. The evolution of energy levels during PTB7/PC71BM interface formation was investigated using vacuum electrospray deposition, and was compared with that of P3HT/PC61BM. At the PTB7/PC71BM interface, the interface dipole and the band bending were absent due to their identical charge neutrality levels. In contrast, a large interfacial dipole was observed at the P3HT/PC61BM interface. The measured photovoltaic energy gap (EPVG) was 1.10 eV for PTB7/PC71BM and 0.90 eV for P3HT/PC61BM. This difference in the EPVG leads to a larger open-circuit voltage of PTB7/PC71BM than that of P3HT/PC61BM. PMID:27734957

The origin of high PCE in PTB7 based photovoltaics: proper charge neutrality level and free energy of charge separation at PTB7/PC71BM interface.

PubMed

Park, Soohyung; Jeong, Junkyeong; Hyun, Gyeongho; Kim, Minju; Lee, Hyunbok; Yi, Yeonjin

2016-10-13

The energy level alignments at donor/acceptor interfaces in organic photovoltaics (OPVs) play a decisive role in device performance. However, little is known about the interfacial energetics in polymer OPVs due to technical issues of the solution process. Here, the frontier ortbial line-ups at the donor/acceptor interface in high performance polymer OPVs, PTB7/PC 71 BM, were investigated using in situ UPS, XPS and IPES. The evolution of energy levels during PTB7/PC 71 BM interface formation was investigated using vacuum electrospray deposition, and was compared with that of P3HT/PC 61 BM. At the PTB7/PC 71 BM interface, the interface dipole and the band bending were absent due to their identical charge neutrality levels. In contrast, a large interfacial dipole was observed at the P3HT/PC 61 BM interface. The measured photovoltaic energy gap (E PVG ) was 1.10 eV for PTB7/PC 71 BM and 0.90 eV for P3HT/PC 61 BM. This difference in the E PVG leads to a larger open-circuit voltage of PTB7/PC 71 BM than that of P3HT/PC 61 BM.

Identification of new diagnostic biomarkers for Mycobacterium tuberculosis and the potential application in the serodiagnosis of human tuberculosis.

PubMed

Ren, Ningning; JinLi, Jingfang; Chen, Yingyu; Zhou, Xia; Wang, Jieru; Ge, Pan; Khan, Farhan Anwar; Zhang, Li; Hu, Changmin; Robertson, Ian D; Chen, Huanchun; Guo, Aizhen

2018-06-27

Mycobacterium tuberculosis (M. tuberculosis) regions of difference (RD) encode proteins which are potentially useful as diagnostic reagents for tuberculosis (TB). In this study, 75 genes from M. tuberculosis RD1-RD16 were successfully cloned from which 68 proteins were expressed and purified. Three serum pools from patients with pulmonary TB (PTB), extra-pulmonary tuberculosis (EPTB) and healthy controls (HC) were used to preliminarily screen individual RD proteins. The OD 630 ratio of the PTB or EPTB to the HC group ≥ 2-fold was positive. As a result, 29 proteins were obtained. The serological response to the identified antigens was further verified using 58 PTB samples with 38 sera from smear-positive PTB (PTB-SP) patients and 20 sera from smear-negative PTB (PTB-SN) patients, 16 EPTB samples, 42 latent M. tuberculosis infection samples and 40 HCs by indirect ELISA. With respect to the PTB diagnosis, receiver operating characteristic analysis showed that Rv0222 [area under the curve (AUC), 0.8129; 95% confidence interval (CI), 0.7280-0.8979] and Rv3403c (AUC, 0.8537; 95% CI, 0.7779-0.9294) performed better than ESAT6/CFP10 (AUC, 0.7435; 95% CI, 0.6465-0.8406). Rv0222 and Rv3403c demonstrated the highest diagnostic ability in the PTB-SP group (sensitivity, 86.8%; specificity, 80%), while Rv3403c demonstrated the highest diagnostic ability in the PTB-SN group (sensitivity, 70%; specificity, 80%). With respect to the EPTB diagnosis, Rv0222 exhibited the highest diagnostic value (AUC, 0.7523; sensitivity, 68.8%; specificity, 87.5%). In addition, the combination of Rv0222 and Rv3403c improved the test for PTB-SN. These results indicate that Rv0222 and Rv3403c would be potential diagnostic biomarkers for active TB serodiagnosis. Mouse experiments demonstrated that Rv0222 and Rv3403c elicited specific cellular and humoral responses which were characterized by production of IFN-γ, IgG1, and IgG2a, but a higher level of IgG1 than IgG2a. © 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Comparison of antibody responses against Mycobacterium tuberculosis antigen Rv0679c in tuberculosis patients from the endemic and non-endemic regions of the Beijing genotype: a case control study.

PubMed

Zhao, Jingge; Matsuba, Takashi; Zhang, Xiaoyan; Leano, Susan; Nakajima, Chie; Chagan-Yasutan, Haorile; Telan, Elizabeth Freda; Suzuki, Yasuhiko; Hattori, Toshio

2017-05-15

Strains of the Beijing genotype of Mycobacterium tuberculosis (MTB) are reportedly associated with the virulence of tuberculosis (TB) infection, unfavorable outcomes of anti-TB treatment, and the global TB pandemic. Rv0679c, a hypothetical membrane protein related to host cell invasion, has a Beijing genotype-specific mutation at residue 142 (Asn142Lys). Antigenicity differences between Rv0679c-Asn142 (N-type) and Rv0679c-Lys142 (K-type) have been previously observed in mice antigen-antibody responses. However, the immune response to Rv0679c in humans remains unknown. Therefore, we aimed to investigate the anti-Rv0679c immune response in TB patients from the endemic and non-endemic regions of the Beijing MTB genotype. We analyzed the Rv0679c-specific antibody responses in 84 subjects from the endemic region of the Beijing genotype MTB in China, including 45 pulmonary TB patients (C-PTB) and 39 healthy controls (C-HC), and 81 subjects from the Philippines (the endemic region of the non-Beijing genotype), including 51 pulmonary TB patients (P-PTB) and 30 healthy controls (P-HC). Anti-tuberculous-glycolipid (TBGL) antigen was used as the control antibody. TBGL IgG titers were higher in both C-PTB and P-PTB than those in their corresponding HC (C-PTB median 4.2, P-PTB median 11.2; C-PTB vs. P-PTB, p > 0.05), suggesting immune response comparability in PTB from two different countries. C-PTB showed a higher response compared to C-HC for anti-K-type IgG (53.3%) than anti-N-type IgG (6.67%); this response was not observed in P-PTB (both N-type and K-type 9.80%). Dimorphic antigen Rv0679c was found to be associated with distinct immune response patterns, indicating the role of Beijing/non-Beijing genotype of MTB in stimulating specific responses in TB patients from the endemic region of Beijing MTB. Meanwhile, reactions to Rv0679c in patients and HC from non-endemic regions of the Beijing MTB may be caused by the response to the common epitope of Rv0679c N/K-type.

Changes in respiratory function impairment following the treatment of severe pulmonary tuberculosis - limitations for the underlying COPD detection.

PubMed

Radovic, Milan; Ristic, Lidija; Ciric, Zorica; Dinic-Radovic, Violeta; Stankovic, Ivana; Pejcic, Tatjana; Rancic, Milan; Bogdanovic, Dragan

2016-01-01

During the treatment phase of active pulmonary tuberculosis (PTB), respiratory function impairment is usually restrictive. This may become obstructive, as a PTB-associated airflow obstruction (AFO) or as a later manifestation of underlying COPD. The aim of the study was to examine the potential causes and risks for AFO development in PTB by exploring the aspects of spirometry limitations and clinical implications for the underlying COPD detection, taking into account various confounding factors. Prospective, nest case-control study on 40 new cases of PTB with initial restrictive respiratory function impairment, diagnosed and treated according to the directly observed treatment short course (DOTS) strategy. From all observed patients, 37.5% of them developed AFO upon the completion of PTB treatment, with significantly increased average of forced vital capacity (%) (P<0.01). Their changes in forced expiratory volume in the first second (%) during the PTB treatment were strongly associated with the air pollution exposure in living (0.474%-20.971% for 95% confidence interval [CI]; P=0.041) and working environments (3.928%-20.379% for 95% CI; P=0.005), initial radiological extent of PTB lesions (0.018%-0.700% for 95% CI; P=0.047), leukocyte count (0.020%-1.328% for 95% CI; P=0.043), and C-reactive protein serum level (0.046%-0.205% for 95% CI; P=0.003) compared to the other patients. The multivariate logistic regression analysis model shows initial radiological extent of pulmonary tuberculosis lesions (OR 1.01-1.05 for 95% CI; P=0.02) and sputum conversion rate on culture (OR 1.02-1.68 for 95% CI; P=0.04) as the most significant predictors for the risk of AFO development. AFO upon PTB treatment is a common manifestation of underlying COPD, which mostly occurs later, during the reparative processes in active PTB, even in the absence of major risk factors, such as cigarette smoking and biomass fuel dust exposure. Initial spirometry testing in patients with active PTB is not a sufficient and accurate approach in the detection of underlying COPD, which may lead to their further potential health deterioration.

Preterm birth: the role of knowledge transfer and exchange.

PubMed

Horvath, Hacsi; Brindis, Claire D; Reyes, E Michael; Yamey, Gavin; Franck, Linda

2017-09-06

Preterm birth (PTB) is the leading cause of death in children under age five. Healthcare policy and other decision-making relevant to PTB may rely on obsolete, incomplete or inapplicable research evidence, leading to worsened outcomes. Appropriate knowledge transfer and exchange (KTE) strategies are an important component of efforts to reduce the global PTB burden. We sought to develop a 'landscape' analysis of KTE strategies currently used in PTB and related contexts, and to make recommendations for optimising programmatic implementation and for future research. In the University of California, San Francisco's Preterm Birth Initiative, we convened a multidisciplinary working group and examined KTE frameworks. After selecting a widely-used, adaptable, theoretically-strong framework we reviewed the literature to identify evidence-based KTE strategies. We analysed KTE approaches focusing on key PTB stakeholders (individuals, families and communities, healthcare providers and policymakers). Guided by the framework, we articulated KTE approaches that would likely improve PTB outcomes. We further applied the KTE framework in developing recommendations. We selected the Linking Research to Action framework. Searches identified 19 systematic reviews, including two 'reviews of reviews'. Twelve reviews provided evidence for KTE strategies in the context of maternal, neonatal and child health, though not PTB specifically; seven reviews provided 'cross-cutting' evidence that could likely be generalised to PTB contexts. For individuals, families and communities, potentially effective KTE strategies include community-based approaches, 'decision aids', regular discussions with providers and other strategies. For providers, KTE outcomes may be improved through local opinion leaders, electronic reminders, multifaceted strategies and other approaches. Policy decisions relevant to PTB may best be informed through the use of evidence briefs, deliberative dialogues, the SUPPORT tools for evidence-informed policymaking and other strategies. Our recommendations for research addressed knowledge gaps in regard to partner engagement, applicability and context, implementation strategy research, monitoring and evaluation, and infrastructure for sustainable KTE efforts. Evidence-based KTE, using strategies appropriate to each stakeholder group, is essential to any effort to improve health at the population level. PTB stakeholders should be fully engaged in KTE and programme planning from its earliest stages, and ideally before planning begins.

Subgroup identification of early preterm birth (ePTB): informing a future prospective enrichment clinical trial design.

PubMed

Zhang, Chuanwu; Garrard, Lili; Keighley, John; Carlson, Susan; Gajewski, Byron

2017-01-10

Despite the widely recognized association between the severity of early preterm birth (ePTB) and its related severe diseases, little is known about the potential risk factors of ePTB and the sub-population with high risk of ePTB. Moreover, motivated by a future confirmatory clinical trial to identify whether supplementing pregnant women with docosahexaenoic acid (DHA) has a different effect on the risk subgroup population or not in terms of ePTB prevalence, this study aims to identify potential risk subgroups and risk factors for ePTB, defined as babies born less than 34 weeks of gestation. The analysis data (N = 3,994,872) were obtained from CDC and NCHS' 2014 Natality public data file. The sample was split into independent training and validation cohorts for model generation and model assessment, respectively. Logistic regression and CART models were used to examine potential ePTB risk predictors and their interactions, including mothers' age, nativity, race, Hispanic origin, marital status, education, pre-pregnancy smoking status, pre-pregnancy BMI, pre-pregnancy diabetes status, pre-pregnancy hypertension status, previous preterm birth status, infertility treatment usage status, fertility enhancing drug usage status, and delivery payment source. Both logistic regression models with either 14 or 10 ePTB risk factors produced the same C-index (0.646) based on the training cohort. The C-index of the logistic regression model based on 10 predictors was 0.645 for the validation cohort. Both C-indexes indicated a good discrimination and acceptable model fit. The CART model identified preterm birth history and race as the most important risk factors, and revealed that the subgroup with a preterm birth history and a race designation as Black had the highest risk for ePTB. The c-index and misclassification rate were 0.579 and 0.034 for the training cohort, and 0.578 and 0.034 for the validation cohort, respectively. This study revealed 14 maternal characteristic variables that reliably identified risk for ePTB through either logistic regression model and/or a CART model. Moreover, both models efficiently identify risk subgroups for further enrichment clinical trial design.

Factors associated with negative T-SPOT.TB results among smear-negative tuberculosis patients in China.

PubMed

Kang, Wanli; Wu, Meiying; Yang, Kunyun; Ertai, A; Wu, Shucai; Geng, Shujun; Li, Zhihui; Li, Mingwu; Pang, Yu; Tang, Shenjie

2018-03-09

We compared the positive rates of T-SPOT.TB and bacterial culture in the smear-negative PTB, and analyzed the factors affecting the results of negative T-SPOT.TB and bacterial culture. Retrospective evaluation of data from smear-negative PTB patients who underwent T-SPOT.TB and bacterial culture were done. The agreement and concordance were analyzed between T-SPOT.TB and bacterial culture. Multivariable logistic regression analysis was used to explore the factors associated with positive results of T-SPOT.TB and bacterial culture in smear-negative PTB. 858 eligible smear-negative PTB patients were included in the study. The agreement rate was 25.6% (22.7~28.5%) between T-SPOT.TB and bacterial culture in smear- negative PTB patients. The positive rate of T-SPOT.TB was higher than that of bacterial culture in smear-negative PTB patients (p < 0.001). There were nearly no concordance between T-SPOT.TB and bacterial culture (p > 0.05). Using multivariable logistic regression analysis we found that older age ≥ 60 years (OR = 0.469, 95% CI: 0.287-0.768) and decreased albumin (OR = 0.614, 95% CI: 0.380-0.992) were associated with negative diagnostic results of T-SPOT.TB in smear-negative PTB patients. Female (OR = 0.654, 95% CI: 0.431-0.992) were associated with negative diagnostic results of bacteria culture in smear-negative PTB patients. Our results indicated that the older age and decreased albumin were independently associated with negative T-SPOT.TB responses.

Spatio-temporal analysis of preterm birth in Portugal and its relation with environmental variables

NASA Astrophysics Data System (ADS)

Oliveira, M.; Teodoro, Ana C.; Freitas, A.; Bernardes, J.; Gonçalves, H.

2016-10-01

Preterm birth (PTB), one of the major concerns in obstetrics, is conventionally defined as the delivery of a live infant before 37 completed weeks of gestation, and one of its causes may be environmental factors. Remote sensing is a valuable approach for monitoring environmental variables, including in health sciences. In this work, remote sensing data were used to explore the relation of the environment with PTB. Time-series with monthly rates of male/female ratio and PTB were obtained from Portugal in 2000-2014. The environmental variables included in this study were monthly mean temperatures (T), relative humidity (RH), NDVI, concentrations of NO2 and PM10 in 2003-2008. A temporal and spatial analysis of each health-related and environmental variable was performed, as well as their correlation. PTB has been increasing over time, from below 5% in 2000 to around 7% in 2014, with predominance of higher rates in districts with larger population. From 2003 to 2008, T and PM10 decreased significantly. A positive and significant correlation was found between male/female ratio and NO2 and RH, and to a lesser extent with PM10 and NDVI. PTB was also positively and significantly correlated with NO2 and T, and to a lesser extent with RH and PM10. These preliminary results suggest an association of PTB with most of the environmental variables studied, showing that more polluted and populated districts have higher rates of PTB. Further studies are warranted to explore interaction between the considered environmental factors and other variables related with risk for PTB.

Explaining Ethnic Disparities in Preterm Birth in Argentina and Ecuador

PubMed Central

Wehby, George L.; Pawluk, Mariela; Nyarko, Kwame A.; López-Camelo, Jorge S.

2017-01-01

Background Little is understood about racial/ethnic disparities in infant health in South America. We quantified the extent to which the disparity in preterm birth rate (PTB; < 37 gestational weeks) between infants of Native only ancestry and those of European only ancestry in Argentina and Ecuador are explained by household socioeconomic, demographic, healthcare use, and geographic location indicators. Methods The samples included 5199 infants born between 2000 and 2011 from Argentina and 1579 infants born between 2001 and 2011 from Ecuador. An Oaxaca-Blinder type decomposition model adapted to binary outcomes was estimated to explain the disparity in PTB risk across groups of variables and specific variables. Results Maternal use of prenatal care services significantly explained the PTB disparity, by nearly 57% and 30% in Argentina and Ecuador, respectively. Household socioeconomic status explained an additional 26% of the PTB disparity in Argentina. Conclusions Differences in maternal use of prenatal care may partly explain ethnic disparities in PTB in Argentina and Ecuador. Improving access to prenatal care may reduce ethnic disparities in PTB risk in these countries. PMID:27875924

Sociodemographic, Epidemiological, and Clinical Risk Factors for Childhood Pulmonary Tuberculosis in Severely Malnourished Children Presenting With Pneumonia

PubMed Central

Ahmed, Tahmeed; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Bardhan, Pradip Kumar; Faruque, Abu Syeed Golam; Das, Sumon Kumar; Salam, Mohammed Abdus

2015-01-01

We aimed to evaluate sociodemographic, epidemiological, and clinical risk factors for pulmonary tuberculosis (PTB) in children presenting with severe acute malnutrition (SAM) and pneumonia. Children aged 0 to 59 months with SAM and radiologic pneumonia from April 2011 to July 2012 were studied in Bangladesh. Children with confirmed PTB (by culture and/or X-pert MTB/RIF) (cases = 27) and without PTB (controls = 81; randomly selected from 378 children) were compared. The cases more often had the history of contact with active PTB patient (P < .01) and exposure to cigarette smoke (P = .04) compared with the controls. In logistic regression analysis, after adjusting for potential confounders, the cases were independently associated with working mother (P = .05) and positive tuberculin skin test (TST; P = .02). Thus, pneumonia in SAM children is a common presentation of PTB and further highlights the importance of the use of simple TST and/or history of contact with active TB patients in diagnosing PTB in such children, especially in resource-limited settings. PMID:27335971

An overview of racial disparities in preterm birth rates: caused by infection or inflammatory response?

PubMed Central

MENON, RAMKUMAR; DUNLOP, ANNE L.; KRAMER, MICHAEL R.; FORTUNATO, STEPHEN J.; HOGUE, CAROL J.

2017-01-01

Infection has been hypothesized to be one of the factors associated with spontaneous preterm birth (PTB) and with the racial disparity in rates of PTB between African American and Caucasian women. However, recent findings refute the generalizability of the role of infection and inflammation. African Americans have an increased incidence of PTB in the setting of intraamniotic infection, periodontal disease, and bacterial vaginosis compared to Caucasians. Herein we report variability in infection- and inflammation-related factors based on race/ethnicity. For African American women, an imbalance in the host proinflammatory response seems to contribute to infection-associated PTB, as evidenced by a greater presence of inflammatory mediators with limited or reduced presence of immune balancing factors. This may be attributed to differences in the genetic variants associated with PTB between African Americans and Caucasians. We argue that infection may not be a cause of racial disparity but in association with other risk factors such as stress, nutritional deficiency, and differences in genetic variations in PTB, pathways and their complex interactions may produce differential inflammatory responses that may contribute to racial disparity. PMID:21615712

The role of socioeconomic factors in Black-White disparities in preterm birth.

PubMed

Braveman, Paula A; Heck, Katherine; Egerter, Susan; Marchi, Kristen S; Dominguez, Tyan Parker; Cubbin, Catherine; Fingar, Kathryn; Pearson, Jay A; Curtis, Michael

2015-04-01

We investigated the role of socioeconomic factors in Black-White disparities in preterm birth (PTB). We used the population-based California Maternal and Infant Health Assessment survey and birth certificate data on 10 400 US-born Black and White California residents who gave birth during 2003 to 2010 to examine rates and relative likelihoods of PTB among Black versus White women, with adjustment for multiple socioeconomic factors and covariables. Greater socioeconomic advantage was generally associated with lower PTB rates among White but not Black women. There were no significant Black-White disparities within the most socioeconomically disadvantaged subgroups; Black-White disparities were seen only within more advantaged subgroups. Socioeconomic factors play an important but complex role in PTB disparities. The absence of Black-White disparities in PTB within certain socioeconomic subgroups, alongside substantial disparities within others, suggests that social factors moderate the disparity. Further research should explore social factors suggested by the literature-including life course socioeconomic experiences and racism-related stress, and the biological pathways through which they operate-as potential contributors to PTB among Black and White women with different levels of social advantage.

Residential segregation, political representation, and preterm birth among U.S.- and foreign-born Black women in the U.S. 2008-2010.

PubMed

Margerison-Zilko, Claire; Perez-Patron, Maria; Cubbin, Catherine

2017-07-01

Although racial residential segregation is associated with preterm birth (PTB) among non-Hispanic black (NHB) women in the U.S., prior work suggests that increased black political power arising from segregation may be protective for infant health. We examined associations between residential segregation, black political representation, and preterm birth (PTB) among U.S- and foreign-born NHB women in major U.S. cities using birth certificate data from 2008 to 2010 (n=861,450). Each 10-unit increase in segregation was associated with 3-6% increases in odds of PTB for both U.S.- and foreign-born NHB women. Black political representation was not associated with PTB and did not moderate the association between residential segregation and PTB. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pseudotachylitic breccia from the Dhala impact structure, north-central India: Texture, mineralogy and geochemical characterization

NASA Astrophysics Data System (ADS)

Pati, J. K.; Reimold, W. U.; Greshake, A.; Schmitt, R. T.; Koeberl, C.; Pati, P.; Prakash, K.

2015-05-01

Pseudotachylitic breccia (PTB) occurs in a drill core from the crater floor of the 11 km diameter, Proterozoic Dhala impact structure, India. PTBs were intersected in late Archean granitoids between 348.15 m and 502.55 m depth in the MCB-10 drill core from the center of the Dhala structure. The breccias comprise both cataclastic-matrix as well as melt breccias. The presence of microlites and vesicles in the groundmass and a widely observed flow fabric in the PTB support the presence of melt in the groundmass of some samples. Clasts in PTB are derived from the Archean granitoid basement. PTB matrix, the matrix of impact melt breccia also occurring between 256.50 m and 502.55 m depth, and the target granitoids vary in terms of silica, total alkali, magnesium and iron oxide contents. Chondrite-normalized REE patterns of PTB and target granitoids are similar, but the elemental abundances in the PTB are lower. The restricted size of PTB as veins and pods of up to 2.5 cm width, their occurrence at varied depths over a core length of 150 m, the clast population, and the chemical relationships between PTB and their host rocks all suggest the derivation of these breccias locally from the fractured basement granitoids involving in-situ melting. We favor that this took place due to rapid decompression during the collapse and modification stage of impact cratering, with, locally, additional energy input from frictional heating. Locally, amphibolite and dioritic mylonite occur in the host granitoids and their admixture could have contributed to the comparatively more mafic composition of PTB. Alteration of these crater floor rocks could have involved preferential reduction of silica and alkali element abundances, possibly due to impact-induced hydrothermal activity at crater floor level. This process, too, could have resulted in more mafic compositions.

Lower rates of preterm birth in women of Arab ancestry: an epidemiologic paradox--Michigan, 1993-2002.

PubMed

El Reda, Darline K; Grigorescu, Violanda; Posner, Samuel F; Davis-Harrier, Amanda

2007-11-01

Preterm birth (PTB), <37 weeks gestation, occurs in 12.1% of live births annually and is associated with significant morbidity and mortality in the United States. Racial/ethnic subgroups are disproportionately affected by PTB. Michigan is home to one of the largest Arab-American communities in the country; however, little is known about PTB in this population. This study examined the maternal demographic profile and risk factors of preterm birth (PTB) among foreign-born and US-born women of Arab ancestry relative to US-born Whites in Michigan. Using Michigan Vital Statistics data, we examined correlates of PTB for primiparous U.S.-born white (n = 205,749), U.S.-born Arab (n=1,697), and foreign-born Arab (n=5,997) women who had had a live-born singleton infant during 1993-2002. We examined variables commonly reported to be associated with PTB, including mother's age and education; insurance type; marital status of parents; receipt of prenatal care; mother's chronic hypertension, diabetes, and tobacco use; and infant sex. Foreign-born Arabs are less educated and more likely to be on Medicaid, and they receive less prenatal care than US-born Whites. Prevalence of PTB was 8.5, 8.0, and 7.5% for US-born Whites, US-born Arabs, and foreign-born Arabs, respectively. Pregnancy-related hypertension was the only predictor of PTB that these three groups had in common: Adjusted Odds Ratio (AOR)=2.1 (95% Confidence Interval (CI)=1.99, 2.21), AOR=2.6 (95% CI=1.24, 5.51), and AOR=2.6 (95% CI=1.55, 4.31) for US-born whites, US-born Arabs, and foreign-born Arabs, respectively. Foreign-born Arab women in Michigan have a higher-risk maternal demographic profile than that of their US-born white counterparts; however, their prevalence of PTB is lower, which is consistent with the epidemiologic paradox reported among foreign-born Hispanic women.

Fetal DNA methylation of autism spectrum disorders candidate genes: association with spontaneous preterm birth.

PubMed

Behnia, Fara; Parets, Sasha E; Kechichian, Talar; Yin, Huaizhi; Dutta, Eryn H; Saade, George R; Smith, Alicia K; Menon, Ramkumar

2015-04-01

Autism spectrum disorder (ASD) is associated with preterm birth (PTB), although the reason underlying this relationship is still unclear. Our objective was to examine DNA methylation patterns of 4 ASD candidate genes in human fetal membranes from spontaneous PTB and uncomplicated term birth. A literature search for genes that have been implicated in ASD yielded 14 candidate genes (OXTR, SHANK3, BCL2, RORA, EN2, RELN, MECP2, AUTS2, NLGN3, NRXN1, SLC6A4, UBE3A, GABA, AFF2) that were epigenetically modified in relation to ASD. DNA methylation in fetal leukocyte DNA in 4 of these genes (OXTR, SHANK3, BCL2, and RORA) was associated with PTB in a previous study. This study evaluated DNA methylation, transcription (reverse transcription polymerase chain reaction), and translation patterns (immunostaining and Western blot) in fetal membrane from term labor (n = 14), term not in labor (TNIL; n = 29), and spontaneous preterm birth (PTB; n = 27). Statistical analysis was performed with analysis of variance; a probability value of < .05 was significant. Higher methylation of the OXTR promoter was seen in fetal membranes from PTB, compared with term labor or TNIL. No other gene showed any methylation differences among groups. Expression of OXTR was not different among groups, but the 70 kDa OXTR protein was seen only in PTB, and immunostaining was more intense in PTB amniocytes than term labor or TNIL. Among the 4 genes that were studied, fetal membranes from PTB demonstrate differences in OXTR methylation and regulation and expression, which suggest that epigenetic alteration of this gene in fetal membrane may likely be indicating an in utero programing of this gene and serve as a surrogate in a subset of PTB. The usefulness of OXTR hypermethylation as a surrogate for a link to ASD should be further evaluated in longitudinal and in vitro studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Urinary Bisphenol A Levels during Pregnancy and Risk of Preterm Birth

PubMed Central

Ferguson, Kelly K.; Mukherjee, Bhramar; McElrath, Thomas F.; Meeker, John D.

2015-01-01

Background Preterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regard to PTB. Objectives In the present study we examined the relationship between longitudinally measured BPA exposure during gestation and PTB. Methods A nested case–control study was performed from women enrolled in a prospective birth cohort study at Brigham and Women’s Hospital in Boston, Massachusetts, during 2006–2008. Urine samples were analyzed for BPA concentrations at a minimum of three time points during pregnancy on 130 cases of PTB and 352 randomly assigned controls. Clinical classifications of PTB were defined as “spontaneous,” which was preceded by spontaneous preterm labor or preterm premature rupture of membranes, or “placental,” which was preceded by preeclampsia or intrauterine growth restriction. Results Geometric mean concentrations of BPA did not differ significantly between cases and controls. In adjusted models, urinary BPA averaged across pregnancy was not significantly associated with PTB. When examining clinical classifications of PTB, urinary BPA late in pregnancy was significantly associated with increased odds of delivering a spontaneous PTB. After stratification on infant’s sex, averaged BPA exposure during pregnancy was associated with significantly increased odds of being delivered preterm among females, but not males. Conclusions These results provide little evidence of a relationship between BPA and prematurity, though further research may be warranted given the generalizability of participant recruitment from a tertiary teaching hospital, limited sample size, and significant associations among females and within the clinical subcategories of PTB. Citation Cantonwine DE, Ferguson KK, Mukherjee B, McElrath TF, Meeker JD. 2015. Urinary bisphenol A levels during pregnancy and risk of preterm birth. Environ Health Perspect 123:895–901; http://dx.doi.org/10.1289/ehp.1408126 PMID:25815860

Seasonal variations in tuberculosis diagnosis among HIV-positive individuals in Southern Africa: analysis of cohort studies at antiretroviral treatment programmes

PubMed Central

Ballif, Marie; Zürcher, Kathrin; Reid, Stewart E; Boulle, Andrew; Fox, Matthew P; Prozesky, Hans W; Chimbetete, Cleophas; Egger, Matthias; Fenner, Lukas

2018-01-01

Objectives Seasonal variations in tuberculosis diagnoses have been attributed to seasonal climatic changes and indoor crowding during colder winter months. We investigated trends in pulmonary tuberculosis (PTB) diagnosis at antiretroviral therapy (ART) programmes in Southern Africa. Setting Five ART programmes participating in the International Epidemiology Database to Evaluate AIDS in South Africa, Zambia and Zimbabwe. Participants We analysed data of 331 634 HIV-positive adults (>15 years), who initiated ART between January 2004 and December 2014. Primary outcome measure We calculated aggregated averages in monthly counts of PTB diagnoses and ART initiations. To account for time trends, we compared deviations of monthly event counts to yearly averages, and calculated correlation coefficients. We used multivariable regressions to assess associations between deviations of monthly ART initiation and PTB diagnosis counts from yearly averages, adjusted for monthly air temperatures and geographical latitude. As controls, we used Kaposi sarcoma and extrapulmonary tuberculosis (EPTB) diagnoses. Results All programmes showed monthly variations in PTB diagnoses that paralleled fluctuations in ART initiations, with recurrent patterns across 2004–2014. The strongest drops in PTB diagnoses occurred in December, followed by April–May in Zimbabwe and South Africa. This corresponded to holiday seasons, when clinical activities are reduced. We observed little monthly variation in ART initiations and PTB diagnoses in Zambia. Correlation coefficients supported parallel trends in ART initiations and PTB diagnoses (correlation coefficient: 0.28, 95% CI 0.21 to 0.35, P<0.001). Monthly temperatures and latitude did not substantially change regression coefficients between ART initiations and PTB diagnoses. Trends in Kaposi sarcoma and EPTB diagnoses similarly followed changes in ART initiations throughout the year. Conclusions Monthly variations in PTB diagnosis at ART programmes in Southern Africa likely occurred regardless of seasonal variations in temperatures or latitude and reflected fluctuations in clinical activities and changes in health-seeking behaviour throughout the year, rather than climatic factors. PMID:29330173

Photophysical and morphological implications of single-strand conjugated polymer folding in solution

DOE PAGES

Fauvell, Thomas J.; Zheng, Tianyue; Jackson, Nicholas E.; ...

2016-04-08

Organic semiconductors have garnered substantial interest in optoelectronics, but their device performances exhibit strong dependencies on material crystallinity and packing. In an effort to understand the interactions dictating the morphological and photophysical properties of a high-performing photovoltaic polymer, PTB7, a series of short oligomers and low molecular weight polymers of PTB7 were synthesized. Chain-length dependent optical studies of these oligomers demonstrate that PTB7’s low-energy visible absorption is largely due to self-aggregation-induced ordering, rather than in-chain charge transfer, as previously thought. By examining molecular weight and concentration dependent optical properties, supplemented by molecular dynamics simulations, we attribute polymeric PTB7’s unique midgapmore » fluorescence and concentration independent absorption spectrum to an interplay between low molecular weight unaggregated strands and high-molecular weight self-aggregated (folded) strands. Specifically, we propose that the onset of PTB7 self-folding occurs between 7 and 13 repeat units, but the aggregates characteristic of polymeric PTB7 only develop at lengths of ~30 repeat units. Atomistic molecular dynamics simulations of PTB7 corroborate these conclusions, and a simple relation is proposed which quantifies the free-energy of conjugated polymer folding. Lastly, this study provides detailed guidance in the design of intra- and interchain contributions to the photophysical and morphological properties of polymeric semiconductors.« less

Extreme maternal education and preterm birth: time-to-event analysis of age and nativity-dependent risks.

PubMed

Auger, Nathalie; Abrahamowicz, Michal; Park, Alison L; Wynant, Willy

2013-01-01

Increasing numbers of women achieve extremely high education, but the association with preterm birth (PTB) is poorly understood, especially over the life course. We sought to determine how very high educational attainment is associated with PTB, and to assess differences by maternal age and nativity. Data included singleton live births to mothers aged ≥ 20 years in metropolitan areas of Québec, Canada, from 1995 to 2005 (n = 537,525). Hazard ratios of PTB (<37 gestational weeks) were estimated over the continuous range of education (0-30 years) according to maternal age (20-24, 25-29, 30-34, ≥ 35 years) and nativity in a flexible survival model. The relationship between education and PTB was not linear, but suggested that extremely high education was not as protective against PTB as slightly lower education. Education thresholds that offered maximum protection increased with maternal age, and were lower for Canadian-born (17-21 years of education) than foreign-born (22-25 years of education) mothers. Extremely high education did not confer more protection against PTB than slightly lower education, and associations varied over the life course. The threshold number of years of education most protective against PTB: (1) increased with maternal age, especially for Canadian-born mothers, and (2) was higher for foreign-born mothers. Copyright © 2013 Elsevier Inc. All rights reserved.

Oriented thin films of mixture of a low-bandgap polymer and a fullerene derivative prepared by friction-transfer method

NASA Astrophysics Data System (ADS)

Tanigaki, Nobutaka; Mizokuro, Toshiko; Miyadera, Tetsuhiko; Shibata, Yousei; Koganezawa, Tomoyuki

2018-02-01

We have been studying oriented thin films of polymers fabricated by the friction-transfer method, which allows the alignment of a variety of conjugated polymers into highly oriented films. In this study, we prepared oriented blend films of a mixture of a low-bandgap polymer, poly{4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b‧]dithiophene-2,6-diyl-alt-3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophene-4,6-diyl} (PTB7), and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM), which is a promising combination for application in organic solar cells. We obtained oriented blend films of PTB7 and PC71BM by the friction-transfer method from a solid block. Polarized UV-visible spectra show that the PTB7 chains were aligned parallel to the friction direction in the blend films. Grazing-incidence X-ray diffraction (GIXD) studies with synchrotron radiation suggested that the preferred orientation of PTB7 crystallites was face-on in the blend films. The GIXD results also showed the high uniaxial orientation of PTB7 chains in blend films. Photovoltaic devices were fabricated using the friction-transferred blend films of the PTB7 and PC71BM. These bulk heterojunction devices showed better performance than planar heterojunction devices fabricated using pure friction-transferred PTB7 films.

p53 coordinates decidual sestrin 2/AMPK/mTORC1 signaling to govern parturition timing.

PubMed

Deng, Wenbo; Cha, Jeeyeon; Yuan, Jia; Haraguchi, Hirofumi; Bartos, Amanda; Leishman, Emma; Viollet, Benoit; Bradshaw, Heather B; Hirota, Yasushi; Dey, Sudhansu K

2016-08-01

Inflammation and oxidative stress are known risk factors for preterm birth (PTB); however, the mechanisms and pathways that influence this condition are not fully described. Previously, we showed that mTORC1 signaling is increased in mice harboring a uterine-specific deletion of transformation-related protein 53 (p53d/d mice), which exhibit premature decidual senescence that triggers spontaneous and inflammation-induced PTB. Treatment with the mTORC1 inhibitor rapamycin reduced the incidence of PTB in the p53d/d mice. Decidual senescence with heightened mTORC1 signaling is also a signature of human PTB. Here, we have identified an underlying mechanism for PTB and a potential therapeutic strategy for treating the condition. Treatment of pregnant p53d/d mice with either the antidiabetic drug metformin or the antioxidant resveratrol activated AMPK signaling and inhibited mTORC1 signaling in decidual cells. Both metformin and resveratrol protected against spontaneous and inflammation-induced PTB in p53d/d females. Using multiple approaches, we determined that p53 interacts with sestrins to coordinate an inverse relationship between AMPK and mTORC1 signaling that determines parturition timing. This signature was also observed in human decidual cells. Together, these results reveal that p53-dependent coordination of AMPK and mTORC1 signaling controls parturition timing and suggest that metformin and resveratrol have therapeutic potential to prevent PTB.

Short and inflamed cervix predicts spontaneous preterm birth (COLIBRI study).

PubMed

Raiche, Evelyne; Ouellet, Annie; Berthiaume, Maryse; Rousseau, Éric; Pasquier, Jean-Charles

2014-07-01

To develop a new strategy of predicting spontaneous preterm birth (sPTB) by combination of transvaginal ultrasound (TVUS) assessment and inflammatory proteins detection in vaginal secretions. Prospective study of 87 women referred for cervical length assessment with a standardized TVUS combined to vaginal secretions sampling. Samples were analyzed for presence of 10 cytokines. Main outcome was sPTB (<37 weeks of gestation). Associations were assessed with the chi-square, Fisher's exact test (p < 0.05) and Wald's logistic regression. sPTB occurred in 25.3% of women at a median gestational age of 35.6 weeks of gestation. Short cervix (<25 mm) (n = 24) was associated with sPTB (p < 0.01) as interleukine (IL)-1β, IL-8 and IL-10 in vaginal secretions (p < 0.05). In multivariate analysis, short cervix and IL-8 in vaginal secretions were independently associated with sPTB (OR 3.58 (95%CI 1.02; 12.61) and 14.55 (95%CI 1.64; 128.83), respectively) as their combination (OR 4.33 (95%CI 1.25; 14.95)). By categorizing cervical length by presence of IL-8, sPTB occurred in 55.6% of women with a short inflamed cervix. COLIBRI study used a novel, single-step method of vaginal secretions sampling during TVUS and demonstrated that combination of short cervix and IL-8 in vaginal secretions is a promising sPTB predictive test.

The Haemophilus influenzae Hap Autotransporter Binds to Fibronectin, Laminin, and Collagen IV

PubMed Central

Fink, Doran L.; Green, Bruce A.; St. Geme III, Joseph W.

2002-01-01

Nontypeable Haemophilus influenzae (NTHI) initiates infection by colonizing the upper respiratory tract mucosa. NTHI disease frequently occurs in the context of respiratory tract inflammation, where organisms encounter damaged epithelium and exposed basement membrane. In this study, we examined interactions between the H. influenzae Hap adhesin and selected extracellular matrix proteins. Hap is an autotransporter protein that undergoes autoproteolytic cleavage, with release of the adhesive passenger domain, Haps, from the bacterial cell surface. We found that Hap promotes bacterial adherence to purified fibronectin, laminin, and collagen IV and that Hap-mediated adherence is enhanced by inhibition of autoproteolysis. Adherence is inhibited by pretreatment of bacteria with a polyclonal antiserum recognizing Haps. Purified Haps binds with high affinity to fibronectin, laminin, and collagen IV but not to collagen II. Binding of Haps to fibronectin involves interaction with the 45-kDa gelatin-binding domain but not the 30-kDa heparin-binding domain of fibronectin. Taken together, these observations suggest that interactions between Hap and extracellular matrix proteins may play an important role in NTHI colonization of the respiratory tract. PMID:12183535

Preterm birth in the Inuit and First Nations populations of Québec, Canada, 1981-2008.

PubMed

Auger, Nathalie; Fon Sing, Mélanie; Park, Alison L; Lo, Ernest; Trempe, Normand; Luo, Zhong-Cheng

2012-03-24

To evaluate preterm birth (PTB) for Inuit and First Nations vs. non-Indigenous populations in the province of Québec, Canada. Retrospective cohort study. We evaluated singleton live births for Québec residents, 1981-2008 (n = 2,310,466). Municipality of residence (Inuit-inhabited, First Nations-inhabited, rest of Québec) and language (Inuit, First Nations, French/English) were used to identify Inuit and First Nations births. The outcome was PTB (<37 completed weeks). Cox proportional hazards regression was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) of PTB, adjusting for maternal age, education, marital status, parity and birth year. PTB rates were higher for Inuit language speakers in Inuit-inhabited areas and the rest of Québec compared with French/English speakers in the rest of Québec, and disparities persisted over time. Relative to French/English speakers in the rest of Québec, Inuit language speakers in the rest of Québec had the highest risk of PTB (HR 1.98, 95% CI: 1.62-2.41). The risk was also elevated for Inuit language speakers in Inuit-inhabited areas, though to a lesser extent (HR 1.29, 95% CI: 1.18-1.41). In contrast, First Nations language speakers in First Nations-inhabited areas and the rest of Québec had similar or lower risks of PTB relative to French/English speakers in the rest of Québec. Inuit populations, especially those outside Inuit-inhabited areas, have persistently elevated risks of PTB, indicating a need for strategies to prevent PTB in this population.

Preterm birth in the Inuit and First Nations populations of Québec, Canada, 1981–2008

PubMed Central

Auger, Nathalie; Sing, Mélanie Fon; Park, Alison L.; Lo, Ernest; Trempe, Normand; Luo, Zhong-Cheng

2012-01-01

Objectives To evaluate preterm birth (PTB) for Inuit and First Nations vs. non-Indigenous populations in the province of Québec, Canada. Study design Retrospective cohort study. Methods We evaluated singleton live births for Québec residents, 1981–2008 (n =2,310,466). Municipality of residence (Inuit-inhabited, First Nations-inhabited, rest of Québec) and language (Inuit, First Nations, French/English) were used to identify Inuit and First Nations births. The outcome was PTB (<37 completed weeks). Cox proportional hazards regression was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) of PTB, adjusting for maternal age, education, marital status, parity and birth year. Results PTB rates were higher for Inuit language speakers in Inuit-inhabited areas and the rest of Québec compared with French/English speakers in the rest of Québec, and disparities persisted over time. Relative to French/English speakers in the rest of Québec, Inuit language speakers in the rest of Québec had the highest risk of PTB (HR 1.98, 95% CI: 1.62–2.41). The risk was also elevated for Inuit language speakers in Inuit-inhabited areas, though to a lesser extent (HR 1.29, 95% CI: 1.18–1.41). In contrast, First Nations language speakers in First Nations-inhabited areas and the rest of Québec had similar or lower risks of PTB relative to French/English speakers in the rest of Québec. Conclusions Inuit populations, especially those outside Inuit-inhabited areas, have persistently elevated risks of PTB, indicating a need for strategies to prevent PTB in this population. PMID:22456035

Identification of a Key Gene Involved in Branched-Chain Short Fatty Acids Formation in Natto by Transcriptional Analysis and Enzymatic Characterization in Bacillus subtilis.

PubMed

Hong, Chenlu; Chen, Yangyang; Li, Lu; Chen, Shouwen; Wei, Xuetuan

2017-03-01

Natto as a fermented soybean product has many health benefits for human due to its rich nutritional and functional components. However, the unpleasant odor of natto, caused by the formation of branched-chain short fatty acids (BCFAs), prohibits the wide acceptance of natto products. This work is to identify the key gene of BCFAs formation and develop the guidance to reduce natto odor. Transcriptional analysis of BCFAs synthesis pathway genes was conducted in two Bacillus subtilis strains with obvious different BCFAs synthesis abilities. The transcriptional levels of bcd, bkdAA, and ptb in B. subtilis H-9 were 2.7-fold, 0.7-fold, and 8.9-fold higher than that of B. subtilis H-4, respectively. Therefore, the ptb gene with the highest transcriptional change was considered as the key gene in BCFAs synthesis. The ptb encoded enzyme Ptb was further characterized by inducible expression in Escherichia coli. The recombinant Ptb protein (about 32 kDa) was verified by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis analysis. The catalysis functions of Ptb were confirmed on substrates of isovaleryl-CoA and isobutyryl-CoA, and the higher catalysis efficiency of Ptb on isovaleryl-CoA explained the higher level of isovaleric acid in natto. The optimal activities of Ptb were observed at 50 °C and pH 8.0, and the enzymatic activity was inhibited by Ca 2+ , Zn 2+ , Ba 2+ , Mn 2+ , Cu 2+ , SDS, and EDTA. Collectively, this study reports a key gene responsible for BCFAs formation in natto fermentation and provides potential strategies to solve the odor problem.

Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta-analysis.

PubMed

Jarde, A; Lutsiv, O; Park, C K; Beyene, J; Dodd, J M; Barrett, J; Shah, P S; Cook, J L; Saito, S; Biringer, A B; Sabatino, L; Giglia, L; Han, Z; Staub, K; Mundle, W; Chamberlain, J; McDonald, S D

2017-07-01

Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it. To compare progesterone, cerclage and pessary, determine their relative effects and rank them. We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews. We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study. We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT). We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks. Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae. Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis. © 2017 Royal College of Obstetricians and Gynaecologists.

Comparison of absorbed-dose-to-water units for Co-60 and high-energy x-rays between PTB and LNE-LNHB

NASA Astrophysics Data System (ADS)

Delaunay, F.; Kapsch, R.-P.; Gouriou, J.; Illemann, J.; Krauss, A.; Le Roy, M.; Ostrowsky, A.; Sommier, L.; Vermesse, D.

2012-10-01

During the Euramet project JRP7 ‘External Beam Cancer Therapy’, PTB and LNE-LNHB used primary standards to determine the absorbed dose to water under IMRT conditions (in small fields). PTB used a water calorimeter to determine the absorbed-dose-to-water references in 6 MV and 10 MV beams for field sizes of 10 cm × 10 cm and 3 cm × 3 cm while LNE-LNHB used graphite calorimeters in 6 MV and 12 MV beams for field sizes of 10 cm × 10 cm, 4 cm × 4 cm and 2 cm × 2 cm. The purpose of this study is to compare PTB and LNE-LNHB new absorbed-dose-to-water references. LNE-LNHB sent an Exradin A1SL ionization chamber traceable to its primary standard to the PTB for calibration in 60Co and in linac beams and PTB sent a PTW 31010 ionization chamber traceable to its primary standard to LNE-LNHB for calibration in 60Co and in linac beams. Calculated Sw,air will be used as beam quality specifier for the ionization chamber comparison at different field sizes. The standard uncertainties (k = 1) of PTB and LNE-LNHB calibration coefficients lie respectively between 0.25% (60Co) and 0.40% (linac) and between 0.29% and 0.46%. PTB and LNE-LNHB absorbed-dose-to-water references developed for this project, based respectively on water calorimetry and on graphite calorimetry, agree within 1.5 standard deviations for field size of 10 cm × 10 cm down to 2 cm × 2 cm and for beams of 6 MV to 10 MV.

Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum

PubMed Central

Park, Soochul

2016-01-01

EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is the Anks1a PTB adaptor. However, the precise role of Anks1a in EphA2-mediated tumorigenesis is unclear. We demonstrated that Anks1a localizes to the ER upon phosphorylation and that the Ankyrin repeats and PTB of Anks1a bind to EphA2 and Sec23, respectively. Thus, Anks1a facilitates the selective packaging of EphA2 into COPII vesicles. Additionally, Anks1a knockout mice, a phenocopy of EphA2 knockout mice, exhibited markedly reduced ErbB2-induced breast tumorigenesis. Strikingly, ErbB2 did not localize to the cell surface following Anks1a knockdown in primary mammary tumor cells over-expressing ErbB2. Importantly, EphA2 was critical for stabilizing ErbB2 through complex formation, but its interaction with Anks1a also facilitated ErbB2 loading into COPII carriers. These findings suggest a novel role for Anks1a in the molecular pathogenesis of breast tumors and possibly other human diseases. PMID:27802842

Preterm Birth and Prenatal Maternal Occupation: The Role of Hispanic Ethnicity and Nativity in a Population-Based Sample in Los Angeles, California

PubMed Central

Wilhelm, Michelle; Wang, Anthony; Ritz, Beate

2014-01-01

Objectives. We investigated preterm birth (PTB) in relation to maternal occupational exposure and whether effect measures were modified by Hispanic ethnicity and nativity in a population-based sample with high proportion of Hispanics. Methods. We used a case-control study (n = 2543) nested within a cohort of 58 316 births in Los Angeles County, California, in 2003. We categorized prenatal occupations using the US Census Occupation Codes and Classification System and developed a job exposure matrix. Odds ratios for PTB were estimated using logistic regression. Results. Odds ratios for PTB were increased for all women in health care practitioner and technical occupations, but the 95% confidence intervals included the null value; effects were more pronounced among Hispanics. We estimated elevated odds ratios for foreign-born Hispanic women in building and grounds cleaning and maintenance occupations. Shift work and physically demanding work affected births among US-born but not foreign-born Hispanics. Conclusions. Hispanic women are at particular risk for PTB related to adverse prenatal occupational exposure. Nativity may moderate these effects on PTB. Maternal occupational exposures likely contribute to ethnic disparities in PTB. PMID:24354840

The Role of Socioeconomic Factors in Black–White Disparities in Preterm Birth

PubMed Central

Heck, Katherine; Egerter, Susan; Marchi, Kristen S.; Dominguez, Tyan Parker; Cubbin, Catherine; Fingar, Kathryn; Pearson, Jay A.; Curtis, Michael

2015-01-01

Objectives. We investigated the role of socioeconomic factors in Black–White disparities in preterm birth (PTB). Methods. We used the population-based California Maternal and Infant Health Assessment survey and birth certificate data on 10 400 US-born Black and White California residents who gave birth during 2003 to 2010 to examine rates and relative likelihoods of PTB among Black versus White women, with adjustment for multiple socioeconomic factors and covariables. Results. Greater socioeconomic advantage was generally associated with lower PTB rates among White but not Black women. There were no significant Black–White disparities within the most socioeconomically disadvantaged subgroups; Black–White disparities were seen only within more advantaged subgroups. Conclusions. Socioeconomic factors play an important but complex role in PTB disparities. The absence of Black–White disparities in PTB within certain socioeconomic subgroups, alongside substantial disparities within others, suggests that social factors moderate the disparity. Further research should explore social factors suggested by the literature—including life course socioeconomic experiences and racism-related stress, and the biological pathways through which they operate—as potential contributors to PTB among Black and White women with different levels of social advantage. PMID:25211759

Risk factors for pre-term birth in a Canadian cohort of HIV-positive women: role of ritonavir boosting?

PubMed Central

Kakkar, Fatima; Boucoiran, Isabelle; Lamarre, Valerie; Ducruet, Thierry; Amre, Devendra; Soudeyns, Hugo; Lapointe, Normand; Boucher, Marc

2015-01-01

Background The risk of pre-term birth (PTB) associated with the use of protease inhibitors (PIs) during pregnancy remains a subject of debate. Recent data suggest that ritonavir boosting of PIs may play a specific role in the initiation of PTB, through an effect on the maternal–fetal adrenal axis. The primary objective of this study is to compare the risk of PTB among women treated with boosted PI versus non-boosted PIs during pregnancy. Methods Between 1988 and 2011, 705 HIV-positive women were enrolled into the Centre Maternel et Infantile sur le SIDA mother–infant cohort at Centre Hospitalier Universitaire Sainte-Justine in Montreal, Canada. Inclusion criteria for the study were: 1) attendance at a minimum of two antenatal obstetric visits and 2) singleton live birth, at 24 weeks gestational or older. The association between PTB (defined as delivery at <37 weeks gestational age), antiretroviral drug exposure and maternal risk factors was assessed retrospectively using logistic regression. Results A total of 525 mother–infant pairs were included in the analysis. Among them, PI-based combination anti-retroviral therapy was used in 37.4%, boosted PI based in 24.4%, non-nucleoside reverse transcriptase inhibitor (NNRTI) or nucleoside reverse transcriptase inhibitor based in 28.1%, and no treatment was given in 10.0% of cases. Overall, 13.5% of women experienced PTB. Among women treated with antiretroviral therapy, the risk of PTB was significantly higher among women who received boosted versus non-boosted PI (OR 2.01, 95% CI 1.02–3.97). This remained significant after adjusting for maternal age, delivery CD4 count, hepatitis C co-infection, history of previous PTB, and parity (aOR 2.17, 95% CI 1.05–4.51). There was no increased risk of PTB with the use of unboosted PIs as compared to NNRTI- or NRTI-based regimens. Conclusion While previous studies on the association between PTB and PI use have generally considered all PIs the same, our results would indicate a possible role of ritonavir boosting as a risk factor for PTB. Further work is needed to understand the pathophysiologic mechanisms involved, and to identify the safest ARV regimens to be used in pregnancy. PMID:26051165

Demographic, health services and socio-economic factors associated with pulmonary tuberculosis mortality in Los Altos Region of Chiapas, Mexico.

PubMed

Nájera-Ortiz, J C; Sánchez-Pérez, H J; Ochoa-Díaz, H; Arana-Cedeño, M; Lezama, Ma Salazar; Mateo, M Martín

2008-08-01

Chiapas is one of the Mexican states having the highest rates of Pulmonary Tuberculosis (PTB), due to the numerous factors impeding its management and control (poverty, poor housing and nutrition, shortage of health resources, among others). To analyse the PTB mortality of a cohort of patients in Los Altos Region of Chiapas, who had been diagnosed with PTB from January 1, 1998 to December 31, 2002; and, to identify demographic, socioeconomic and health services utilization factors, associated with death from PTB. Analysis of a cohort of patients aged over 14 years diagnosed with PTB in the above mentioned period (n = 431) in Los Altos region of Chiapas. The records of the Tuberculosis Programme were reviewed, and patients were located through a search attempting to locate them in their homes. Those found alive were interviewed and asked to provide sputum samples. In the case of deceased patients, a verbal autopsy was obtained from a member of their family. The records of the PTB Programme in the area were incomplete and erroneous in many cases. The results of the home follow-up visits were: 208 (48%) patients located alive, five of whom were still PTB positive (three with multi-drug resistance); 145 (34%) could not be located and 78 (18%) had already died. Apparently, in at least 40 cases, the deaths were associated with PTB. Of these forty, 33 (83%) died without having received any medical care. The factors associated with dying from PTB were: 45 and over years of age (OR = 1.3; 95% CI = 0.98-1.3), 0-3 schooling years (OR = 3.3; 95% CI = 1.1-9.6), engaged in agriculture (OR = 2.2; 95% CI = 1.1-4.4), not living in main villages of their municipality (OR = 1.2; 95% CI = 1.0-1.3), living in a rural community (OR = 2.7; 95% CI = 1.1-6.8), not having been treated in DOTS (OR = 1.2; 95% CI = 1.0-1.3) and having defaulted from treatment (OR = 11.5; 95% CI = 5.3-24.8). The high rate of mortality due to PTB observed constitutes a serious public health problem deserving attention. There is an urgent need to evaluate and restructure the Tuberculosis Programme in the studied area.

Interactions between environmental factors and maternal-fetal genetic variations: strategies to elucidate risks of preterm birth.

PubMed

Pereyra, Silvana; Bertoni, Bernardo; Sapiro, Rossana

2016-07-01

Preterm birth (PTB) is a complex disease in which medical, social, cultural, and hereditary factors contribute to the pathogenesis of this adverse event. Interactions between genes and environmental factors may complicate our understanding of the relative influence of both effects on PTB. To overcome this, we combined data obtained from a cohort of newborns and their mothers with multiplex analysis of inflammatory-related genes and several environmental risk factors of PTB to describe the environmental-genetic influence on PTB. The study aimed to investigate the association between maternal and fetal genetic variations in genes related to the inflammation pathway with PTB and to assess the interaction between environmental factors with these variations. We conducted a case-control study at the Pereira Rossell Hospital Center, Montevideo, Uruguay. The study included 143 mother-offspring dyads who delivered at preterm (gestational age<37 weeks) and 108 mother-offspring dyads who delivered at term. We used real-time PCR followed by a high-resolution melting analysis to simultaneously identify gene variations involved in inflammatory pathways in the context of environmental variables. The genes analyzed were: Toll-like receptor 4 (TLR4), Interleukin 6 (IL6), Interleukin 1 beta (IL1B) and Interleukin 12 receptor beta (IL12RB). We detected a significant interaction between IL1B rs16944 polymorphism in maternal samples and IL6 rs1800795 polymorphism in newborns, emphasizing the role of the interaction of maternal and fetal genomes in PTB. In addition, smoke exposure and premature rupture of membranes (PROM) were significantly different between the premature group and controls. IL1B and IL6 polymorphisms in mothers were significantly associated with PTB when controlling for smoke exposure. TLR4 polymorphism and PROM were significantly associated with PTB when controlling for PROM, but only in the case of severe PTB. Interactions between maternal and fetal genomes may influence the timing of birth. By incorporating environmental data, we revealed genetic associations with PTB, a finding not found when we analyzed genetic data alone. Our results stress the importance of studying the effect of genotype interactions between mothers and children in the context of environmental factors because they substantially contribute to phenotype variability. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Exposure to Elemental Carbon, Organic Carbon, Nitrate, and Sulfate Fractions of Fine Particulate Matter and Risk of Preterm Birth in New Jersey, Ohio, and Pennsylvania (2000–2005)

PubMed Central

Daniels, Julie L.; Messer, Lynne C.; Poole, Charles; Lobdell, Danelle T.

2015-01-01

Background Particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) has been consistently associated with preterm birth (PTB) to varying degrees, but roles of PM2.5 species have been less studied. Objective We estimated risk differences (RD) of PTB (reported per 106 pregnancies) associated with change in ambient concentrations of elemental carbon (EC), organic carbon (OC), nitrates (NO3), and sulfates (SO4). Methods From live birth certificates from three states, we constructed a cohort of singleton pregnancies at or beyond 20 weeks of gestation from 2000 through 2005 (n = 1,771,225; 8% PTB). We estimated mean species exposures for each week of gestation from monitor-corrected Community Multi-Scale Air Quality modeling data. RDs and 95% confidence intervals (CIs) for four PTB categories were estimated for each exposure using linear regression, adjusted for maternal race/ethnicity, marital status, education, age, smoking, maximum temperature, ozone, and season of conception. We also adjusted for other species in multi-species models. Results RDs varied by exposure window and outcome period. EC was positively associated with PTB after 27 and before 35 weeks of gestation. For example, for a 0.25-μg/m3 increase in EC exposure during gestational week 9, RD = 96 (95% CI: –20, 213) and RD = 145 (95% CI: –50, 341) for PTB during weeks 28–31 and 32–34, respectively. Associations with OCs were null or negative. RDs for NO3 were elevated with exposure in early weeks of gestation, and null in later weeks. RDs for SO4 exposure were positively associated with PTB, though magnitude varied across gestational weeks. We observed effect measure modification for associations between EC and PTB by race/ethnicity and smoking status. Conclusion EC and SO4 may contribute to associations between PM2.5 and PTB. Associations varied according to the timing of exposure and the timing of PTB. Citation Rappazzo KM, Daniels JL, Messer LC, Poole C, Lobdell DT. 2015. Exposure to elemental carbon, organic carbon, nitrate, and sulfate fractions of fine particulate matter and risk of preterm birth in New Jersey, Ohio, and Pennsylvania (2000–2005). Environ Health Perspect 123:1059–1065; http://dx.doi.org/10.1289/ehp.1408953 PMID:25910280

Directly observed treatment short course (DOTS) appears to have reduced the self-care role of the-pulmonary tuberculosis patient: evidence from a correlational study between personal health beliefs (PHB) and self-care practices (SCP).

PubMed

Gundani, Hv; Watyoka, H; Nyathi, C; Charumbira, A P

2010-01-01

To examine the relationship between personal health beliefs and self-care practices among 69 PTB patients aged 25 to 65 years at a tuberculosis clinic in Zimbabwe, in order to determine the role patients can play in self-care. Analysis of collected demographic data, personal health beliefs (PH B) and self-care practices (SCP) of PTB patients. Gwanda Provincial Hospital (GPH) Tuberculosis Clinic. PTB patients in the (GPH) register who were taking treatment. Key components of the study included administration of an interview schedule to 69 PTB patients on treatment, and the analysis and comparison of personal health beliefs and self-care practices. Scores of personal health beliefs, self-care practices, perceived self-efficacy, perceived threats, and cost-benefit analysis. Sixty- nine PTB patients with a median age of 38, screened during the month of March, 2009, showed a weak positive Pearson's correlational coefficient of (R2=0.177), indicating that personal health beliefs may have some influence on self-care practices. The regression analysis showed an association of 3.1%, thus health beliefs are responsible for self-care undertaken by 3.1 in a 100 PTB patients. Directly Observed Treatment Short Course (DOTS) seems to have reduced the self-care practice of PTS patients. It seems the PTB patient has a potential role to play in the management of his own treatment.

p53 coordinates decidual sestrin 2/AMPK/mTORC1 signaling to govern parturition timing

PubMed Central

Cha, Jeeyeon; Yuan, Jia; Haraguchi, Hirofumi; Bartos, Amanda; Bradshaw, Heather B.; Hirota, Yasushi; Dey, Sudhansu K.

2016-01-01

Inflammation and oxidative stress are known risk factors for preterm birth (PTB); however, the mechanisms and pathways that influence this condition are not fully described. Previously, we showed that mTORC1 signaling is increased in mice harboring a uterine-specific deletion of transformation-related protein 53 (p53d/d mice), which exhibit premature decidual senescence that triggers spontaneous and inflammation-induced PTB. Treatment with the mTORC1 inhibitor rapamycin reduced the incidence of PTB in the p53d/d mice. Decidual senescence with heightened mTORC1 signaling is also a signature of human PTB. Here, we have identified an underlying mechanism for PTB and a potential therapeutic strategy for treating the condition. Treatment of pregnant p53d/d mice with either the antidiabetic drug metformin or the antioxidant resveratrol activated AMPK signaling and inhibited mTORC1 signaling in decidual cells. Both metformin and resveratrol protected against spontaneous and inflammation-induced PTB in p53d/d females. Using multiple approaches, we determined that p53 interacts with sestrins to coordinate an inverse relationship between AMPK and mTORC1 signaling that determines parturition timing. This signature was also observed in human decidual cells. Together, these results reveal that p53-dependent coordination of AMPK and mTORC1 signaling controls parturition timing and suggest that metformin and resveratrol have therapeutic potential to prevent PTB. PMID:27454290

Racism in the form of micro aggressions and the risk of preterm birth among Black women

PubMed Central

Slaughter-Acey, Jaime C.; Sealy-Jefferson, Shawnita; Helmkamp, Laura; Caldwell, Cleopatra H; Osypuk, Theresa L.; Platt, Robert W.; Straughen, Jennifer K.; Dailey-Okezie, Rhonda K.; Abeysekara, Purni; Misra, Dawn P.

2015-01-01

Purpose This study sought to examine whether perceived interpersonal racism in the form of racial micro aggressions was associated with preterm birth (PTB) and whether the presence of depressive symptoms and perceived stress modified the association. Methods Data stem from a cohort of 1410 Black women residing in Metropolitan Detroit, Michigan enrolled into the Life-course Influences on Fetal Environments (LIFE) Study. The Daily Life Experiences of Racism and Bother (DLE-B) scale measured the frequency and perceived stressfulness of racial micro aggressions experienced during the past year. Severe past-week depressive symptomatology was measured by the Centers for Epidemiologic Studies-Depression scale (CES-D) dichotomized at ≥23. Restricted cubic splines were used to model non-linearity between perceived racism and PTB. We used the Perceived Stress Scale (PSS) to assess general stress perceptions. Results Stratified spline regression analysis demonstrated that among those with severe depressive symptoms, perceived racism was not associated with PTB. However, perceived racism was significantly associated with PTB among women with mild to moderate (CES-D score ≤22) depressive symptoms. Perceived racism was not associated with PTB among women with or without high amounts of perceived stress. Conclusions Our findings suggest that racism, at least in the form of racial micro aggressions, may not further impact a group already at high risk for PTB (those with severe depressive symptoms), but may increase the risk of PTB for women at lower baseline risk. PMID:26549132

Racism in the form of micro aggressions and the risk of preterm birth among black women.

PubMed

Slaughter-Acey, Jaime C; Sealy-Jefferson, Shawnita; Helmkamp, Laura; Caldwell, Cleopatra H; Osypuk, Theresa L; Platt, Robert W; Straughen, Jennifer K; Dailey-Okezie, Rhonda K; Abeysekara, Purni; Misra, Dawn P

2016-01-01

This study sought to examine whether perceived interpersonal racism in the form of racial micro aggressions was associated with preterm birth (PTB) and whether the presence of depressive symptoms and perceived stress modified the association. Data stem from a cohort of 1410 black women residing in Metropolitan Detroit, Michigan, enrolled into the Life-course Influences on Fetal Environments (LIFE) study. The Daily Life Experiences of Racism and Bother (DLE-B) scale measured the frequency and perceived stressfulness of racial micro aggressions experienced during the past year. Severe past-week depressive symptomatology was measured by the Centers for Epidemiologic Studies-Depression scale (CES-D) dichotomized at ≥ 23. Restricted cubic splines were used to model nonlinearity between perceived racism and PTB. We used the Perceived Stress Scale to assess general stress perceptions. Stratified spline regression analysis demonstrated that among those with severe depressive symptoms, perceived racism was not associated with PTB. However, perceived racism was significantly associated with PTB among women with mild to moderate (CES-D score ≤ 22) depressive symptoms. Perceived racism was not associated with PTB among women with or without high amounts of perceived stress. Our findings suggest that racism, at least in the form of racial micro aggressions, may not further impact a group already at high risk for PTB (those with severe depressive symptoms), but may increase the risk of PTB for women at lower baseline risk. Copyright © 2016 Elsevier Inc. All rights reserved.

A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism

PubMed Central

Vallström, Anna; Olofsson, Annelie; Öhman, Carina; Rakhimova, Lena; Borén, Thomas; Engstrand, Lars; Brännström, Kristoffer; Arnqvist, Anna

2014-01-01

During persistent infection, optimal expression of bacterial factors is required to match the ever-changing host environment. The gastric pathogen Helicobacter pylori has a large set of simple sequence repeats (SSR), which constitute contingency loci. Through a slipped strand mispairing mechanism, the SSRs generate heterogeneous populations that facilitate adaptation. Here, we present a model that explains, in molecular terms, how an intergenically located T-tract, via slipped strand mispairing, operates with a rheostat-like function, to fine-tune activity of the promoter that drives expression of the sialic acid binding adhesin, SabA. Using T-tract variants, in an isogenic strain background, we show that the length of the T-tract generates multiphasic output from the sabA promoter. Consequently, this alters the H. pylori binding to sialyl-Lewis x receptors on gastric mucosa. Fragment length analysis of post-infection isolated clones shows that the T-tract length is a highly variable feature in H. pylori. This mirrors the host-pathogen interplay, where the bacterium generates a set of clones from which the best-fit phenotypes are selected in the host. In silico and functional in vitro analyzes revealed that the length of the T-tract affects the local DNA structure and thereby binding of the RNA polymerase, through shifting of the axial alignment between the core promoter and UP-like elements. We identified additional genes in H. pylori, with T- or A-tracts positioned similar to that of sabA, and show that variations in the tract length likewise acted as rheostats to modulate cognate promoter output. Thus, we propose that this generally applicable mechanism, mediated by promoter-proximal SSRs, provides an alternative mechanism for transcriptional regulation in bacteria, such as H. pylori, which possesses a limited repertoire of classical trans-acting regulatory factors. PMID:24991812

Sealing Penetrating Eye Injuries Using Photo-Activated Bonding

DTIC Science & Technology

2011-09-01

called PTB ) with the potential to decrease vision loss and ocular complications in warfighters sustaining penetrating eye injuries. Scope: In year 2...not competitive with PTB for sealing is amnion over penetrating cornea injuries, determined that two potential adverse effects (inhibition of...epithelial cell migration and keratocyte phototoxicity) are not significant problems, demonstrated that PTB can be used to seal lacerations in thin (e.g

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2013-10-01

show that the PTB method can provide fixation strengths approaching that of conventional microsurgery and that the PTB repair is unlikely to be...biomaterial during long periods of recovery associated with large nerve deficit reconstruction and long nerve grafts. As with the human amnion nerve...functional recovery model (SFI, sciatic function index) using PTB/xHAM wrap compared to standard (suture) of care microsurgery . Demonstrated improved nerve

Effect of interleukin-6 polymorphism on risk of preterm birth within population strata: a meta-analysis.

PubMed

Wu, Wilfred; Clark, Erin A S; Stoddard, Gregory J; Watkins, W Scott; Esplin, M Sean; Manuck, Tracy A; Xing, Jinchuan; Varner, Michael W; Jorde, Lynn B

2013-04-25

Because of the role of inflammation in preterm birth (PTB), polymorphisms in and near the interleukin-6 gene (IL6) have been association study targets. Several previous studies have assessed the association between PTB and a single nucleotide polymorphism (SNP), rs1800795, located in the IL6 gene promoter region. Their results have been inconsistent and SNP frequencies have varied strikingly among different populations. We therefore conducted a meta-analysis with subgroup analysis by population strata to: (1) reduce the confounding effect of population structure, (2) increase sample size and statistical power, and (3) elucidate the association between rs1800975 and PTB. We reviewed all published papers for PTB phenotype and SNP rs1800795 genotype. Maternal genotype and fetal genotype were analyzed separately and the analyses were stratified by population. The PTB phenotype was defined as gestational age (GA) < 37 weeks, but results from earlier GA were selected when available. All studies were compared by genotype (CC versus CG+GG), based on functional studies.For the maternal genotype analysis, 1,165 PTBs and 3,830 term controls were evaluated. Populations were stratified into women of European descent (for whom the most data were available) and women of heterogeneous origin or admixed populations. All ancestry was self-reported. Women of European descent had a summary odds ratio (OR) of 0.68, (95% confidence interval (CI) 0.51 - 0.91), indicating that the CC genotype is protective against PTB. The result for non-European women was not statistically significant (OR 1.01, 95% CI 0.59 - 1.75). For the fetal genotype analysis, four studies were included; there was no significant association with PTB (OR 0.98, 95% CI 0.72 - 1.33). Sensitivity analysis showed that preterm premature rupture of membrane (PPROM) may be a confounding factor contributing to phenotype heterogeneity. IL6 SNP rs1800795 genotype CC is protective against PTB in women of European descent. It is not significant in other heterogeneous or admixed populations, or in fetal genotype analysis.Population structure is an important confounding factor that should be controlled for in studies of PTB.

Enhancing TB case detection: experience in offering upfront Xpert MTB/RIF testing to pediatric presumptive TB and DR TB cases for early rapid diagnosis of drug sensitive and drug resistant TB.

PubMed

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Nair, Sreenivas Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shayam; Thakur, Rahul; Parmar, Malik; Gray, Christen; Ramachandran, Ranjani; Vadera, Bhavin; Ekka, Shobha; Dhawan, Shikha; Babre, Ameet; Ghedia, Mayank; Alavadi, Umesh; Dewan, Puneet; Khetrapal, Mini; Khanna, Ashwini; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2014-01-01

Diagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India. The study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm. 4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8-13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5-11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2-5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1-99.9), with no statistically significant variation with respect to past history of treatment. Upfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to present-day challenges in the diagnosis of PTB in pediatric patients.

Revisiting the cost-effectiveness of universal cervical length screening: importance of progesterone efficacy.

PubMed

Jain, Siddharth; Kilgore, Meredith; Edwards, Rodney K; Owen, John

2016-07-01

Preterm birth (PTB) is a significant cause of neonatal morbidity and mortality. Studies have shown that vaginal progesterone therapy for women diagnosed with shortened cervical length can reduce the risk of PTB. However, published cost-effectiveness analyses of vaginal progesterone for short cervix have not considered an appropriate range of clinically important parameters. To evaluate the cost-effectiveness of universal cervical length screening in women without a history of spontaneous PTB, assuming that all women with shortened cervical length receive progesterone to reduce the likelihood of PTB. A decision analysis model was developed to compare universal screening and no-screening strategies. The primary outcome was the cost-effectiveness ratio of both the strategies, defined as the estimated patient cost per quality-adjusted life-year (QALY) realized by the children. One-way sensitivity analyses were performed by varying progesterone efficacy to prevent PTB. A probabilistic sensitivity analysis was performed to address uncertainties in model parameter estimates. In our base-case analysis, assuming that progesterone reduces the likelihood of PTB by 11%, the incremental cost-effectiveness ratio for screening was $158,000/QALY. Sensitivity analyses show that these results are highly sensitive to the presumed efficacy of progesterone to prevent PTB. In a 1-way sensitivity analysis, screening results in cost-saving if progesterone can reduce PTB by 36%. Additionally, for screening to be cost-effective at WTP=$60,000 in three clinical scenarios, progesterone therapy has to reduce PTB by 60%, 34% and 93%. Screening is never cost-saving in the worst-case scenario or when serial ultrasounds are employed, but could be cost-saving with a two-day hospitalization only if progesterone were 64% effective. Cervical length screening and treatment with progesterone is a not a dominant, cost-effective strategy unless progesterone is more effective than has been suggested by available data for US women. Until future trials demonstrate greater progesterone efficacy, and effectiveness studies confirm a benefit from screening and treatment, the cost-effectiveness of universal cervical length screening in the United States remains questionable. Copyright © 2016 Elsevier Inc. All rights reserved.

Influenza Pandemics and Tuberculosis Mortality in 1889 and 1918: Analysis of Historical Data from Switzerland.

PubMed

Zürcher, Kathrin; Zwahlen, Marcel; Ballif, Marie; Rieder, Hans L; Egger, Matthias; Fenner, Lukas

2016-01-01

Tuberculosis (TB) mortality declined in the northern hemisphere over the last 200 years, but peaked during the Russian (1889) and the Spanish (1918) influenza pandemics. We studied the impact of these two pandemics on TB mortality. We retrieved historic data from mortality registers for the city of Bern and countrywide for Switzerland. We used Poisson regression models to quantify the excess pulmonary TB (PTB) mortality attributable to influenza. Yearly PTB mortality rates increased during both influenza pandemics. Monthly influenza and PTB mortality rates peaked during winter and early spring. In Bern, for an increase of 100 influenza deaths (per 100,000 population) monthly PTB mortality rates increased by a factor of 1.5 (95%Cl 1.4-1.6, p<0.001) during the Russian, and 3.6 (95%Cl 0.7-18.0, p = 0.13) during the Spanish pandemic. Nationally, the factor was 2.0 (95%Cl 1.8-2.2, p<0.001) and 1.5 (95%Cl 1.1-1.9, p = 0.004), respectively. We did not observe any excess cancer or extrapulmonary TB mortality (as a negative control) during the influenza pandemics. We demonstrate excess PTB mortality during historic influenza pandemics in Switzerland, which supports a role for influenza vaccination in PTB patients in high TB incidence countries.

Prepregnancy body mass index and risk of preterm birth: association heterogeneity by preterm subgroups.

PubMed

Parker, Margaret G; Ouyang, Fengxiu; Pearson, Colleen; Gillman, Matthew W; Belfort, Mandy B; Hong, Xiumei; Wang, Guoying; Heffner, Linda; Zuckerman, Barry; Wang, Xiaobin

2014-04-30

To evaluate the association between prepregnancy body mass index (BMI) is associated with early vs. late and medically-induced vs. spontaneous preterm birth (PTB) subtypes. Using data from the Boston Birth Cohort, we examined associations of prepregnancy BMI with 189 early (<34 completed weeks) and 277 late (34-36 completed weeks) medically-induced PTBs and 320 early and 610 late spontaneous PTBs vs. 3281 term births (37-44 weeks) in multinomial regression. To assess for mediation by important pregnancy complications, we performed sequential models with and without hypertensive disorders of pregnancy, chorioamnionitis, and gestational diabetes. Prevalence of prepregnancy obesity (BMI ≥ 30.0 kg/m2) was 28% among mothers with medically-induced PTBs, 18% among mothers with spontaneous PTBs, and 18% among mothers with term births (p = <0.001). After adjustment for demographic and known risk factors for PTB, prepregnancy obesity was associated with higher odds of both early [OR 1.78 (1.19, 2.66)] and late [OR 1.49 (1.09, 2.04)] medically-induced PTB. These effect estimates were attenuated with inclusion of hypertensive disorders of pregnancy and gestational diabetes. For spontaneous deliveries, prepregnancy obesity was associated with decreased odds of PTB (0.76 [0.58, 0.98]) and underweight was nearly associated with increased odds of PTB (1.46 [0.99, 2.16]). Prepregnancy obesity is associated with higher risk of medically-induced, but not spontaneous PTB. Hypertensive disorders of pregnancy and gestational diabetes appear to partially explain the association between prepregnancy obesity and early and late medically-induced PTB.

Meta-Analysis of Maternal and Fetal Transcriptomic Data Elucidates the Role of Adaptive and Innate Immunity in Preterm Birth

PubMed Central

Vora, Bianca; Wang, Aolin; Kosti, Idit; Huang, Hongtai; Paranjpe, Ishan; Woodruff, Tracey J.; MacKenzie, Tippi; Sirota, Marina

2018-01-01

Preterm birth (PTB) is the leading cause of newborn deaths around the world. Spontaneous preterm birth (sPTB) accounts for two-thirds of all PTBs; however, there remains an unmet need of detecting and preventing sPTB. Although the dysregulation of the immune system has been implicated in various studies, small sizes and irreproducibility of results have limited identification of its role. Here, we present a cross-study meta-analysis to evaluate genome-wide differential gene expression signals in sPTB. A comprehensive search of the NIH genomic database for studies related to sPTB with maternal whole blood samples resulted in data from three separate studies consisting of 339 samples. After aggregating and normalizing these transcriptomic datasets and performing a meta-analysis, we identified 210 genes that were differentially expressed in sPTB relative to term birth. These genes were enriched in immune-related pathways, showing upregulation of innate immunity and downregulation of adaptive immunity in women who delivered preterm. An additional analysis found several of these differentially expressed at mid-gestation, suggesting their potential to be clinically relevant biomarkers. Furthermore, a complementary analysis identified 473 genes differentially expressed in preterm cord blood samples. However, these genes demonstrated downregulation of the innate immune system, a stark contrast to findings using maternal blood samples. These immune-related findings were further confirmed by cell deconvolution as well as upstream transcription and cytokine regulation analyses. Overall, this study identified a strong immune signature related to sPTB as well as several potential biomarkers that could be translated to clinical use.

PRETERM BIRTH AND FUTURE MATERNAL BLOOD PRESSURE, INFLAMMATION AND INTIMAL MEDIAL THICKNESS: THE CARDIA STUDY

PubMed Central

Catov, Janet M; Lewis, Cora E; Lee, Minjae; Wellons, Melissa F; Gunderson, Erica P

2013-01-01

Preterm birth (PTB, <37 weeks) may be a marker of endothelial dysfunction and a pro-inflammatory phenotype; both are risk factors for cardiovascular disease. We studied 916 women (46% Black) with 1,181 live births between enrollment in the Coronary Artery Risk Development in Young Adults (CARDIA) study (age 18-30 years) and 20 years later. C-reactive protein (CRP) was measured at years 7, 15 and 20. Interleukin-6 (IL-6) and carotid intima-media thickness (IMT) which incorporated the common carotid arteries, bifurcations, and internal carotid arteries were measured at year 20. Blood pressure, lipids, anthropometrics, and pregnancy events were assessed at all visits. Change in risk factors and differences in inflammatory markers and IMT according to PTB were evaluated. Women with PTBs (n=226) had higher mean systolic blood pressures (SBP) before pregnancy (106 vs. 105 mmHg, respectively; p=0.03). Systolic and diastolic blood pressure increased more rapidly over 20 years compared to women with term births (p<0.01 time interaction) even after removing women with self-reported hypertension in pregnancy. Women with PTB vs. term births had similar mean IMT adjusted for age, BMI, race, lifestyle and cardiovascular risk factors. CRP and IL-6 did not differ according to PTB. Women with PTB, regardless of hypertension during pregnancy, had higher blood pressure after pregnancy compared to women with term births. In the U.S. where rates of PTB are high and race disparities persist, PTB may identify women with higher blood pressure the years after pregnancy. PMID:23319540

Trending elective preterm deliveries using administrative data.

PubMed

Korst, Lisa M; Fridman, Moshe; Lu, Michael C; Fleege, Laura; Mitchell, Connie; Gregory, Kimberly D

2013-01-01

We propose a methodology for identifying and analysing 'elective' preterm births (PTBs) using administrative data, and apply this methodology to California data with the objective of providing a framework to further explore the potential rationales for early delivery. Using the California linked birth cohorts for 1999, 2002 and 2005, singleton PTBs were identified using birth certificate gestational age ≥ 24 and <37 weeks. Through a hierarchical scheme that first removed cases with standard or 'hard' indications for early delivery (e.g. severe preeclampsia, placenta previa), cases of 'elective' PTB were identified with coding for medical intervention, that is, elective caesarean or labour induction. We calculated rates of elective PTB, with subanalyses of early (<34 weeks of gestational age) and late PTB (34 to <37 weeks of gestational age) using hierarchical logistic regression models. Of 1 387 565 singleton deliveries, 99 614 (7.2%) were preterm. Elective PTBs increased 27.7% over the 6-year study period, with nearly all cases confined to the late PTB stratum; elective late PTB rates rose from 10.5% to 13.5% of all late PTBs (P < 0.0001). Indications for delivery in this Elective Group ('soft indications') included prior pelvic floor repair, mental health conditions, fetal anomalies, malpresentation and oligohydramnios. Six per cent of patients with a late PTB had a medical intervention with no hard or soft indication for delivery. Using administrative data, we developed a method for identifying and trending the proportion of PTBs that is 'elective'. This method can be used to explore and monitor potential strategies for the prevention of elective PTB. © 2012 Blackwell Publishing Ltd.

Role of Maternal Periodontitis in Preterm Birth

PubMed Central

Ren, Hongyu; Du, Minquan

2017-01-01

In the last two decades, many studies have focused on whether periodontitis is a risk factor for preterm birth (PTB). However, both epidemiological investigation and intervention trials have reached contradictory results from different studies. What explains the different findings, and how should future studies be conducted to better assess this risk factor? This article reviews recent epidemiological, animal, and in vitro studies as well as intervention trials that evaluate the link between periodontitis and PTB. Periodontitis may act as a distant reservoir of microbes and inflammatory mediators and contribute to the induction of PTB. Animal studies revealed that maternal infections with periodontal pathogens increase levels of circulating IL-1β, IL-6, IL-8, IL-17, and TNF-α and induce PTB. In vitro models showed that periodontal pathogens/byproducts induce COX-2, IL-8, IFN-γ, and TNF-α secretion and/or apoptosis in placental tissues/cells. The effectiveness of periodontal treatment to prevent PTB is influenced by the diagnostic criteria of periodontitis, microbial community composition, severity of periodontitis, treatment strategy, treatment efficiency, and the period of treatment during pregnancy. Although intervention trials reported contradictory results, oral health maintenance is an important part of preventive care that is both effective and safe throughout pregnancy and should be supported before and during pregnancy. As contradictory epidemiological and intervention studies continue to be published, two new ideas are proposed here: (1) severe and/or generalized periodontitis promotes PTB and (2) periodontitis only promotes PTB for pregnant women who are young or HIV-infected or have preeclampsia, pre-pregnancy obesity, or susceptible genotypes. PMID:28243243

Predicting preterm birth among participants of North Carolina’s Pregnancy Medical Home Program

PubMed Central

Tucker, Christine M.; Berrien, Kate; Menard, M. Kathryn; Herring, Amy H.; Daniels, Julie; Rowley, Diane L.; Halpern, Carolyn Tucker

2016-01-01

Objective To determine which combination of risk factors from Community Care of North Carolina’s (CCNC) Pregnancy Medical Home (PMH) risk screening form was most predictive of preterm birth (PTB) by parity and race/ethnicity. Methods This retrospective cohort included pregnant Medicaid patients screened by the PMH program before 24 weeks gestation who delivered a live birth in North Carolina between September 2011-September 2012 (N=15,428). Data came from CCNC’s Case Management Information System, Medicaid claims, and birth certificates. Logistic regression with backward stepwise elimination was used to arrive at the final models. To internally validate the predictive model, we used bootstrapping techniques. Results The prevalence of PTB was 11%. Multifetal gestation, a previous PTB, cervical insufficiency, diabetes, renal disease, and hypertension were the strongest risk factors with odds ratios ranging from 2.34 to 10.78. Non-Hispanic black race, underweight, smoking during pregnancy, asthma, other chronic conditions, nulliparity, and a history of a low birth weight infant or fetal death/second trimester loss were additional predictors in the final predictive model. About half of the risk factors prioritized by the PMH program remained in our final model (ROC=0.66). The odds of PTB associated with food insecurity and obesity differed by parity. The influence of unsafe or unstable housing and short interpregnancy interval on PTB differed by race/ethnicity. Conclusions Evaluation of the PMH risk screen provides insight to ensure women at highest risk are prioritized for care management. Using multiple data sources, salient risk factors for PTB were identified, allowing for better-targeted approaches for PTB prevention. PMID:26112751

The association between cervical dysplasia, a short cervix, and preterm birth.

PubMed

Miller, Emily S; Sakowicz, Allie; Grobman, William A

2015-10-01

We sought to determine whether cervical dysplasia in the absence of an excisional procedure is associated with an increased risk of preterm birth (PTB) and whether that risk is independent of the presence of a short cervix. This is a cohort study including women with a singleton pregnancy who underwent routine cervical length assessment between 18-23 6/7 weeks of gestation, stratified by cervical dysplasia (ie, no prior dysplasia, prior dysplasia but no excisional procedure, or prior excisional procedure). The frequency of a short cervix (≤2.5 cm) and PTB were compared between groups and multivariable analyses were performed to identify whether: (1) dysplasia alone or a prior excisional procedure was associated with PTB; and (2) whether these factors remained independently associated with PTB after adjusting for the presence of a short cervix. Of the 18,528 women who met inclusion criteria, 3023 (16.3%) had prior dysplasia alone and 1356 (7.3%) had a prior excisional procedure. The frequency of a short cervix for women without dysplasia, with prior dysplasia alone, or with a prior excisional procedure was 0.8%, 1.0%, and 2.2%, respectively (P < .001). The frequency of PTB, respectively, was 6.4%, 6.5%, and 8.4% (P < .001). After adjusting for potential confounding factors, prior excisional procedure but not prior dysplasia alone was associated with PTB. Having a prior cervical excisional procedure but not dysplasia alone is associated with an increased risk of PTB. This association is independent of the presence of a short cervix. Copyright © 2015 Elsevier Inc. All rights reserved.

Trends of preterm birth and low birth weight in Japan: a one hospital-based study.

PubMed

Yorifuji, Takashi; Naruse, Hiroo; Kashima, Saori; Murakoshi, Takeshi; Kato, Tsuguhiko; Inoue, Sachiko; Doi, Hiroyuki; Kawachi, Ichiro

2012-12-26

The proportions of preterm birth (PTB, ie., delivered before 37 gestational weeks) and low birth weight (LBW, ie., birth weight less than 2500 g at delivery) have been rising in developed countries. We sought to examine the factors contributing to the rise in Japan, with particular focus on the effects of obstetric interventions. We used a database maintained by one large regional hospital in Shizuoka, Japan. We restricted the analysis to mothers who delivered live singleton births from 1997 to 2010 (n = 19,221). We assessed the temporal trends in PTB and LBW, then divided the study period into four intervals and compared the proportions of PTB and LBW. We also compared the newborns' outcomes between the intervals. PTB, in particular medically indicated PTB, increased considerably. The increase was largely explained by changes in caesarean sections. The neonatal outcomes did not worsen, and instead the Apgar scores and proportions requiring neonatal intensive care unit (NICU) admission improved. In particular, the risks of NICU admission in the interval from 2007 to 2010 were decreased among all births [odds ratio (OR): 0.84; 95% confidence interval (CI): 0.75, 0.95] and medically indicated births (OR: 0.44; 95% CI: 0.29, 0.68) compared with the interval from 1997 to 2000. Despite the increases in PTB as well as LBW, the present study suggests benefits of obstetric interventions. Rather than simple categorization of PTB or LBW, indicators such as perinatal mortality or other outcomes may be more appropriate for evaluation of perinatal health in developed countries.

Amplitude-Mode Spectroscopy of Charge Excitations in PTB7 π -Conjugated Donor-Acceptor Copolymer for Photovoltaic Applications

NASA Astrophysics Data System (ADS)

Baniya, Sangita; Vardeny, Shai R.; Lafalce, Evan; Peygambarian, Nasser; Vardeny, Z. Valy

2017-06-01

We measure the spectra of resonant Raman scattering and doping-induced absorption of pristine films of the π -conjugated donor-acceptor (D -A ) copolymer, namely, thieno[3,4 b]thiophene-alt-benzodithiophene (PTB7), as well as photoinduced absorption spectrum in a blend of PTB7 with fullerene phenyl-C61-butyric acid methyl ester molecules used for organic photovoltaic (OPV) applications. We find that the D -A copolymer contains six strongly coupled vibrational modes having relatively strong Raman-scattering intensity, which are renormalized upon adding charge polarons onto the copolymer chains either by doping or photogeneration. Since the lower-energy charge-polaron absorption band overlaps with the renormalized vibrational modes, they appear as antiresonance lines superposed onto the induced polaron absorption band in the photoinduced absorption spectrum but less so in the doping-induced absorption spectrum. We show that the Raman-scattering, doping-, and photoinduced absorption spectra of PTB7 are well explained by the amplitude mode model, where a single vibrational propagator describes the renormalized modes and their related intensities in detail. From the relative strengths of the induced infrared activity of the polaron-related vibrations and electronic transitions, we obtain the polaron effective kinetic mass in PTB7 using the amplitude mode model to be approximately 3.8 m* , where m* is the electron effective mass. The enhanced polaronic mass in PTB7 may limit the charge mobility, which, in turn, reduces the OPV solar-cell efficiency based on the PTB7-fullerene blend.

[The role of E. coli adhesiveness in the pathogenesis and clinical course of urinary tract infections].

PubMed

Krzeska, I; Ostojska, J; Dzierzanowska, D

An infection with E. coli is the most frequent cause of the urinary infections in childhood. Virulence depends on several factors out of which a principal role is played by the adhesion of bacteria to the urinary tract epithelium. Such a property have E. coli strains with adherence mannose-positive fimbriae of type P with antigens recognizing and binding glycolipid receptors on epithelial cells in the urinary tract. Children with such infections owe their "sensitivity+" (10% of the population) to genetically determined large number o receptors binding E. coli strains. Incidence and clinical course of the urinary tract infections have been analysed in the group of 184 children. Moreover, sequelae of the urinary tract infections with E. coli have been analysed in dependence on E. coli strain characteristics, i.e. presence or absence of adherent fimbriae from cases of cystitis and significant asymptomatic bacteriuria. Considering pathogenesis of the urinary tract infections as the result of interactions between bacteria and host, antigenic properties of adherent fimbriae might be used for preparation of a vaccine preventing such infections.

Glucose Metabolism Disorder Is Associated with Pulmonary Tuberculosis in Individuals with Respiratory Symptoms from Brazil

PubMed Central

Castro, Simone; Cafezeiro, Aparecida S.; Daltro, Carla; Netto, Eduardo M.; Kornfeld, Hardy; Andrade, Bruno B.

2016-01-01

Background Diabetes mellitus (DM) has been associated with increased risk for pulmonary tuberculosis (PTB) in endemic settings but it is unknown whether PTB risk is also increased by pre-DM. Here, we prospectively examined the association between glucose metabolism disorder (GMD) and PTB in patients with respiratory symptoms at a tuberculosis primary care reference center in Brazil. Methods Oral glucose tolerance test was performed and levels of fasting plasma glucose and glycohemoglobin (HbA1c) were measured in a cohort of 892 individuals presenting with respiratory symptoms of more than two weeks duration. Patients were also tested for PTB with sputum cultures. Prevalence of pre-DM and DM (based on HbA1c) was estimated and tested for association with incident PTB. Other TB risk factors including smoking history were analyzed. Results The majority of the study population (63.1%) exhibited GMD based on HbA1c ≥5.7%. Patients with GMD had higher prevalence of PTB compared to normoglycemic patients. Individuals with DM exhibited increased frequency of TB-related symptoms and detection of acid-fast bacilli in sputum smears. Among patients with previous DM diagnosis, sustained hyperglycemia (HbA1c ≥7.0%) was associated with increased TB prevalence. Smoking history alone was not significantly associated with TB in our study population but the combination of smoking and HbA1c ≥7.0% was associated with 6 times higher odds for PTB. Conclusions Sustained hyperglycemia and pre-DM are independently associated with active PTB. This evidence raises the question whether improving glycemic control in diabetic TB patients would reduce the risk of TB transmission and simultaneously reduce the clinical burden of disease. A better understanding of mechanisms underlying these associations, especially those suggesting that pre-DM may be a factor driving susceptibility to TB is warranted. PMID:27078026

Identification and Quantification of Preterm Birth Biomarkers in Human Cervicovaginal Fluid by Liquid Chromatography/Tandem Mass Spectrometry

PubMed Central

Shah, Sumit J.; Yu, Kenneth H.; Sangar, Vineet; Parry, Samuel I.; Blair, Ian A.

2009-01-01

Spontaneous preterm birth (PTB) before 37 completed weeks of gestation resulting from preterm labor (PTL) is a leading contributor of perinatal morbidity and mortality. Early identification of at-risk women by reliable screening tests could alleviate this health issue; however, conventional methods such as obstetric history and clinical risk factors, uterine activity monitoring, biochemical markers, and cervical sonography for screening women at risk for PTB have proven unsuccessful in lowering the rate of PTB. Cervicovaginal fluid (CVF) might prove to be a useful, readily available biological fluid for identifying diagnostic PTB biomarkers. Human columnar epithelial endocervical-1 (End1) and vaginal (Vk2) cell secretomes were employed to generate a stable isotope labeled proteome (SILAP) standard to facilitate characterization and relative quantification of proteins present in CVF. The SILAP standard was prepared using stable isotope labeling by amino acids in cell culture (SILAC) of End1 and Vk2 through seven passages. The labeled secreted proteins from both cell lines were combined and characterized by liquid-chromatography-tandem mass spectrometry (LC-MS/MS). 1211 proteins were identified in the End1-Vk2 SILAP standard, with 236 proteins being consistently identified in each of the replicates analyzed. Individual proteins were found to contain < 0.5 % of the endogenous unlabeled forms. Identified proteins were screened to provide a set of fifteen candidates that have either previously been identified as potential PTB biomarkers or could be linked mechanistically to PTB. Stable isotope dilution LC-multiple reaction monitoring (MRM/MS) assays were then developed for conducting relative quantification of the fifteen candidate biomarkers in human CVF samples from term and PTB cases. Three proteins were significantly elevated in PTB cases (desmoplakin isoform 1, stratifin, and thrombospondin 1 precursor), providing a foundation for further validation in larger patient cohorts. PMID:19271751

Identification and quantification of preterm birth biomarkers in human cervicovaginal fluid by liquid chromatography/tandem mass spectrometry.

PubMed

Shah, Sumit J; Yu, Kenneth H; Sangar, Vineet; Parry, Samuel I; Blair, Ian A

2009-05-01

Spontaneous preterm birth (PTB) before 37 completed weeks of gestation resulting from preterm labor (PTL) is a leading contributor of perinatal morbidity and mortality. Early identification of at-risk women by reliable screening tests could alleviate this health issue; however, conventional methods such as obstetric history and clinical risk factors, uterine activity monitoring, biochemical markers, and cervical sonography for screening women at risk for PTB have proven unsuccessful in lowering the rate of PTB. Cervicovaginal fluid (CVF) might prove to be a useful, readily available biological fluid for identifying diagnostic PTB biomarkers. Human columnar epithelial endocervical-1 (End1) and vaginal (Vk2) cell secretomes were employed to generate a stable isotope labeled proteome (SILAP) standard to facilitate characterization and relative quantification of proteins present in CVF. The SILAP standard was prepared using stable isotope labeling by amino acids in cell culture (SILAC) of End1 and Vk2 through seven passages. The labeled secreted proteins from both cell lines were combined and characterized by liquid-chromatography-tandem mass spectrometry (LC-MS/MS). In total, 1211 proteins were identified in the End1-Vk2 SILAP standard, with 236 proteins being consistently identified in each of the replicates analyzed. Individual proteins were found to contain <0.5% of the endogenous unlabeled forms. Identified proteins were screened to provide a set of 15 candidates that have either previously been identified as potential PTB biomarkers or could be linked mechanistically to PTB. Stable isotope dilution LC-multiple reaction monitoring (MRM/MS) assays were then developed for conducting relative quantification of the 15 candidate biomarkers in human CVF samples from term and PTB cases. Three proteins were significantly elevated in PTB cases (desmoplakin isoform 1, stratifin, and thrombospondin 1 precursor), providing a foundation for further validation in larger patient cohorts.

The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.

PubMed

Barnard, Dewald A; Irusen, Elvis M; Bruwer, Johannes W; Plekker, Danté; Whitelaw, Andrew C; Deetlefs, Jacobus D; Koegelenberg, Coenraad F N

2015-09-16

Xpert MTB/RIF has been shown to have a superior sensitivity to microscopy for acid fast bacilli (AFB) in sputum and has been recommended as a standard first line investigation for pulmonary tuberculosis (PTB). Bronchoscopy is a valuable tool in diagnosing PTB in sputum negative patients. There is limited data on the utility of Xpert MTB/RIF performed on bronchial lavage specimens. Our aim was to evaluate the diagnostic efficiency of Xpert MTB/RIF performed on bronchial washings in sputum scarce/negative patients with suspected PTB. All patients with a clinical and radiological suspicion of PTB who underwent bronchoscopy between January 2013 and April 2014 were included. The diagnostic efficiencies of Xpert MTB/RIF and microscopy for AFB were compared to culture for Mycobacterium tuberculosis. Thirty nine of 112 patients were diagnosed with culture-positive PTB. Xpert MTB/RIF was positive in 36/39 with a sensitivity of 92.3% (95% CI 78-98%) for PTB, which was superior to that of smear microscopy (41%; 95% CI 26.0-57.8%, p = 0.005). The specificities of Xpert MTB/RIF and smear microscopy were 87.7% (95% CI 77.4-93.9%) and 98.6% (95% CI 91.6%-99.9%) respectively. Xpert MTB/RIF had a positive predictive value of 80% (95% CI; 65-89.9%) and negative predictive value of 95.5% (95% CI 86.6-98.8%). 3/9 patients with Xpert MTB/RIF positive culture negative results were treated for PTB based on clinical and radiological findings. Xpert MTB/RIF has a higher sensitivity than smear microscopy and similar specificity for the immediate confirmation of PTB in specimens obtained by bronchial washing, and should be utilised in patients with a high suspicion of pulmonary tuberculosis.

Co-endemicity of Pulmonary Tuberculosis and Intestinal Helminth Infection in the People’s Republic of China

PubMed Central

Li, Xin-Xu; Ren, Zhou-Peng; Wang, Li-Xia; Zhang, Hui; Jiang, Shi-Wen; Chen, Jia-Xu; Wang, Jin-Feng; Zhou, Xiao-Nong

2016-01-01

Both pulmonary tuberculosis (PTB) and intestinal helminth infection (IHI) affect millions of individuals every year in China. However, the national-scale estimation of prevalence predictors and prevalence maps for these diseases, as well as co-endemic relative risk (RR) maps of both diseases’ prevalence are not well developed. There are co-endemic, high prevalence areas of both diseases, whose delimitation is essential for devising effective control strategies. Bayesian geostatistical logistic regression models including socio-economic, climatic, geographical and environmental predictors were fitted separately for active PTB and IHI based on data from the national surveys for PTB and major human parasitic diseases that were completed in 2010 and 2004, respectively. Prevalence maps and co-endemic RR maps were constructed for both diseases by means of Bayesian Kriging model and Bayesian shared component model capable of appraising the fraction of variance of spatial RRs shared by both diseases, and those specific for each one, under an assumption that there are unobserved covariates common to both diseases. Our results indicate that gross domestic product (GDP) per capita had a negative association, while rural regions, the arid and polar zones and elevation had positive association with active PTB prevalence; for the IHI prevalence, GDP per capita and distance to water bodies had a negative association, the equatorial and warm zones and the normalized difference vegetation index had a positive association. Moderate to high prevalence of active PTB and low prevalence of IHI were predicted in western regions, low to moderate prevalence of active PTB and low prevalence of IHI were predicted in north-central regions and the southeast coastal regions, and moderate to high prevalence of active PTB and high prevalence of IHI were predicted in the south-western regions. Thus, co-endemic areas of active PTB and IHI were located in the south-western regions of China, which might be determined by socio-economic factors, such as GDP per capita. PMID:27088504

Exposure to fine particulate matter during pregnancy and risk of preterm birth among women in New Jersey, Ohio, and Pennsylvania, 2000-2005.

PubMed

Rappazzo, Kristen M; Daniels, Julie L; Messer, Lynne C; Poole, Charles; Lobdell, Danelle T

2014-09-01

Particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) has been variably associated with preterm birth (PTB). We classified PTB into four categories (20-27, 28-31, 32-34, and 35-36 weeks completed gestation) and estimated risk differences (RDs) for each category in association with a 1-μg/m3 increase in PM2.5 exposure during each week of gestation. We assembled a cohort of singleton pregnancies that completed ≥ 20 weeks of gestation during 2000-2005 using live birth certificate data from three states (Pennsylvania, Ohio, and New Jersey) (n = 1,940,213; 8% PTB). We estimated mean PM2.5 exposures for each week of gestation from monitor-corrected Community Multi-Scale Air Quality modeling data. RDs were estimated using modified Poisson linear regression and adjusted for maternal race/ethnicity, marital status, education, age, and ozone. RD estimates varied by exposure window and outcome period. Average PM2.5 exposure during the fourth week of gestation was positively associated with all PTB outcomes, although magnitude varied by PTB category [e.g., for a 1-μg/m3 increase, RD = 11.8 (95% CI: -6, 29.2); RD = 46 (95% CI: 23.2, 68.9); RD = 61.1 (95% CI: 22.6, 99.7); and RD = 28.5 (95% CI: -39, 95.7) for preterm births during 20-27, 28-31, 32-34, and 35-36 weeks, respectively]. Exposures during the week of birth and the 2 weeks before birth also were positively associated with all PTB categories. Exposures beginning around the time of implantation and near birth appeared to be more strongly associated with PTB than exposures during other time periods. Because particulate matter exposure is ubiquitous, evidence of effects of PM2.5 exposure on PTB, even if small in magnitude, is cause for concern.

Source and Extent of Volcanic Ashes at the Permian-Triassic Boundary in South China and Its implications

NASA Astrophysics Data System (ADS)

Wang, M.; Zhong, Y. T.; Hou, Y. L.; He, B.

2017-12-01

Highly correlated with the Permian-Triassic Boundary (PTB) Mass Extinction in stratigraphic section, volcanic ashes around the P-T Boundary in South China have been suggested to be a likely cause of the PTB Mass Extinction. So the nature, source and extent of these volcanic ashes have great significance in figuring out the cause of the PTB Mass Extinction. In this study, we attempt to constrain the source and extent of the PTB volcanic ashes in South China by studying pyroclastic sedimentary rocks and the spatial distribution of tuffs and ashes in South China. The detrital zircons of tuffaceous sandstones from Penglaitan section yield an age spectrum peaked at 252Ma, with ɛHf(t) values varying from -20 to -5 ,and have Nb/Hf, Th/Nb and Hf/Th ratios similar to those from arc/orogenic-related settings. Coarse tuffaceous sandstones imply that their source is in limited distance. Those pyroclastic sedimentary rocks in Penglaitan are well correlated with the PTB volcanic ashes in Meishan GSSP section in stratigraphy. In the spatial distribution, pyroclastic sedimentary rocks and tuffs distribute only in southwest of South China, while finer volcanic ashes are mainly in the northern part. This spatial distribution suggests the source of tuffs and ashes was to the south or southwest of South China. Former studies especially that of Permian-Triassic magmatism in Hainan Island have supported the existence of a continental arc related to the subduction and closure of Palaeo-Tethys on the southwestern margin of South China during Permian to early Triassic. It is suggested that the PTB ashes possibly derived from this Paleo-Tethys continental arc. The fact that volcanic ashes haven't been reported or found in PTB stratum in North China or Northwest China implies a limited extent of the volcanism, which thus is too small to cause the PTB mass extinction.

Identification of the SRC pyrimidine-binding protein (SPy) as hnRNP K: implications in the regulation of SRC1A transcription

PubMed Central

Ritchie, Shawn A.; Pasha, Mohammed K.; Batten, Danielle J. P.; Sharma, Rajendra K.; Olson, Douglas J. H.; Ross, Andrew R. S.; Bonham, Keith

2003-01-01

The human SRC gene encodes pp60c–src, a non-receptor tyrosine kinase involved in numerous signaling pathways. Activation or overexpression of c-Src has also been linked to a number of important human cancers. Transcription of the SRC gene is complex and regulated by two closely linked but highly dissimilar promoters, each associated with its own distinct non-coding exon. In many tissues SRC expression is regulated by the housekeeping-like SRC1A promoter. In addition to other regulatory elements, three substantial polypurine:polypyrimidine (TC) tracts within this promoter are required for full transcriptional activity. Previously, we described an unusual factor called SRC pyrimidine-binding protein (SPy) that could bind to two of these TC tracts in their double-stranded form, but was also capable of interacting with higher affinity to all three pyrimidine tracts in their single-stranded form. Mutations in the TC tracts, which abolished the ability of SPy to interact with its double-stranded DNA target, significantly reduced SRC1A promoter activity, especially in concert with mutations in critical Sp1 binding sites. Here we expand upon our characterization of this interesting factor and describe the purification of SPy from human SW620 colon cancer cells using a DNA affinity-based approach. Subsequent in-gel tryptic digestion of purified SPy followed by MALDI-TOF mass spectrometric analysis identified SPy as heterogeneous nuclear ribonucleoprotein K (hnRNP K), a known nucleic-acid binding protein implicated in various aspects of gene expression including transcription. These data provide new insights into the double- and single-stranded DNA-binding specificity, as well as functional properties of hnRNP K, and suggest that hnRNP K is a critical component of SRC1A transcriptional processes. PMID:12595559

Inhibition of experimental ascending urinary tract infection by an epithelial cell-surface receptor analogue

NASA Astrophysics Data System (ADS)

Edén, C. Svanborg; Freter, R.; Hagberg, L.; Hull, R.; Hull, S.; Leffler, H.; Schoolnik, G.

1982-08-01

It has been shown that the establishment of urinary tract infection by Escherichia coli is dependent on attachment of the bacteria to epithelial cells1-4. The attachment involves specific epithelial cell receptors, which have been characterized as glycolipids5-10. Reversible binding to cell-surface mannosides may also be important4,11-13. This suggests an approach to the treatment of infections-that of blocking bacterial attachment with cell membrane receptor analogues. Using E. coli mutants lacking one or other of the two binding specificities (glycolipid and mannose), we show here that glycolipid analogues can block in vitro adhesion and in vivo urinary tract infection.

Characteristics and risk factors of preterm births in a tertiary center in Lagos, Nigeria.

PubMed

Butali, Azeez; Ezeaka, Chinyere; Ekhaguere, Osayame; Weathers, Nancy; Ladd, Jenna; Fajolu, Iretiola; Esezobor, Christopher; Makwe, Christian; Odusanya, Bukola; Anorlu, Rose; Adeyemo, Wasiu; Iroha, Edna; Egri-Okwaji, Mathias; Adejumo, Prisca; Oyeneyin, Lawal; Abiodun, Moses; Badejoko, Bolaji; Ryckman, Kelli

2016-01-01

Preterm birth is a dire complication of pregnancy that poses huge long-term medical and financial burdens for affected children, their families, and the health care system. The aim of the present study was to identify characteristics associated with preterm births at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria from 2011 to 2013. We obtained Information from 5,561 maternal, fetal/neonatal and obstetric records from the labor ward. We excluded delivery at less than 22 weeks (0.25%), post-term birth at ≥42 weeks gestation (1.3%), and unknown gestation (1.4%). Additionally, we excluded records of multiple births (5.4%) and stillbirths (8.3%) leaving 4,691 records of singleton live-births for analysis. Logistic regression analysis was performed comparing preterm birth (22-36 weeks gestation) to term birth (37-41 weeks gestation). Multiple variable models adjusting for maternal age, parity, fetal position, delivery method and booking status were also evaluated. Multinomial regression was used to identify characteristics associated with preterm birth (PTB) defined as early PTB (22-31 weeks gestation), moderate PTB (32-34 weeks gestation), late PTB (35-36 weeks gestation), compared to term birth (37-41 completed weeks gestation). From our data, 16.8% of the singleton live-birth deliveries were preterm (<37 weeks gestation). Of these, 4.7% were early (22-31 weeks), 4.5% were moderate (32-34 weeks) and 7.7% were late (35-36) PTBs. Older maternal age (≥35 years) [odds ratio (OR) = 1.41], hypertension (OR = 3.44) and rupture of membranes (OR = 4.03) were significantly associated with increased odds of PTB. Women being treated for the prevention of mother-to-child transmission of HIV were at a significantly decreased risk for PTB (OR = 0.70). Sixteen percent of women in this cohort were not registered for antenatal care in LUTH. These non-registered subjects had significantly greater odds of all categories of PTB, including early (odds ratio (OR) = 20.8), moderate (OR = 8.68), and late (OR = 2.15). PTB and risks for PTB remain high in Nigeria. We recommend that any high risk pregnancy should be referred to a tertiary center for prenatal care in order to significantly reduce adverse birth outcomes such as PTBs.

Characteristics and risk factors of preterm births in a tertiary center in Lagos, Nigeria

PubMed Central

Butali, Azeez; Ezeaka, Chinyere; Ekhaguere, Osayame; Weathers, Nancy; Ladd, Jenna; Fajolu, Iretiola; Esezobor, Christopher; Makwe, Christian; Odusanya, Bukola; Anorlu, Rose; Adeyemo, Wasiu; Iroha, Edna; Egri-Okwaji, Mathias; Adejumo, Prisca; Oyeneyin, Lawal; Abiodun, Moses; Badejoko, Bolaji; Ryckman, Kelli

2016-01-01

Introduction Preterm birth is a dire complication of pregnancy that poses huge long-term medical and financial burdens for affected children, their families, and the health care system. The aim of the present study was to identify characteristics associated with preterm births at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria from 2011 to 2013. Methods We obtained Information from 5,561 maternal, fetal/neonatal and obstetric records from the labor ward. We excluded delivery at less than 22 weeks (0.25%), post-term birth at ≥42 weeks gestation (1.3%), and unknown gestation (1.4%). Additionally, we excluded records of multiple births (5.4%) and stillbirths (8.3%) leaving 4,691 records of singleton live-births for analysis. Logistic regression analysis was performed comparing preterm birth (22-36 weeks gestation) to term birth (37-41 weeks gestation). Multiple variable models adjusting for maternal age, parity, fetal position, delivery method and booking status were also evaluated. Multinomial regression was used to identify characteristics associated with preterm birth (PTB) defined as early PTB (22-31 weeks gestation), moderate PTB (32-34 weeks gestation), late PTB (35-36 weeks gestation), compared to term birth (37-41 completed weeks gestation). Results From our data, 16.8% of the singleton live-birth deliveries were preterm (<37 weeks gestation). Of these, 4.7% were early (22-31 weeks), 4.5% were moderate (32-34 weeks) and 7.7% were late (35-36) PTBs. Older maternal age (≥35 years) [odds ratio (OR) = 1.41], hypertension (OR = 3.44) and rupture of membranes (OR = 4.03) were significantly associated with increased odds of PTB. Women being treated for the prevention of mother-to-child transmission of HIV were at a significantly decreased risk for PTB (OR = 0.70). Sixteen percent of women in this cohort were not registered for antenatal care in LUTH. These non-registered subjects had significantly greater odds of all categories of PTB, including early (odds ratio (OR) = 20.8), moderate (OR = 8.68), and late (OR = 2.15). Conclusion PTB and risks for PTB remain high in Nigeria. We recommend that any high risk pregnancy should be referred to a tertiary center for prenatal care in order to significantly reduce adverse birth outcomes such as PTBs. PMID:27583065

Intestinal Parasite Co-infection among Pulmonary Tuberculosis Cases without Human Immunodeficiency Virus Infection in a Rural County in China

PubMed Central

Li, Xin-Xu; Chen, Jia-Xu; Wang, Li-Xia; Tian, Li-Guang; Zhang, Yu-Ping; Dong, Shuang-Pin; Hu, Xue-Guang; Liu, Jian; Wang, Feng-Feng; Wang, Yue; Yin, Xiao-Mei; He, Li-Jun; Yan, Qiu-Ye; Zhang, Hong-Wei; Xu, Bian-Li; Zhou, Xiao-Nong

2014-01-01

Epidemiologic studies of co-infection with tuberculosis (TB) and intestinal parasites in humans have not been extensively investigated in China. A cross-section study was conducted in a rural county of Henan Province, China. Pulmonary TB (PTB) case-patients receiving treatment for infection with Mycobacterium tuberculosis and healthy controls matched for geographic area, age, and sex were surveyed by using questionnaires. Fecal and blood specimens were collected for detection of intestinal parasites, routine blood examination, and infection with human immunodeficiency virus. The chi-square test was used for univariate analysis and multivariate logistic regression models were used to adjust for potential confounding factors. A total of 369 persons with PTB and 366 healthy controls were included; all participants were negative for human immunodeficiency virus. The overall prevalence of intestinal parasites in persons with PTB was 14.9%, including intestinal protozoa (7.9%) and helminthes (7.6%). The infection spectrum of intestinal parasites was Entamoeba spp. (1.4%), Blastocystis hominis (6.2%), Trichomonas hominis (0.3%), Clonorchis sinensis (0.3%), Ascaris lumbricoides (0.5%), Trichuris trichiura (2.2%), and hookworm (4.6%). The prevalence of intestinal parasites showed no significant difference between persons with PTB and healthy controls after adjusting for potential confounding factors. There was no factor that affected infection rates for intestinal parasites between the two groups. Infection with intestinal parasites of persons with PTB was associated with female sex (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [CI] = 1.01–4.17), body mass index ≤ 19 (AOR = 3.02, 95% CI = 1.47–6.20), and anemia (AOR = 2.43, 95% CI = 1.17–5.03). Infection of healthy controls was only associated with an annual labor time in farmlands > 2 months (AOR = 4.50, 95% CI = 2.03–10.00). In addition, there was no significant trend between rates of infection with intestinal parasites and duration of receiving treatment for infection with M. tuberculosis in persons with PTB. The prevalence of intestinal parasites was not higher in persons with PTB, and there was no evidence that PTB increased susceptibility to intestinal parasites in this study. However, for patients with PTB, women and patients with comorbidities were more likely to be infected with intestinal parasites. PMID:24166044

Omega-3 supplementation to prevent recurrent preterm birth: a systematic review and metaanalysis of randomized controlled trials.

PubMed

Saccone, Gabriele; Berghella, Vincenzo

2015-08-01

The purpose of this study was to evaluate the efficacy of omega-3 supplementation for the prevention of recurrent preterm birth (PTB) in asymptomatic singleton gestations with previous PTB. We searched fish oil, long chain polyunsaturated fatty acids, pregnancy, and omega-3 in MEDLINE, OVID, Scopus, ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, and the Cochrane Central Register of Controlled Trials from inception of each database to December 2014 with no limit for language. In addition the reference lists of all identified articles were examined to identify studies that were not captured by electronic searches. We performed a metaanalysis of randomized controlled trials of asymptomatic singleton gestations with previous PTB who were assigned randomly to prophylactic omega-3 supplementation vs control (either placebo or no treatment). The primary outcome was predefined as PTB at <37 weeks of gestation. The pooled results were reported as relative risk (RR) with 95% confidence interval (95% CI). The protocol of this review was registered with PROSPERO (registration number: CRD42015016371). Two randomized controlled trials that included 1080 women were analyzed. The mean gestational age at randomization was approximately 134 days in both groups (mean difference, 0.01 days; 95% CI, -0.13 to 0.14). Women who received omega-3 had similar rates of PTB at <37 weeks of gestation (34.5% vs 39.8%; RR, 0.81; 95% CI, 0.59-1.12) and PTB at <34 weeks of gestation (12.0% vs 15.4%; RR, 0.62; 95% CI, 0.26-1.46) compared with control subjects. The omega-3 groups had a statistically significantly longer latency (mean difference, 2.10 days; 95% CI, 1.98-2.22) and higher birthweight (mean difference, 102.52 g; 95% CI, 20.09-184.95) compared with control subjects; the other secondary outcomes (which included gestational age at delivery, spontaneous PTB at <37 and 34 weeks of gestation, admission to the intensive care unit, intraventricular hemorrhage, necrotizing enterocolitis, sepsis, and perinatal death) were similar. Omega-3 supplementation during pregnancy does not prevent recurrent PTB in asymptomatic singleton gestations with previous PTB. The benefits in longer latency and higher birth weight may deserve further study. Copyright © 2015 Elsevier Inc. All rights reserved.

Vitamin D status among pulmonary TB patients and non-TB controls: a cross-sectional study from Mwanza, Tanzania.

PubMed

Friis, Henrik; Range, Nyagosya; Changalucha, John; Praygod, George; Jeremiah, Kidola; Faurholt-Jepsen, Daniel; Krarup, Henrik; Mølgaard, Christian; Andersen, Åse Bengaard

2013-01-01

Little is known about vitamin D status in low-income populations burdened with infectious diseases. Hence, there is a need for data on correlates of serum 25-hydroxy vitamin D (S-25(OH)D) and its validity during infections. To assess the role of pulmonary TB (PTB) and HIV as correlates of S-25(OH)D. Age-sex-matched cross-sectional study among PTB patients and non-TB controls. PTB patients were categorized as sputum negative (PTB-) and positive (PTB+) by culture. Non-TB controls were randomly selected among age-sex-matched neighbours to PTB+ patients. Height, weight, arm circumference and triceps skinfold were measured, and body mass index (BMI), arm fat (AFA) and muscle area (AMA) computed. HIV status, and S-25(OH)D, C-reactive protein (S-CRP) and α1-acid glycoprotein (S-AGP) were determined. Linear regression analysis with controls and PTB patients combined was used to identify correlates of S-25(OH)D. S-25(OH)D data were available on 97.8% (1570) of 1605 participants. Mean (SD) S-25(OH)D was 84.4 (25.6) nmol/L with 39.6% <75 nmol/L among 347 non-TB controls. Time of recruitment, sex, PTB and HIV, and elevated S-AGP were correlates of S-25(OH)D. S-25(OH)D was 24.8 (95% CI 18.6;30.9) nmol/L higher in PTB compared to controls among females, but only 9.8 (95% CI:4.5;15.2) nmol/L among males (interaction p<0.0001). Females had 13.8 (95% CI:8.2;21.9) nmol/L lower S-25(OH)D than males, and HIV infected individuals had 8.5 (95% CI:4.9;12.1) higher S-25(OH)D compared to uninfected. Elevated S-AGP was a positive correlate of S-25(OH)D. Low BMI was associated with S-25(OH)D, but not with infections or S-AGP in the model. While S-25(OH)D may decline transiently during a mild acute phase response, it may increase if the acute phase response leads to loss of fat. The validity of S-25(OH)D as a marker of vitamin D status may be affected by infections.

Decomposition Analysis of Black-White Disparities in Birth Outcomes: The Relative Contribution of Air Pollution and Social Factors in California.

PubMed

Benmarhnia, Tarik; Huang, Jonathan; Basu, Rupa; Wu, Jun; Bruckner, Tim A

2017-10-04

Racial/ethnic disparities in preterm birth (PTB) are well documented in the epidemiological literature, but little is known about the relative contribution of different social and environmental determinants of such disparities in birth outcome. Furthermore, increased focus has recently turned toward modifiable aspects of the environment, including physical characteristics, such as neighborhood air pollution, to reduce disparities in birth outcomes. To apply decomposition methods to understand disparities in preterm birth (PTB) prevalence between births of non-Hispanic black individuals and births of non-Hispanic white individuals in California, according to individual demographics, neighborhood socioeconomic environment, and neighborhood air pollution. We used all live singleton births in California spanning 2005 to 2010 and estimated PTBs and other adverse birth outcomes for infants borne by non-Hispanic black mothers and white mothers. To compare individual-level, neighborhood-level, and air pollution [Particulate Matter, 2.5 micrometers or less (PM 2.5 ) and nitrogen dioxide (NO 2 )] predictors, we conducted a nonlinear extension of the Blinder-Oaxaca method to decompose racial/ethnic disparities in PTB. The predicted differences in probability of PTB between black and white infants was 0.056 (95% CI: 0.054, 0.058). All included predictors explained 37.8% of the black-white disparity. Overall, individual (17.5% for PTB) and neighborhood-level variables (16.1% for PTB) explained a greater proportion of the black-white difference in birth outcomes than air pollution (5.7% for PTB). Our results suggest that, although the role of individual and neighborhood factors remains prevailing in explaining black-white differences in birth outcomes, the individual contribution of PM 2.5 is comparable in magnitude to any single individual- or neighborhood-level factor. https://doi.org/10.1289/EHP490.

Prepregnancy body mass index and risk of preterm birth: association heterogeneity by preterm subgroups

PubMed Central

2014-01-01

Background To evaluate the association between prepregnancy body mass index (BMI) is associated with early vs. late and medically-induced vs. spontaneous preterm birth (PTB) subtypes. Methods Using data from the Boston Birth Cohort, we examined associations of prepregnancy BMI with 189 early (<34 completed weeks) and 277 late (34–36 completed weeks) medically-induced PTBs and 320 early and 610 late spontaneous PTBs vs. 3281 term births (37–44 weeks) in multinomial regression. To assess for mediation by important pregnancy complications, we performed sequential models with and without hypertensive disorders of pregnancy, chorioamnionitis, and gestational diabetes. Results Prevalence of prepregnancy obesity (BMI ≥ 30.0 kg/m2) was 28% among mothers with medically-induced PTBs, 18% among mothers with spontaneous PTBs, and 18% among mothers with term births (p = <0.001). After adjustment for demographic and known risk factors for PTB, prepregnancy obesity was associated with higher odds of both early [OR 1.78 (1.19, 2.66)] and late [OR 1.49 (1.09, 2.04)] medically-induced PTB. These effect estimates were attenuated with inclusion of hypertensive disorders of pregnancy and gestational diabetes. For spontaneous deliveries, prepregnancy obesity was associated with decreased odds of PTB (0.76 [0.58, 0.98]) and underweight was nearly associated with increased odds of PTB (1.46 [0.99, 2.16]). Conclusion Prepregnancy obesity is associated with higher risk of medically-induced, but not spontaneous PTB. Hypertensive disorders of pregnancy and gestational diabetes appear to partially explain the association between prepregnancy obesity and early and late medically-induced PTB. PMID:24779674

Preterm birth with placental evidence of malperfusion is associated with cardiovascular risk factors after pregnancy: a prospective cohort study.

PubMed

Catov, J M; Muldoon, M F; Reis, S E; Ness, R B; Nguyen, L N; Yamal, J-M; Hwang, H; Parks, W T

2017-11-28

Preterm birth (PTB) is associated with excess maternal cardiovascular disease risk. We considered that women with PTB and placental evidence of maternal malperfusion would be particularly affected. Pregnancy cohort study. Pittsburgh, PA, USA. Women with PTB (n = 115) and term births (n = 210) evaluated 4-12 years after pregnancy. Cardiometabolic risk markers were compared in women with prior PTB versus term births; pre-eclampsia and growth restriction cases were excluded. Placental evidence of maternal vascular malperfusion (vasculopathy, infarct, advanced villous maturation, perivillous fibrin, intervillous fibrin deposition), acute infection/inflammation (chorioamnionitis, funisitis, deciduitus) and villitis of unknown aetiology (chronic inflammation) was used to classify PTBs. Carotid artery intima-media thickness (IMT), fasting lipids, blood pressure (BP) and inflammatory markers measured after delivery. Women with PTB and malperfusion lesions had higher total cholesterol (+13.5 mg/dl) and systolic BP (+4.0 mmHg) at follow up compared with women with term births, accounting for age, race, pre-pregnancy BMI, and smoking (P < 0.05). Women with PTB and malperfusion accompanied by inflammatory lesions had the most atherogenic profile after pregnancy (cholesterol +18.7, apolipoprotein B + 12.7 mg/dl; all P < 0.05), adjusted for pre-pregnancy features. Carotid IMT was higher in this group (+0.037 cm, P = 0.031) accounting for pre-pregnancy factors; differences were attenuated after adjusting for BP and atherogenic lipids at follow up (+0.027, P = 0.095). PTBs with placental malperfusion were associated with an excess maternal cardiometabolic risk burden in the decade after pregnancy. The placenta may offer insight into subtypes of PTB related to maternal cardiovascular disease. Preterm births with placental malperfusion may mark women at higher cardiovascular disease risk. © 2017 Royal College of Obstetricians and Gynaecologists.

Preterm birth among the Hmong, other Asian subgroups and non-Hispanic whites in California.

PubMed

Vang, Zoua M; Elo, Irma T; Nagano, Makoto

2015-08-21

We investigated very preterm (VPTB) and preterm birth (PTB) risk among Hmong women relative to non-Hispanic whites and other Asian subgroups. We also examined the maternal education health gradient across subgroups. California birth record data (2002-2004) were used to analyze 568,652 singleton births to white and Asian women. Pearson Chi-square and logistic regression were used to assess variation in maternal characteristics and VPTB/PTB risk by subgroup. White, Chinese, Japanese, Korean, Asian Indian, and Vietnamese women had 36-59% lower odds of VPTB and 30-56% lower odds of PTB than Hmong women. Controls for covariates did not substantially diminish these disparities. Cambodian, Filipino and Lao/Thai women's odds of VPTB were similar to that of Hmong women. But they had higher adjusted odds of PTB compared to the Hmong. There was heterogeneity in the educational gradient of PTB, with significant differences between the least and most educated women among whites, Chinese, Japanese, Asian Indians, Cambodians, and Laoians/Thais. Maternal education was not associated with PTB for Hmong, Vietnamese and Korean women, however. Studies of Hmong infant health from the 1980s, the decade immediately following the group's mass migration to the US, found no significant differences in adverse birth outcomes between Hmong and white women. By the early 2000s, however, the disparities in VPTB and PTB between Hmong and white women, as well as between Hmong and other Asian women had become substantial. Moreover, despite gains in post-secondary education among childbearing-age Hmong women, the returns to education for the Hmong are negligible. Higher educational attainment does not confer the same health benefits for Hmong women as it does for whites and other Asian subgroups.

Mortality trends and risk of dying from pulmonary tuberculosis in the 7 socioeconomic regions and the 32 States of Mexico, 2000-2009.

PubMed

Sánchez-Barriga, Juan Jesús

2015-01-01

Tuberculosis (TB) is a world public health problem that still has a high morbidity and mortality rate mainly in countries with significant wealth gaps. Poverty, malnutrition, HIV infection, drug resistance, diabetes and addictions (mainly alcoholism) have been seen to contribute to the persistence of TB as an important health problem in Mexico. Death certificates associated with pulmonary tuberculosis (PTB) for 2000-2009 were obtained from the National Information System of the Secretariat of Health. Rates of mortality nationwide, by state, and by socioeconomic region were calculated. The strength of association between states where individuals resided, socioeconomic regions, and education with mortality from PTB was determined. Age-adjusted mortality rates per 100,000 inhabitants who died from PTB decreased from 4.1 to 2 between 2000 and 2009. Men (67.7%) presented higher mortality than women (32.3%). Individuals failing to complete elementary education presented a higher risk of dying from PTB (RR 1.08 [95%CI: 1.05-1.12]). The socioeconomic region and the entities with the strongest association were region 1, 5, Chiapas and Baja California. Region 1 in 2007 presented RR 7.34 (95%CI: 5.32-10.13), and region 5 in 2009 had RR 10.08 (95%CI: 6.83-14.88). In Mexico, the annual mortality rate from PTB decreased. Men presented higher mortality than women. Individuals failing to complete elementary education showed a higher risk of dying from PTB. The states and regions of Mexico that presented a stronger association with mortality from PTB were Chiapas and Baja California, region 1 and 5. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Estimated number of preterm births and low birth weight children born in the United States due to maternal binge drinking.

PubMed

Truong, Khoa D; Reifsnider, Odette S; Mayorga, Maria E; Spitler, Hugh

2013-05-01

The objective of this study was to estimate the aggregate burden of maternal binge drinking on preterm birth (PTB) and low birth weight (LBW) across American sociodemographic groups in 2008. To estimate the aggregate burden of maternal binge drinking on preterm birth (PTB) and low birth weight (LBW) across American sociodemographic groups in 2008. A simulation model was developed to estimate the number of PTB and LBW cases due to maternal binge drinking. Data inputs for the model included number of births and rates of preterm and LBW from the National Center for Health Statistics; female population by childbearing age groups from the U.S. Census; increased relative risks of preterm and LBW deliveries due to maternal binge drinking extracted from the literature; and adjusted prevalence of binge drinking among pregnant women estimated in a multivariate logistic regression model using Behavioral Risk Factor Surveillance System survey. The most conservative estimates attributed maternal binge drinking to 8,701 (95% CI: 7,804-9,598) PTBs (1.75% of all PTBs) and 5,627 (95% CI 5,121-6,133) LBW deliveries in 2008, with 3,708 (95% CI: 3,375-4,041) cases of both PTB and LBW. The estimated rate of PTB due to maternal binge drinking was 1.57% among all PTBs to White women, 0.69% among Black women, 3.31% among Hispanic women, and 2.35% among other races. Compared to other age groups, women ages 40-44 had the highest adjusted binge drinking rate and highest PTB rate due to maternal binge drinking (4.33%). Maternal binge drinking contributed significantly to PTB and LBW differentially across sociodemographic groups.

Maternal mercury exposure, season of conception and adverse birth outcomes in an urban immigrant community in Brooklyn, New York, U.S.A.

PubMed

Bashore, Cynthia J; Geer, Laura A; He, Xin; Puett, Robin; Parsons, Patrick J; Palmer, Christopher D; Steuerwald, Amy J; Abulafia, Ovadia; Dalloul, Mudar; Sapkota, Amir

2014-08-18

Adverse birth outcomes including preterm birth (PTB: <37 weeks gestation) and low birth weight (LBW: <2500 g) can result in severe infant morbidity and mortality. In the United States, there are racial and ethnic differences in the prevalence of PTB and LBW. We investigated the association between PTB and LBW with prenatal mercury (Hg) exposure and season of conception in an urban immigrant community in Brooklyn, New York. We recruited 191 pregnant women aged 18-45 in a Brooklyn Prenatal Clinic and followed them until delivery. Urine specimens were collected from the participants during the 6th to 9th month of pregnancy. Cord blood specimens and neonate anthropometric data were collected at birth. We used multivariate logistic regression models to investigate the odds of LBW or PTB with either maternal urinary mercury or neonate cord blood mercury. We used linear regression models to investigate the association between continuous anthropometric outcomes and maternal urinary mercury or neonate cord blood mercury. We also examined the association between LBW and PTB and the season that pregnancy began. Results showed higher rates of PTB and LBW in this cohort of women compared to other studies. Pregnancies beginning in winter (December, January, February) were at increased odds of LBW births compared with births from pregnancies that began in all other months (OR7.52 [95% CI 1.65, 34.29]). We observed no association between maternal exposure to Hg, and either LBW or PTB. The apparent lack of association is consistent with other studies. Further examination of seasonal association with LBW is warranted.

Maternal Mercury Exposure, Season of Conception and Adverse Birth Outcomes in an Urban Immigrant Community in Brooklyn, New York, U.S.A.

PubMed Central

Bashore, Cynthia J.; Geer, Laura A.; He, Xin; Puett, Robin; Parsons, Patrick J.; Palmer, Christopher D.; Steuerwald, Amy J.; Abulafia, Ovadia; Dalloul, Mudar; Sapkota, Amir

2014-01-01

Adverse birth outcomes including preterm birth (PTB: <37 weeks gestation) and low birth weight (LBW: <2500 g) can result in severe infant morbidity and mortality. In the United States, there are racial and ethnic differences in the prevalence of PTB and LBW. We investigated the association between PTB and LBW with prenatal mercury (Hg) exposure and season of conception in an urban immigrant community in Brooklyn, New York. We recruited 191 pregnant women aged 18–45 in a Brooklyn Prenatal Clinic and followed them until delivery. Urine specimens were collected from the participants during the 6th to 9th month of pregnancy. Cord blood specimens and neonate anthropometric data were collected at birth. We used multivariate logistic regression models to investigate the odds of LBW or PTB with either maternal urinary mercury or neonate cord blood mercury. We used linear regression models to investigate the association between continuous anthropometric outcomes and maternal urinary mercury or neonate cord blood mercury. We also examined the association between LBW and PTB and the season that pregnancy began. Results showed higher rates of PTB and LBW in this cohort of women compared to other studies. Pregnancies beginning in winter (December, January, February) were at increased odds of LBW births compared with births from pregnancies that began in all other months (OR7.52 [95% CI 1.65, 34.29]). We observed no association between maternal exposure to Hg, and either LBW or PTB. The apparent lack of association is consistent with other studies. Further examination of seasonal association with LBW is warranted. PMID:25153469

Amniotic Fluid Metabolomic Analysis in Spontaneous Preterm Birth

PubMed Central

Jones, Janice; Gunst, Phillip R.; Kacerovsky, Marian; Fortunato, Stephen J.; Saade, George R.; Basraon, Sanmaan

2014-01-01

Objective: To identify metabolic changes associated with early spontaneous preterm birth (PTB; <34 weeks) and term births, using high-throughput metabolomics of amniotic fluid (AF) in African American population. Method: In this study, AF samples retrieved from spontaneous PTB (<34 weeks [n = 25]) and normal term birth (n = 25) by transvaginal amniocentesis at the time of labor prior to delivery were subjected to metabolomics analysis. Equal volumes of samples were subjected to a standard solvent extraction method and analyzed using gas chromatography/mass spectrometry (MS) and liquid chromatography/MS/MS. Biochemicals were identified through matching of ion features to a library of biochemical standards. After log transformation and imputation of minimum observed values for each compound, t test, correlation tests, and false discovery rate corrections were used to identify differentially regulated metabolites. Data were controlled for clinical/demographic variables and medication during pregnancy. Results: Of 348 metabolites measured in AF samples, 121 metabolites had a gestational age effect and 116 differed significantly between PTB and term births. A majority of significantly altered metabolites could be classified into 3 categories, namely, (1) liver function, (2) fatty acid and coenzyme A (CoA) metabolism, and (3) histidine metabolism. The signature of altered liver function was apparent in many cytochrome P450-related pathways including bile acids, steroids, xanthines, heme, and phase II detoxification of xenobiotics with the largest fold change seen with pantothenol, a CoA synthesis inhibitor that was 8-fold more abundant in PTB. Conclusion: Global metabolic profiling of AF revealed alteration in hepatic metabolites involving xenobiotic detoxification and CoA metabolism in PTB. Maternal and/or fetal hepatic function differences may be developmentally related and its contribution PTB as a cause or effect of PTB is still unclear. PMID:24440995

The Relation of Neighborhood Income to the Age-Related Patterns of Preterm Birth Among White and African-American Women: The Effect of Cigarette Smoking.

PubMed

Hibbs, Shayna; Rankin, Kristin M; David, Richard J; Collins, James W

2016-07-01

Objectives We investigated the contributions of cigarette smoking to the age-related patterns of preterm (<37 weeks) birth (PTB) rates among African-American and White women within the context of lifelong neighborhood income. Methods Stratified and multilevel logistic regression analyses were performed on an Illinois transgenerational dataset of non-Hispanic White and African-American infants (1989-1991) and their mothers (1956-1976) with appended US census income information. Among non-smoking African-American women (n = 20,107) with a lifelong residence in lower income neighborhoods, PTB rates decreased from 18.5 % for teens to 15.0 % for 30-35 year-olds, p < 0.0001. The opposite pattern occurred among African-American women smokers (n = 5936) with a lifelong residence in lower income neighborhoods, p < 0.01. Among upwardly mobile African-American women smokers (n = 756), PTB rates increased from 11.1 % for teens to 24.9 % for 30-35 year-olds, p < 0.05. Cigarette smoking was not associated with an age-related increase in PTB rates among African-American women with a lifelong residence in upper income neighborhoods. No subgroup of White women, even cigarette smokers with a lifelong residence in lower income neighborhoods, exhibited weathering with regard to PTB. Conclusions A weathering pattern of rising PTB rates with advancing age occurs only among African-American women cigarette smokers with an early-life or lifelong residence in lower income neighborhoods, underscoring the public health policy importance of targeted smoking cessation programs in eliminating the racial disparity in the age-related patterns of PTB rates.

Impact of IL1B gene polymorphisms and interleukin 1B levels on susceptibility to spontaneous preterm birth.

PubMed

Langmia, Immaculate M; Apalasamy, Yamunah D; Omar, Siti Z; Mohamed, Zahurin

2016-11-01

Genetic factors influence susceptibility to preterm birth (PTB) and the immune pathway of PTB that involves the production of cytokines such as interleukins has been implicated in PTB disease. The aim of this study is to investigate the association of interleukin 1β (IL1B) gene polymorphisms and IL1B levels with spontaneous PTB. Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the Sequenom MassARRAY platform. Maternal plasma was used to measure IL1B levels. There was no significant association between the allelic and genotype distribution of IL1B single nucleotide polymorphism (SNP) (rs1143634, rs1143627, rs16944) and the risk of PTB among Malaysian Malay women (rs1143634, P=0.722; rs1143627, P=0.543; rs16944, P=0.615). However, IL1B levels were significantly different between women who delivered preterm compared with those who delivered at term (P=0.030); high mean levels were observed among Malay women who delivered at preterm (mean=32.52) compared with term (mean=21.68). IL1B SNPs were not associated with IL1B plasma levels. This study indicates a significant association between IL1B levels and reduced risk of PTB among the Malaysian Malay women. This study shows the impact of IL1B levels on susceptibility to PTB disease; however, the high levels of IL1B observed among women in the preterm group are not associated with IL1B SNPs investigated in this study; IL1B high levels may be because of other factors not explored in this study and therefore warrant further investigation.

Evaluation of Long Term Performance of Continuously Running Atomic Fountains

DTIC Science & Technology

2014-05-28

at least on the time frame of the accuracy evaluations. For example, the PTB has produced an excellent timescale based on a single caesium fountain...at PTB , which are beam standards. Figure 7. Relative frequency of NRF5 and each caesium fountain measurement reported to TAI. The (three) fountains...at LNE-SYRTE and (the two) at PTB are differentiated from the other labs reporting (NIST, NPL and one report from NICT). 6. Conclusion To summarize

Occupational, Environmental, and Lifestyle Factors and their Contribution to Preterm Birth – An Overview

PubMed Central

Kumar, Sunil; Sharma, Surendra; Thaker, Riddhi

2017-01-01

Preterm birth (PTB) is a significant public health concern and a leading cause of infant mortality and morbidity worldwide and often contributes to various health complications later in life. More than 60% of PTBs occur in Africa and south Asia. This overview discusses the available information on occupational, environmental, and lifestyle factors and their contribution to PTB and proposes new etiological explanations that underlie this devastating pregnancy complication. Several factors such as emotional, stress, social, racial, maternal anxiety, multiple pregnancies, infections during pregnancy, diabetes and high blood pressure, and in-vitro fertilization pregnancy have been shown to be associated with PTB. Data are emerging that occupational, environmental exposure and lifestyle factors might also be associated in part with PTB, however, they are at best limited and inconclusive. Nevertheless, data on heavy metals such as lead, air pollutants and particulate matters, bisphenol A, phthalate compounds, and environmental tobacco smoke (ETS) are promising and point to higher incidence of PTB associated with exposure to them. Thus, these observations can be used to advise pregnant women or women of reproductive age to avoid such exposures and adopt positive lifestyle to protect pregnancy and normal fetal development. There is a need to conduct well-planned epidemiological studies that include all the pathology causing factors that may contribute to adverse pregnancy outcomes, including PTB. PMID:29391742

Occupational, Environmental, and Lifestyle Factors and their Contribution to Preterm Birth - An Overview.

PubMed

Kumar, Sunil; Sharma, Surendra; Thaker, Riddhi

2017-01-01

Preterm birth (PTB) is a significant public health concern and a leading cause of infant mortality and morbidity worldwide and often contributes to various health complications later in life. More than 60% of PTBs occur in Africa and south Asia. This overview discusses the available information on occupational, environmental, and lifestyle factors and their contribution to PTB and proposes new etiological explanations that underlie this devastating pregnancy complication. Several factors such as emotional, stress, social, racial, maternal anxiety, multiple pregnancies, infections during pregnancy, diabetes and high blood pressure, and in-vitro fertilization pregnancy have been shown to be associated with PTB. Data are emerging that occupational, environmental exposure and lifestyle factors might also be associated in part with PTB, however, they are at best limited and inconclusive. Nevertheless, data on heavy metals such as lead, air pollutants and particulate matters, bisphenol A, phthalate compounds, and environmental tobacco smoke (ETS) are promising and point to higher incidence of PTB associated with exposure to them. Thus, these observations can be used to advise pregnant women or women of reproductive age to avoid such exposures and adopt positive lifestyle to protect pregnancy and normal fetal development. There is a need to conduct well-planned epidemiological studies that include all the pathology causing factors that may contribute to adverse pregnancy outcomes, including PTB.

Association between Exposure to Endocrine Disruptors in Drinking Water and Preterm Birth, Taking Neighborhood Deprivation into Account: A Historic Cohort Study.

PubMed

Albouy-Llaty, Marion; Limousi, Frédérike; Carles, Camille; Dupuis, Antoine; Rabouan, Sylvie; Migeot, Virginie

2016-08-09

The relationship between preterm birth (PTB) and endocrine disruptor exposure in drinking-water has only occasionally been studied. The objective of this work was to investigate the relation between exposure to atrazine metabolites, or atrazine/nitrate mixtures, in drinking-water during pregnancy and prevalence of PTB neonates, while taking neighborhood deprivation into account. A historic cohort study in Deux-Sèvres, France, between 2005 and 2010 with a multiple imputation model for data of exposure to atrazine metabolites and a logistic regression were carried out. We included 13,654 mother/neonate pairs living in 279 different census districts. The prevalence of PTB was 4%. Average atrazine metabolite concentration was 0.019 ± 0.009 (0.014-0.080) µg/L and 39% of mothers lived in less deprived areas. The individual data were associated with risk of PTB. The risk of PTB when exposed to highest concentration of atrazine metabolite adjusted for confounders, was ORa 1.625 95% CI [0.975; 2.710]. Taking, or not, neighborhood deprivation into account did not change the result. Exposure to atrazine/nitrate mixtures remained non-significant. Even if we took neighborhood deprivation into account, we could not show a significant relationship between exposure to atrazine metabolites, or mixtures, in drinking-water during the second trimester of pregnancy and PTB.

Modulation of dendritic cell and monocyte subsets in tuberculosis-diabetes co-morbidity upon standard tuberculosis treatment

PubMed Central

Kumar, Nathella Pavan; Moideen, Kadar; Sivakumar, Shanmugam; Menon, Pradeep A; Viswanathan, Vijay; Kornfeld, Hardy; Babu, Subash

2016-01-01

Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis (PTB), with development of DM pandemic in countries where tuberculosis (TB) is also endemic. However, the effect of anti-TB treatment on the changes in dentritic cell (DC) and monocyte subset phenotype in TB-DM co-morbidity is not well understood. In this study, we characterized the frequency of DC and monocyte subsets in individuals with PTB with (PTB-DM) or without coincident diabetes mellitus (PTB-NDM) before, during and after completion of anti-TB treatment. PTB-DM is characterized by diminished frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes at baseline and 2 months of anti-TB treatment but not following 6 months of treatment completion in comparison to PTB-NDM. DC and monocyte subsets exhibit significant but borderline correlation with fasting blood glucose and glycated hemoglobin levels. Finally, while minor changes in the DC and monocyte compartment were observed at 2 months of treatment, significantly increased frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes were observed at the successful completion of anti-TB treatment. Our data show that coincident diabetes alters the frequencies of innate subset distribution of DC and monocytes in TB-DM co-morbidity and suggests that most of these changes are reversible following anti-TB therapy. PMID:27865391

Assisted reproduction and risk of preterm birth in singletons by infertility diagnoses and treatment modalities: a population-based study.

PubMed

Dunietz, Galit Levi; Holzman, Claudia; Zhang, Yujia; Li, Chenxi; Todem, David; Boulet, Sheree L; McKane, Patricia; Kissin, Dmitry M; Copeland, Glenn; Bernson, Dana; Diamond, Michael P

2017-11-01

The purpose of this study is to examine the spectrum of infertility diagnoses and assisted reproductive technology (ART) treatments in relation to risk of preterm birth (PTB) in singletons. Population-based assisted reproductive technology surveillance data for 2000-2010 were linked with birth certificates from three states: Florida, Massachusetts, and Michigan, resulting in a sample of 4,370,361 non-ART and 28,430 ART-related singletons. Logistic regression models with robust variance estimators were used to compare PTB risk among singletons conceived with and without ART, the former grouped by parental infertility diagnoses and treatment modalities. Demographic and pregnancy factors were included in adjusted analyses. ART was associated with increased PTB risk across all infertility diagnosis groups and treatment types: for conventional ART, adjusted relative risks ranged from 1.4 (95% CI 1.0, 1.9) for male infertility to 2.4 (95% CI 1.8, 3.3) for tubal ligation. Adding intra-cytoplasmic sperm injection and/or assisted hatching to conventional ART treatment did not alter associated PTB risks. Singletons conceived by mothers without infertility diagnosis and with donor semen had an increased PTB risk relative to non-ART singletons. PTB risk among ART singletons is increased within each treatment type and all underlying infertility diagnosis, including male infertility. Preterm birth in ART singletons may be attributed to parental infertility, ART treatments, or their combination.

Association between Exposure to Endocrine Disruptors in Drinking Water and Preterm Birth, Taking Neighborhood Deprivation into Account: A Historic Cohort Study

PubMed Central

Albouy-Llaty, Marion; Limousi, Frédérike; Carles, Camille; Dupuis, Antoine; Rabouan, Sylvie; Migeot, Virginie

2016-01-01

Background: The relationship between preterm birth (PTB) and endocrine disruptor exposure in drinking-water has only occasionally been studied. The objective of this work was to investigate the relation between exposure to atrazine metabolites, or atrazine/nitrate mixtures, in drinking-water during pregnancy and prevalence of PTB neonates, while taking neighborhood deprivation into account. Method: A historic cohort study in Deux-Sèvres, France, between 2005 and 2010 with a multiple imputation model for data of exposure to atrazine metabolites and a logistic regression were carried out. Results: We included 13,654 mother/neonate pairs living in 279 different census districts. The prevalence of PTB was 4%. Average atrazine metabolite concentration was 0.019 ± 0.009 (0.014–0.080) µg/L and 39% of mothers lived in less deprived areas. The individual data were associated with risk of PTB. The risk of PTB when exposed to highest concentration of atrazine metabolite adjusted for confounders, was ORa 1.625 95% CI [0.975; 2.710]. Taking, or not, neighborhood deprivation into account did not change the result. Exposure to atrazine/nitrate mixtures remained non-significant. Conclusions: Even if we took neighborhood deprivation into account, we could not show a significant relationship between exposure to atrazine metabolites, or mixtures, in drinking-water during the second trimester of pregnancy and PTB. PMID:27517943

Influenza Pandemics and Tuberculosis Mortality in 1889 and 1918: Analysis of Historical Data from Switzerland

PubMed Central

Zürcher, Kathrin; Zwahlen, Marcel; Ballif, Marie; Rieder, Hans L.; Egger, Matthias

2016-01-01

Background Tuberculosis (TB) mortality declined in the northern hemisphere over the last 200 years, but peaked during the Russian (1889) and the Spanish (1918) influenza pandemics. We studied the impact of these two pandemics on TB mortality. Methods We retrieved historic data from mortality registers for the city of Bern and countrywide for Switzerland. We used Poisson regression models to quantify the excess pulmonary TB (PTB) mortality attributable to influenza. Results Yearly PTB mortality rates increased during both influenza pandemics. Monthly influenza and PTB mortality rates peaked during winter and early spring. In Bern, for an increase of 100 influenza deaths (per 100,000 population) monthly PTB mortality rates increased by a factor of 1.5 (95%Cl 1.4–1.6, p<0.001) during the Russian, and 3.6 (95%Cl 0.7–18.0, p = 0.13) during the Spanish pandemic. Nationally, the factor was 2.0 (95%Cl 1.8–2.2, p<0.001) and 1.5 (95%Cl 1.1–1.9, p = 0.004), respectively. We did not observe any excess cancer or extrapulmonary TB mortality (as a negative control) during the influenza pandemics. Conclusions We demonstrate excess PTB mortality during historic influenza pandemics in Switzerland, which supports a role for influenza vaccination in PTB patients in high TB incidence countries. PMID:27706149

Protosappanin B protects PC12 cells against oxygen-glucose deprivation-induced neuronal death by maintaining mitochondrial homeostasis via induction of ubiquitin-dependent p53 protein degradation.

PubMed

Zeng, Ke-Wu; Liao, Li-Xi; Zhao, Ming-Bo; Song, Fang-Jiao; Yu, Qian; Jiang, Yong; Tu, Peng-Fei

2015-03-15

Protosappanin B (PTB) is a bioactive dibenzoxocin derivative isolated from Caesalpinia sappan L. Here, we investigated the neuroprotective effects and the potential mechanisms of PTB on oxygen-glucose deprivation (OGD)-injured PC12 cells. Results showed that PTB significantly increased cell viability, inhibited cell apoptosis and up-regulated the expression of growth-associated protein 43 (a marker of neural outgrowth). Moreover, our study revealed that PTB effectively maintained mitochondrial homeostasis by up-regulation of mitochondrial membrane potential (MMP), inhibition of cytochrome c release from mitochondria and inactivation of mitochondrial caspase-9/3 apoptosis pathway. Further study showed that PTB significantly promoted cytoplasmic component degradation of p53 protein, a key negative regulator for mitochondrial function, resulting in a release of Bcl-2 from p53-Bcl-2 complex and an enhancing translocation of Bcl-2 to mitochondrial outer membrane. Finally, we found the degradation of p53 protein was induced by PTB via activation of a MDM2-dependent ubiquitination process. Taken together, our findings provided a new viewpoint of neuronal protection strategy for anoxia and ischemic injury with natural small molecular dibenzoxocin derivative by activating ubiquitin-dependent p53 protein degradation as well as increasing mitochondrial function. Copyright © 2015 Elsevier B.V. All rights reserved.

The value of initial cavitation to predict re-treatment with pulmonary tuberculosis.

PubMed

Huang, Qiusheng; Yin, Yongmei; Kuai, Shougang; Yan, Yan; Liu, Jun; Zhang, YingYing; Shan, Zhongbao; Gu, Lan; Pei, Hao; Wang, Jun

2016-05-06

Pulmonary cavitation is the classic hallmark of pulmonary tuberculosis (PTB) and is the site of very high mycobacterial burden associated with antimycobacterial drug resistance and treatment failure. The objective of this study was to investigate the relationship between re-treatment PTB and initial pulmonary cavitation coordinated with other clinical factors. We conducted a case-control study of 291 newly diagnosed cases of pulmonary TB in The Infectious Hospital of Wuxi from Dec 2009 to Dec 2011 with complete follow-up information until December 31st of 2014. 68 patients were followed-up with PTB re-treatment; the rest of the PTB patients (n = 223) had completed anti-TB treatment, and cured without re-treatment were selected as controls. The univariate analysis [hazard ratio (HR) 1.885, 95 % CI 1.170-3.035, P = 0.009] and the multivariable analysis (HR 2.242, 95 % CI 1.294-3.882, P = 0.004) demonstrated that the initial pulmonary cavitation was a prognostic predictor for TB re-treatment. Additionally, the re-treatment rates in PTB patients with cavitation and no-cavitation were 27.1 and 15.5 %, respectively, with significant difference (log-rank test; P = 0.010). Other factors, age of ≥60 and history of smoking, were also prognostic variables. Initial pulmonary cavitation of chest X-ray was a significant predictor for PTB re-treatment.

1993 Intercomparison of Photometric Units Maintained at NIST (USA) and PTB (Germany)

PubMed Central

Ohno, Yoshihiro; Sauter, Georg

1995-01-01

A bilateral intercomparison of photometric units between NIST, USA and PTB, Germany has been conducted to update the knowledge of the relationship between the photometric units disseminated in each country. The luminous intensity unit (cd) and the luminous flux unit (lm) maintained at both laboratories are compared by circulating transfer standard lamps. Also, the photometric responsivity sv is compared by circulating a V(λ)-corrected detector with a built-in current-to-voltage converter. The results show that the difference of luminous intensity unit between NIST and PTB, (PTB-NIST)/NIST, is 0.2 % with a relative expanded uncertainty (coverage factor k = 2) of 0.24 %. The difference is reduced significantly from that at the 1985 CCPR intercomparison (0.9 %). The difference in luminous flux unit, (PTB – NIST)/NIST, is found to be 1.5 % with a relative expanded uncertainty (coverage factor k =2) of 0.15 %. The difference remained nearly the same as that at the 1985 intercomparison (1.6 %). These results agree with what is predicted from the history of maintaining the units at each laboratory. PMID:29151737

Tracing neuronal circuits in transgenic animals by transneuronal control of transcription (TRACT)

PubMed Central

Huang, Ting-hao; Niesman, Peter; Arasu, Deepshika; Lee, Donghyung; De La Cruz, Aubrie L; Callejas, Antuca; Hong, Elizabeth J

2017-01-01

Understanding the computations that take place in brain circuits requires identifying how neurons in those circuits are connected to one another. We describe a technique called TRACT (TRAnsneuronal Control of Transcription) based on ligand-induced intramembrane proteolysis to reveal monosynaptic connections arising from genetically labeled neurons of interest. In this strategy, neurons expressing an artificial ligand (‘donor’ neurons) bind to and activate a genetically-engineered artificial receptor on their synaptic partners (‘receiver’ neurons). Upon ligand-receptor binding at synapses the receptor is cleaved in its transmembrane domain and releases a protein fragment that activates transcription in the synaptic partners. Using TRACT in Drosophila we have confirmed the connectivity between olfactory receptor neurons and their postsynaptic targets, and have discovered potential new connections between neurons in the circadian circuit. Our results demonstrate that the TRACT method can be used to investigate the connectivity of neuronal circuits in the brain. PMID:29231171

Reducing recurrent preterm births: best evidence for transitioning to predictive and preventative strategies.

PubMed

Cypher, Rebecca L

2012-01-01

Women who have delivered an infant between 16 and 36 weeks' gestation have an increased risk of preterm birth (PTB) in a subsequent pregnancy. The high incidence of recurrent PTB remains relatively unchanged despite intensive research efforts and advances in perinatal care. Attempts to decrease the incidence of recurrent PTB have not always been successful, with research efforts being focused on clinical, pharmacotherapy and biochemical, and ultrasound strategies. Fortunately, there is adequate evidence in the literature to justify clinical management guidelines that may impact the PTB rate: smoking cessation, treatment of asymptomatic bacteriuria, transvaginal ultrasonography of the cervix, administration of vaginal progesterone or 17α-hydroxyprogesterone caproate, cerclage, and fetal fibronectin. This article is intended to give brief highlights of these strategies and the current science that supports their conclusions.

Preterm Birth and Its Long-Term Effects: Methylation to Mechanisms

PubMed Central

Parets, Sasha E.; Bedient, Carrie E.; Menon, Ramkumar; Smith, Alicia K.

2014-01-01

The epigenetic patterns established during development may influence gene expression over a lifetime and increase susceptibility to chronic disease. Being born preterm (<37 weeks of gestation) is associated with increased risk mortality and morbidity from birth until adulthood. This brief review explores the potential role of DNA methylation in preterm birth (PTB) and its possible long-term consequences and provides an overview of the physiological processes central to PTB and recent DNA methylation studies of PTB. PMID:25256426

Long-Term Instability of GPS-Based Time Transfer and Proposals for Improvements

DTIC Science & Technology

2011-01-01

receiver, or use of a completely independent technique such as Two-Way Satellite Time and Frequency Transfer ( TWSTFT ), helps to identify which receiver...is generated using not only the PTB’s Two-Way Satellite Time and Frequency Transfer ( TWSTFT or TW) links, but also links based on other PTB GNSS...including the PTB by X WX [1,2]; delay variations in other PTB time transfer systems would have an additive effect whether they were TWSTFT or GNSS

Unexpected: an interpretive description of parental traumas' associated with preterm birth.

PubMed

Lasiuk, Gerri C; Comeau, Thea; Newburn-Cook, Christine

2013-01-01

Preterm birth (PTB) places a considerable emotional, psychological, and financial burden on parents, families, health care resources, and society as a whole. Efforts to estimate these costs have typically considered the direct medical costs of the initial hospital and outpatient follow-up care but have not considered non-financial costs associated with PTB such as adverse psychosocial and emotional effects, family disruption, strain on relationships, alterations in self-esteem, and deterioration in physical and mental health. The aim of this inquiry is to understand parents' experience of PTB to inform the design of subsequent studies of the direct and indirect cost of PTB. The study highlights the traumatic nature of having a child born preterm and discusses implications for clinical care and further research. Through interviews and focus groups, this interpretive descriptive study explored parents' experiences of PTB. The interviews were audiotaped, transcribed, and analyzed for themes. Analysis was ongoing throughout the study and in subsequent interviews, parents were asked to reflect and elaborate on the emerging themes as they were identified. PTB is a traumatic event that shattered parents' taken-for-granted expectations of parenthood. For parents in our study, the trauma they experienced was not related to infant characteristics (e.g., gestational age, birth weight, Apgar scores, or length of stay in the NICU), but rather to prolonged uncertainty, lack of agency, disruptions in meaning systems, and alterations in parental role expectations. Our findings help to explain why things like breast feeding, kangaroo care, and family centered practices are so meaningful to parents in the NICU. As well as helping to (re)construct their role as parents, these activities afford parents a sense of agency, thereby moderating their own helplessness. These findings underscore the traumatic nature and resultant psychological distress related to PTB. Obstetrical and neonatal healthcare providers need to be educated about the symptoms of Acute Stress Disorder (ASD) and Posttraumatic Stress Disorder (PTSD) to better understand and support parents' efforts to adapt and to make appropriate referrals if problems develop. Longitudinal economic studies must consider the psychosocial implications of PTB to in order to determine the total related costs.

Trends of Tuberculosis Case Notification and Treatment Outcomes in the Sidama Zone, Southern Ethiopia: Ten-Year Retrospective Trend Analysis in Urban-Rural Settings

PubMed Central

Dangisso, Mesay Hailu; Datiko, Daniel Gemechu; Lindtjørn, Bernt

2014-01-01

Background Ethiopia is one of the high tuberculosis (TB) burden countries. An analysis of trends and differentials in case notifications and treatment outcomes of TB may help improve our understanding of the performance of TB control services. Methods A retrospective trend analysis of TB cases was conducted in the Sidama Zone in southern Ethiopia. We registered all TB cases diagnosed and treated during 2003–2012 from all health facilities in the Sidama Zone, and analysed trends of TB case notification rates and treatment outcomes. Results The smear positive (PTB+) case notification rate (CNR) increased from 55 (95% CI 52.5–58.4) to 111 (95% CI 107.4–114.4) per 105 people. The CNRs of PTB+ in people older than 45 years increased by fourfold, while the mortality of cases during treatment declined from 11% to 3% for smear negative (PTB-) (X2 trend, P<0.001) and from 5% to 2% for PTB+ (X2 trend, P<0.001). The treatment success was higher in rural areas (AOR 1.11; CI 95%: 1.03–1.2), less for PTB- (AOR 0.86; CI 95%: 0.80–0.92) and higher for extra-pulmonary TB (AOR 1.10; CI 95%: 1.02–1.19) compared to PTB+. A higher lost-to-follow up was observed in men (AOR 1.15; CI 95%: 1.06–1.24) and among PTB- cases (AOR 1.14; CI 95%: 1.03–1.25). More deaths occurred in PTB-cases (AOR 1.65; 95% CI: 1.44–1.90) and among cases older than 65 years (AOR 3.86; CI 95%: 2.94–5.10). Lastly, retreatment cases had a higher mortality than new cases (6% vs 3%). Conclusion Over the past decade TB CNRs and treatment outcomes improved, whereas the disparities of disease burden by gender and place of residence reduced and mortality declined. Strategies should be devised to address higher risk groups for poor treatment outcomes. PMID:25460363

Unexpected: an interpretive description of parental traumas’ associated with preterm birth

PubMed Central

2013-01-01

Background Preterm birth (PTB) places a considerable emotional, psychological, and financial burden on parents, families, health care resources, and society as a whole. Efforts to estimate these costs have typically considered the direct medical costs of the initial hospital and outpatient follow-up care but have not considered non-financial costs associated with PTB such as adverse psychosocial and emotional effects, family disruption, strain on relationships, alterations in self-esteem, and deterioration in physical and mental health. The aim of this inquiry is to understand parents’ experience of PTB to inform the design of subsequent studies of the direct and indirect cost of PTB. The study highlights the traumatic nature of having a child born preterm and discusses implications for clinical care and further research. Method Through interviews and focus groups, this interpretive descriptive study explored parents’ experiences of PTB. The interviews were audiotaped, transcribed, and analyzed for themes. Analysis was ongoing throughout the study and in subsequent interviews, parents were asked to reflect and elaborate on the emerging themes as they were identified. Results PTB is a traumatic event that shattered parents’ taken-for-granted expectations of parenthood. For parents in our study, the trauma they experienced was not related to infant characteristics (e.g., gestational age, birth weight, Apgar scores, or length of stay in the NICU), but rather to prolonged uncertainty, lack of agency, disruptions in meaning systems, and alterations in parental role expectations. Our findings help to explain why things like breast feeding, kangaroo care, and family centered practices are so meaningful to parents in the NICU. As well as helping to (re)construct their role as parents, these activities afford parents a sense of agency, thereby moderating their own helplessness. Conclusion These findings underscore the traumatic nature and resultant psychological distress related to PTB. Obstetrical and neonatal healthcare providers need to be educated about the symptoms of Acute Stress Disorder (ASD) and Posttraumatic Stress Disorder (PTSD) to better understand and support parents’ efforts to adapt and to make appropriate referrals if problems develop. Longitudinal economic studies must consider the psychosocial implications of PTB to in order to determine the total related costs. PMID:23445715

History of preterm birth and subsequent cardiovascular disease: a systematic review.

PubMed

Robbins, Cheryl L; Hutchings, Yalonda; Dietz, Patricia M; Kuklina, Elena V; Callaghan, William M

2014-04-01

A history of preterm birth (PTB) may be an important lifetime risk factor for cardiovascular disease (CVD) in women. We identified all peer-reviewed journal articles that met study criteria (English language, human studies, female, and adults ≥19 years old), that were found in the PubMed/MEDLINE databases, and that were published between Jan. 1, 1995, and Sept. 17, 2012. We summarized 10 studies that assessed the association between having a history of PTB and subsequent CVD morbidity or death. Compared with women who had term deliveries, women with any history of PTB had increased risk of CVD morbidity (variously defined; adjusted hazard ratio [aHR] ranged from 1.2-2.9; 2 studies), ischemic heart disease (aHR, 1.3-2.1; 3 studies), stroke (aHR, 1.7; 1 study), and atherosclerosis (aHR, 4.1; 1 study). Four of 5 studies that examined death showed that women with a history of PTB have twice the risk of CVD death compared with women who had term births. Two studies reported statistically significant higher risk of CVD-related morbidity and death outcomes (variously defined) among women with ≥2 pregnancies that ended in PTBs compared with women who had at least 2 births but which ended in only 1 PTB. Future research is needed to understand the potential impact of enhanced monitoring of CVD risk factors in women with a history of PTB on risk of future CVD risk. Copyright © 2014 Mosby, Inc. All rights reserved.

History of preterm birth and subsequent cardiovascular disease: a systematic review

PubMed Central

Robbins, Cheryl L.; Hutchings, Yalonda; Dietz, Patricia M.; Kuklina, Elena V.; Callaghan, William M.

2015-01-01

A history of preterm birth (PTB) may be an important lifetime risk factor for cardiovascular disease (CVD) in women. We identified all peer-reviewed journal articles that met study criteria (English language, human studies, female, and adults ≥19 years old), that were found in the PubMed/MEDLINE databases, and that were published between Jan. 1, 1995, and Sept. 17, 2012. We summarized 10 studies that assessed the association between having a history of PTB and subsequent CVD morbidity or death. Compared with women who had term deliveries, women with any history of PTB had increased risk of CVD morbidity (variously defined; adjusted hazard ratio [aHR] ranged from 1.2e2.9; 2 studies), ischemic heart disease (aHR, 1.3e2.1; 3 studies), stroke (aHR, 1.7; 1 study), and atherosclerosis (aHR, 4.1; 1 study). Four of 5 studies that examined death showed that women with a history of PTB have twice the risk of CVD death compared with women who had term births. Two studies reported statistically significant higher risk of CVD—rerelated morbidity and death outcomes (variously defined) among women with —2 pregnancies that ended in PTBs compared with women who had at least 2 births but which ended in only 1 PTB. Future research is needed to understand the potential impact of enhanced monitoring of CVD risk factors in women with a history of PTB on risk of future CVD risk. PMID:24055578

Propeller-shaped acceptors for high-performance non-fullerene solar cells: Importance of the rigidity of molecular geometry

DOE PAGES

Wu, Qinghe; Zhao, Donglin; Yang, Jinghui; ...

2017-01-06

This study describes the synthesis and application of βTPB6 and βTPB6-C as electron acceptors for organic solar cells. Compound βTPB6 contains four covalently bonded PDIs with a BDT-Th core at the β-position. The free rotation of PDIs renders βTPB6 with varying molecular geometries. The cyclization of βTPB6 yields βTPB6-C with high rigidity of the molecular geometry and enlarged conjugated skeleton. The inverted solar cells based on βTPB6-C and PTB7-Th as the donor polymer exhibited the highest efficiency of 7.69% with V oc of 0.92 V, J sc of 14.9 mAcm –2, and FF of 0.56, which is 31% higher thanmore » that for βTPB6 based devices. The larger fraction of βTPB6-C and PTB7-Th than that of βTPB6:PTB7-Th in a blend film takes a face-on orientation packing pattern for π-systems that benefits the charge transport and hence higher PCE value than that for βTPB6:PTB7-Th. It was also found that a proper DIO:DPE additive further enhances this trend, which results in an increase of the PCE value for βTPB6-C:PTB7-Th while decreasing the PCE value for βTPB6:PTB7-Th.« less

Variation in birth outcomes by mother's country of birth among non-Hispanic black women in the United States.

PubMed

Elo, Irma T; Vang, Zoua; Culhane, Jennifer F

2014-12-01

Rates of prematurity (PTB) and small-for-gestational age (SGA) were compared between US-born and foreign-born non-Hispanic black women. Comparisons were also made between Sub-Saharan African-born and Caribbean-born black women and by maternal country of birth within the two regions. Comparisons were adjusted for sociodemographic, health behavioral and medical risk factors available on the birth record. Birth record data (2008) from all states (n = 27) where mother's country of birth was recorded were used. These data comprised 58 % of all singleton births to non-Hispanic black women in that year. Pearson Chi square and logistic regression were used to investigate variation in the rates of PTB and SGA by maternal nativity. Foreign-born non-Hispanic black women had significantly lower rates of PTB (OR 0.727; CI 0. 726, 0.727) and SGA (OR 0.742; CI 0.739-0.745) compared to US-born non-Hispanic black women in a fully adjusted model. Sub-Saharan African-born black women compared to Caribbean-born black women had significantly lower rates of PTB and SGA. Within each region, the rates of PTB and SGA varied by mother's country of birth. These differences could not be explained by adjustment for known risk factors obtained from vital records. Considerable heterogeneity in rates of PTB and SGA among non-Hispanic black women in the US by maternal nativity was documented and remained unexplained after adjustment for known risk factors.

Association between prenatal care utilization and risk of preterm birth among Chinese women.

PubMed

Zhang, Bin; Yang, Rong; Liang, Sheng-Wen; Wang, Jing; Chang, Jen Jen; Hu, Ke; Dong, Guang-Hui; Hu, Rong-Hua; Flick, Louise H; Zhang, Yi-Ming; Zhang, Dan; Li, Qing-Jie; Zheng, Tong-Zhang; Xu, Shun-Qing; Yang, Shao-Ping; Qian, Zheng-Min

2017-08-01

It is recognized that prenatal care plays an important role in reducing adverse birth. Chinese pregnant women with medical condition were required to seek additional health care based on the recommended at least 5 times health care visits. This study was to estimate the association between prenatal care utilization (PCU) and preterm birth (PTB), and to investigate if medical conditions during pregnancy modified the association. This population-based case control study sampled women with PTB as cases; one control for each case was randomly selected from women with term births. The Electronic Perinatal Health Care Information System (EPHCIS) and a questionnaire were used for data collection. The PCU was measured by a renewed Prenatal Care Utilization (APNCU) index. Logistic regression models were used to estimate odds ratios (OR) and the 95% confidence interval (95% CI). Totally, 2393 women with PTBs and 4263 women with term births were collected. In this study, 695 (10.5%) women experienced inadequate prenatal care, and 5131 (77.1%) received adequate plus prenatal care. Inadequate PCU was associated with PTB (adjusted OR: 1.41, 95% CI: 1.32-1.84); the similar positive association was found between adequate plus PCU and PTB. Among women with medical conditions, these associations still existed; but among women without medical conditions, the association between inadequate PCU and PTB disappeared. Our data suggests that women receiving inappropriate PCU are at an increased risk of having PTB, but it does depend on whether the woman has a medical condition during pregnancy.

Maternal history of adoption or foster care placement in childhood: a risk factor for preterm birth.

PubMed

Bublitz, Margaret H; Rodriguez, Daniel; Polly Gobin, Asi; Waldemore, Marissa; Magee, Susanna; Stroud, Laura R

2014-10-01

The objective of the study was to assess the impact of maternal history of adoption or foster care placement in childhood on the risk for preterm birth (PTB), controlling for other known risk factors for PTB. Participants were 302 pregnant women from a low-income, diverse sample drawn from 2 intensive prospective studies of maternal mood and behavior and fetal and infant development. Gestational age was determined by best obstetric estimate. Maternal history of adoption or foster care placement prior to age 18 years was determined by maternal report. Other maternal characteristics, including maternal medical conditions, psychosocial characteristics, and health behaviors, were measured during the second and third trimesters of pregnancy. The odds of delivering preterm (gestational age <37 weeks) were approximately 4 times greater among women with a history of childhood adoption or foster care placement compared with women who were never placed out of the home during childhood. This association remained significant after adjusting for other known risk factors for PTB including maternal medical conditions, psychosocial characteristics, and negative health behaviors in pregnancy. Findings suggest that a history of adoption/foster care placement is an important risk factor for PTB and may be comparable with other established risk factors for PTB including prior history of PTB, body mass index, African-American race, and advanced maternal age. More studies are needed to understand why women with placement histories may be at increased risk to deliver preterm. Copyright © 2014 Elsevier Inc. All rights reserved.

Risk of Spontaneous Preterm Birth in Relation to Maternal Depressive, Anxiety and Stress Symptoms

PubMed Central

Sanchez, Sixto E.; Puente, Gabriella C.; Atencio, Guillermo; Qiu, Chungfang; Yanez, David; Gelaye, Bizu; Williams, Michelle A.

2013-01-01

Objective To examine the risk of preterm birth (PTB) in relation to maternal psychiatric symptoms during pregnancy in Peruvian women. Methods This case control study included 479 PTB cases and 480 term controls. In-person interviews were conducted to assess women’s depressive, anxiety and stress symptoms using the Patient Health Questionnaire (PHQ-9) and the Depression Anxiety Stress Scales (DASS-21). Multivariable logistic regression procedures were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results Compared with women reporting no or minimal depressive symptoms, the aOR (95% CI) for PTB associated with consecutive severity of depressive symptoms based on the PHQ-9 assessment method were as follows: mild 2.22 (95% CI 1.64–3.00) and moderate-severe 3.67 (95% CI 2.09–6.46). The corresponding aORs for mild, moderate, and moderate- severe depressive symptoms based on the DASS-21 assessment were, 1.00 (reference), 3.82 (95% CI 1.90–7.66) and 2.90 (95% CI 1.66–5.04), respectively. A positive gradient was observed for the odds of PTB with severity of anxiety (ptrend <0.001) and stress symptoms (ptrend <0.001). Conclusions The odds of PTB are increased in pregnant Peruvian women with psychiatric symptoms. Efforts to screen and treat affected women may modify risks of PTB and possibly other associated disorders. PMID:23447915

Propeller-shaped acceptors for high-performance non-fullerene solar cells: Importance of the rigidity of molecular geometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Qinghe; Zhao, Donglin; Yang, Jinghui

This study describes the synthesis and application of βTPB6 and βTPB6-C as electron acceptors for organic solar cells. Compound βTPB6 contains four covalently bonded PDIs with a BDT-Th core at the β-position. The free rotation of PDIs renders βTPB6 with varying molecular geometries. The cyclization of βTPB6 yields βTPB6-C with high rigidity of the molecular geometry and enlarged conjugated skeleton. The inverted solar cells based on βTPB6-C and PTB7-Th as the donor polymer exhibited the highest efficiency of 7.69% with V oc of 0.92 V, J sc of 14.9 mAcm –2, and FF of 0.56, which is 31% higher thanmore » that for βTPB6 based devices. The larger fraction of βTPB6-C and PTB7-Th than that of βTPB6:PTB7-Th in a blend film takes a face-on orientation packing pattern for π-systems that benefits the charge transport and hence higher PCE value than that for βTPB6:PTB7-Th. It was also found that a proper DIO:DPE additive further enhances this trend, which results in an increase of the PCE value for βTPB6-C:PTB7-Th while decreasing the PCE value for βTPB6:PTB7-Th.« less

Does adjunctive use of progesterone in women with cerclage improve prevention of preterm birth?

PubMed

Sinkey, Rachel G; Garcia, Mercedes R; Odibo, Anthony O

2018-01-01

To evaluate outcomes among pregnancies with cerclage as compared to cerclage and adjunctive progesterone. A retrospective cohort study was performed from 1 October 2011-30 June 2015 including women with a singleton gestation with vaginal cerclage. Exclusion criteria included multiple gestations, simultaneous 17-alpha hydroxyprogesterone caproate (17-OHPC) and vaginal progesterone (vag-p) use, and patients lost to follow-up. Primary outcome was prevention of preterm birth less than 35 (PTB <35) weeks gestational age (GA). One hundred thirty-six patients met inclusion criteria; 73 women had cerclage only, 53 had cerclage and 17-OHPC, 10 had cerclage and vag-p. GA at cerclage placement was similar across groups (p = 0.068). There was a difference in prevention of PTB <35 weeks GA among groups (p = 0.035) with a trend toward earlier delivery among patients with cerclage and vag-p. Rates of PTB <35 weeks in the cerclage (29%) and cerclage and 17-OHPC groups (34%) were similar (p = 0.533). The odds ratio for risk of PTB <35 weeks among women with cerclage and vag-p as compared to all other patients was 5.21 (95%CI: 1.3-21.2). The combination of cerclage with intramuscular progesterone resulted in similar PTB prevention as compared to cerclage alone. There may be an association between cerclage, vaginal progesterone and higher rates of PTB which may be attributed to characteristics of the group rather than the therapies studied.

Maternal height and the risk of preterm birth and low birth weight: a systematic review and meta-analyses.

PubMed

Han, Zhen; Lutsiv, Olha; Mulla, Sohail; McDonald, Sarah D

2012-08-01

Preterm birth (PTB) and low birth weight (LBW) are the leading causes of neonatal morbidity and mortality, but the effect of maternal height on these outcomes continues to be debated. Our objective was to determine the relationships between maternal height and PTB and LBW. Medline and EMBASE were searched from their inceptions. Studies with a reference group that assessed the effect of maternal height on PTB (< 37 weeks) and LBW (< 2500 grams) in singletons were included. Data were extracted independently by two reviewers. Fifty-six studies were included involving 333 505 women. In the cohort studies, the unadjusted risk of PTB in short-statured women was increased (relative risk [RR] 1.23; 95% CI 1.11 to 1.37), as was the unadjusted risk of LBW (RR 1.81; 95% CI 1.47 to 2.23), although not all of the studies with adjusted data found the same association. Maternal tall stature was not associated with PTB (unadjusted RR 0.97; 95% CI 0.82 to 1.14), although LBW was decreased (unadjusted RR 0.56; 95% CI 0.46 to 0.69), but not in the adjusted data. From our complete systematic review and meta-analyses, to our knowledge the first in this area, we conclude that short-statured women have higher unadjusted risks of PTB and LBW and tall women have approximately one half the unadjusted risk of LBW of women of reference height.

Particulate Matter Exposure and Preterm Birth: Estimates of U.S. Attributable Burden and Economic Costs

PubMed Central

Trasande, Leonardo; Malecha, Patrick; Attina, Teresa M.

2016-01-01

Background: Preterm birth (PTB) rates (11.4% in 2013) in the United States remain high and are a substantial cause of morbidity. Studies of prenatal exposure have associated particulate matter ≤ 2.5 μm in diameter (PM2.5) and other ambient air pollutants with adverse birth outcomes; yet, to our knowledge, burden and costs of PM2.5-attributable PTB have not been estimated in the United States. Objectives: We aimed to estimate burden of PTB in the United States and economic costs attributable to PM2.5 exposure in 2010. Methods: Annual deciles of PM2.5 were obtained from the U.S. Environmental Protection Agency. We converted PTB odds ratio (OR), identified in a previous meta-analysis (1.15 per 10 μg/m3 for our base case, 1.07–1.16 for low- and high-end scenarios) to relative risk (RRs), to obtain an estimate that better represents the true relative risk. A reference level (RL) of 8.8 μg/m3 was applied. We then used the RR estimates and county-level PTB prevalence to quantify PM2.5-attributable PTB. Direct medical costs were obtained from the 2007 Institute of Medicine report, and lost economic productivity (LEP) was estimated using a meta-analysis of PTB-associated IQ loss, and well-established relationships of IQ loss with LEP. All costs were calculated using 2010 dollars. Results: An estimated 3.32% of PTBs nationally (corresponding to 15,808 PTBs) in 2010 could be attributed to PM2.5 (PM2.5 > 8.8 μg/m3). Attributable PTBs cost were estimated at $5.09 billion [sensitivity analysis (SA): $2.43–9.66 B], of which $760 million were spent for medical care (SA: $362 M–1.44 B). The estimated PM2.5 attributable fraction (AF) of PTB was highest in urban counties, with highest AFs in the Ohio Valley and the southern United States. Conclusions: PM2.5 may contribute substantially to burden and costs of PTB in the United States, and considerable health and economic benefits could be achieved through environmental regulatory interventions that reduce PM2.5 exposure in pregnancy. Citation: Trasande L, Malecha P, Attina TM. 2016. Particulate matter exposure and preterm birth: estimates of U.S. attributable burden and economic costs. Environ Health Perspect 124:1913–1918; http://dx.doi.org/10.1289/ehp.1510810 PMID:27022947

Antibiotics for treating bacterial vaginosis in pregnancy.

PubMed

McDonald, H M; Brocklehurst, P; Gordon, A

2007-01-24

Bacterial vaginosis is an imbalance of the normal vaginal flora with an overgrowth of anaerobic bacteria and a lack of the normal lactobacillary flora. Bacterial vaginosis during pregnancy has been associated with poor perinatal outcome and, in particular, preterm birth (PTB). Identification and treatment may reduce the risk of PTB and its consequences. To assess the effects of antibiotic treatment of bacterial vaginosis in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2006). Randomized trials comparing antibiotic treatment with placebo or no treatment, or comparing two or more antibiotic regimens in pregnant women with bacterial vaginosis or intermediate vaginal flora. Two review authors assessed trials and extracted data independently. We contacted study authors for additional information. We included fifteen trials of good quality, involving 5888 women. Antibiotic therapy was effective at eradicating bacterial vaginosis during pregnancy (Peto odds ratio (OR) 0.17, 95% confidence interval (CI) 0.15 to 0.20; 10 trials, 4357 women). Treatment did not reduce the risk of PTB before 37 weeks (Peto OR 0.91, 95% CI 0.78 to 1.06; 15 trials, 5888 women), or the risk of preterm prelabour rupture of membranes (PPROM) (Peto OR 0.88, 95% CI 0.61 to 1.28; four trials, 2579 women). However, treatment before 20 weeks' gestation may reduce the risk of preterm birth less than 37 weeks (Peto OR 0.63, 95% CI 0.48 to 0.84; five trials, 2387 women). In women with a previous PTB, treatment did not affect the risk of subsequent PTB (Peto OR 0.83, 95% CI 0.59 to 1.17, five trials of 622); however, it may decrease the risk of PPROM (Peto OR 0.14, 95% CI 0.05 to 0.38) and low birthweight (Peto OR 0.31, 95% CI 0.13 to 0.75)(two trials, 114 women). In women with abnormal vaginal flora (intermediate flora or bacterial vaginosis) treatment may reduce the risk of PTB before 37 weeks (Peto OR 0.51, 95% CI 0.32 to 0.81; two trials, 894 women). Clindamycin did not reduce the risk of PTB before 37 weeks (Peto OR 0.80, 95% CI 0.60 to 1.05; six trials, 2406 women). Antibiotic treatment can eradicate bacterial vaginosis in pregnancy. This review provides little evidence that screening and treating all pregnant women with asymptomatic bacterial vaginosis will prevent PTB and its consequences. However, there is some suggestion that treatment before 20 weeks' gestation may reduce the risk of PTB. This needs to be further verified by future trials.

Particulate Matter Exposure and Preterm Birth: Estimates of U.S. Attributable Burden and Economic Costs.

PubMed

Trasande, Leonardo; Malecha, Patrick; Attina, Teresa M

2016-12-01

Preterm birth (PTB) rates (11.4% in 2013) in the United States remain high and are a substantial cause of morbidity. Studies of prenatal exposure have associated particulate matter ≤ 2.5 μm in diameter (PM2.5) and other ambient air pollutants with adverse birth outcomes; yet, to our knowledge, burden and costs of PM2.5-attributable PTB have not been estimated in the United States. We aimed to estimate burden of PTB in the United States and economic costs attributable to PM2.5 exposure in 2010. Annual deciles of PM2.5 were obtained from the U.S. Environmental Protection Agency. We converted PTB odds ratio (OR), identified in a previous meta-analysis (1.15 per 10 μg/m3 for our base case, 1.07-1.16 for low- and high-end scenarios) to relative risk (RRs), to obtain an estimate that better represents the true relative risk. A reference level (RL) of 8.8 μg/m3 was applied. We then used the RR estimates and county-level PTB prevalence to quantify PM2.5-attributable PTB. Direct medical costs were obtained from the 2007 Institute of Medicine report, and lost economic productivity (LEP) was estimated using a meta-analysis of PTB-associated IQ loss, and well-established relationships of IQ loss with LEP. All costs were calculated using 2010 dollars. An estimated 3.32% of PTBs nationally (corresponding to 15,808 PTBs) in 2010 could be attributed to PM2.5 (PM2.5 > 8.8 μg/m3). Attributable PTBs cost were estimated at $5.09 billion [sensitivity analysis (SA): $2.43-9.66 B], of which $760 million were spent for medical care (SA: $362 M-1.44 B). The estimated PM2.5 attributable fraction (AF) of PTB was highest in urban counties, with highest AFs in the Ohio Valley and the southern United States. PM2.5 may contribute substantially to burden and costs of PTB in the United States, and considerable health and economic benefits could be achieved through environmental regulatory interventions that reduce PM2.5 exposure in pregnancy. Citation: Trasande L, Malecha P, Attina TM. 2016. Particulate matter exposure and preterm birth: estimates of U.S. attributable burden and economic costs. Environ Health Perspect 124:1913-1918; http://dx.doi.org/10.1289/ehp.1510810.

Folic acid supplementation and preterm birth: results from observational studies.

PubMed

Mantovani, Elena; Filippini, Francesca; Bortolus, Renata; Franchi, Massimo

2014-01-01

Folic acid (FA) supplementation is recommended worldwide in the periconceptional period for the prevention of neural tube defects. Due to its involvement in a number of cellular processes, its role in other pregnancy outcomes such as miscarriage, recurrent miscarriage, low birth weight, preterm birth (PTB), preeclampsia, abruptio placentae, and stillbirth has been investigated. PTB is a leading cause of perinatal mortality and morbidity; therefore its association with FA supplementation is of major interest. The analysis of a small number of randomized clinical trials (RCTs) has not found a beneficial role of FA in reducing the rate of PTBs. The aim of this review was to examine the results from recent observational studies about the effect of FA supplementation on PTB. We carried out a search on Medline and by manual search of the observational studies from 2009 onwards that analyzed the rate of PTB in patients who received supplementation with FA before and/or throughout pregnancy. The results from recent observational studies suggest a slight reduction of PTBs that is not consistent with the results from RCTs. Further research is needed to better understand the role of FA supplementation before and during pregnancy in PTB.

A chemosensor for micro- to nano-molar detection of Ag+ and Hg2+ ions in pure aqueous media and its applications in cell imaging.

PubMed

Nandre, Jitendra P; Patil, Samadhan R; Sahoo, Suban K; Pradeep, Chullikkattil P; Churakov, Andrei; Yu, Fabiao; Chen, Lingxin; Redshaw, Carl; Patil, Ashok A; Patil, Umesh D

2017-10-24

The pyridine substituted thiourea derivative PTB-1 was synthesized and characterized by spectroscopic techniques as well as by single crystal X-ray crystallography. The metal ion sensing ability of PTB-1 was explored by various experimental (naked-eye, UV-Vis, fluorescence, mass spectrometry and 1 H NMR spectroscopy) and theoretical (B3LYP/6-31G**/LANL2DZ) methods. PTB-1 exhibited a highly selective naked-eye detectable color change from colorless to dark brown and UV-Vis spectral changes for the detection of Ag + with a detection limit of 3.67 μM in aqueous medium. The detection of Ag + ions was achieved by test paper strip and supported silica methods. In contrast, PTB-1 exhibited a 23-fold enhanced emission at 420 nm in the presence of Hg 2+ ions with a nano-molar detection limit of 0.69 nM. Finally, the sensor PTB-1 was applied successfully for the intracellular detection of Hg 2+ ions in a HepG2 liver cell line, which was monitored by the use of confocal imaging techniques.

Effectiveness of elective cervical cerclage according to obstetric history.

PubMed

Korb, D; Marzouk, P; Deu, J; Oury, J-F; Sibony, O

2017-01-01

To assess the effectiveness of elective history-indicated cervical cerclage according to obstetrical history. We analyzed pregnancy outcome of a retrospective cohort of women who have had history-indicated McDonald's cerclage. Principal outcome was gestational age (GA) at delivery. Between January 2003 and December 2013, 205 women were included. We analyzed population in two risk groups: 1- Low-risk (≤2 prior preterm birth (PTB)/second trimester loss (STL), or prior success of cerclage), 2- High risk (≥3 prior PTB/STL, or prior failure of cerclage). In the high-risk group, there was a higher frequency of deliveries before 37 weeks (47.5% vs. 24.5%, P=0.001, OR=2.79, 95% CI [1.49-5.23]). Fifty percent of women (n=6/12) delivered before 37 weeks in case of three or more prior PTB/STL, and 51% (n=24/47) in case of prior failure of cervical cerclage. Elective cervical cerclage may be indicated for women with≤2 prior PTB/STL, or prior successful cerclage. For women with≥3 prior PTB/STL, trachelorraphy or cervico-isthmic cerclage could be possible alternatives to cervical cerclage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Decomposition Analysis of Black–White Disparities in Birth Outcomes: The Relative Contribution of Air Pollution and Social Factors in California

PubMed Central

Huang, Jonathan; Basu, Rupa; Wu, Jun; Bruckner, Tim A.

2017-01-01

Background: Racial/ethnic disparities in preterm birth (PTB) are well documented in the epidemiological literature, but little is known about the relative contribution of different social and environmental determinants of such disparities in birth outcome. Furthermore, increased focus has recently turned toward modifiable aspects of the environment, including physical characteristics, such as neighborhood air pollution, to reduce disparities in birth outcomes. Objectives: To apply decomposition methods to understand disparities in preterm birth (PTB) prevalence between births of non-Hispanic black individuals and births of non-Hispanic white individuals in California, according to individual demographics, neighborhood socioeconomic environment, and neighborhood air pollution. Methods: We used all live singleton births in California spanning 2005 to 2010 and estimated PTBs and other adverse birth outcomes for infants borne by non-Hispanic black mothers and white mothers. To compare individual-level, neighborhood-level, and air pollution [Particulate Matter, 2.5 micrometers or less (PM2.5) and nitrogen dioxide (NO2)] predictors, we conducted a nonlinear extension of the Blinder–Oaxaca method to decompose racial/ethnic disparities in PTB. Results: The predicted differences in probability of PTB between black and white infants was 0.056 (95% CI: 0.054, 0.058). All included predictors explained 37.8% of the black–white disparity. Overall, individual (17.5% for PTB) and neighborhood-level variables (16.1% for PTB) explained a greater proportion of the black–white difference in birth outcomes than air pollution (5.7% for PTB). Conclusions: Our results suggest that, although the role of individual and neighborhood factors remains prevailing in explaining black–white differences in birth outcomes, the individual contribution of PM2.5 is comparable in magnitude to any single individual- or neighborhood-level factor. https://doi.org/10.1289/EHP490 PMID:28977781

Silent changes of tuberculosis in Iran (2005-2015): A joinpoint regression analysis.

PubMed

Marvi, Abolfazl; Asadi-Aliabadi, Mehran; Darabi, Mehdi; Rostami-Maskopaee, Fereshteh; Siamian, Hasan; Abedi, Ghasem

2017-01-01

Tuberculosis (TB) poses a severe risk to public health through the world but excessively distresses low-income nations. The aim of this study is to analyze silent changes of TB in Iran (2005-2015): A joinpoint regression analysis. This is a trend study conducted on all patients ( n = 70) that register in control disease center of Joibar (one of coastal cities and tourism destination in Northern Iran which was recognized as an independent town since 1998) during 2005-2015. The characteristics of patients imported to the SPSS 19 and variation in incidence rate of different forms of pulmonary TB (PTB) (PTB+ or PTB-) and extra-PTB (EPTB)/year was analyzed. Variation in incidence rate of TB for male and female groups and different age groups (0-14, 15-24, 25-34, 35-44, 45-54, 55-64, and above 65 years) was analyzed, variation in trend of this diseases for different groups was compared in intended years, and also, variation in incidence rate of TB was analyzed by Joinpoint Regression Software. The total number of TB was 70 cases during 2005-2015. The mean age of patients was 42.31 ± 21.26 years and median age was 40 years. About 71.4% of patients were PTB (55.7% for with PTB+ and 15.7% with PTB-) and rest of them (28.4%) were EPTB. In regard to classification of cases, 97.1% of them were new cases, 1.45% of them were relapsed cases, and 1.45% of them imported cases. In addition, history of hospitalization due to TB was observed in 44.3%. Despite recent developments of governmental health-care system in Iran and proper access to it and considering this fact that identification of TB cases with passive surveillance is possible. Hence, developing certain programs for sensitization of the covered population is essential.

Risk of spontaneous preterm birth in relation to maternal experience of serious life events during pregnancy

PubMed Central

Barrios, Yasmin V; Sanchez, Sixto E; Qiu, Chunfang; Gelaye, Bizu; Williams, Michelle A

2014-01-01

Background The purpose of this study was to examine the risk of preterm birth (PTB) in relation to serious life events experienced during pregnancy in Peruvian women. Methods This case-control study included 479 PTB cases and 480 term controls. In-person interviews asked information regarding sociodemographics, medical and reproductive histories, and serious life events experienced during pregnancy. Multivariate logistic regression procedures were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results Compared with women who did not experience a serious life event during pregnancy, those who experienced the following life events had a more than two-fold increased odds of PTB: death of first-degree relative (adjusted OR 2.10; 95% CI 1.38–3.20), divorce or separation (adjusted OR 2.09; 95% CI 1.10–4.00), financial troubles (adjusted OR 2.70; 95% CI 1.85–3.94), or serious fight with partner (adjusted OR 2.40; 95% CI 1.78–3.17). Women who experienced any serious life events during pregnancy had higher odds (adjusted OR 2.29; 95% CI 1.65–3.18) of suffering spontaneous preterm labor and preterm premature rupture of membranes (adjusted OR 2.19; 95% CI 1.56–3.08), compared with women who did not experience any such events. Associations of similar directions and extent were observed for severity of PTB (ie, very, moderate, or late PTB). The magnitude of the associations increased as increased frequency of serious life events (Ptrend <0.001). Conclusion Experiencing serious life events during pregnancy was associated with increased odds of PTB among Peruvian women. Interventions aimed at assisting women experiencing serious life events may reduce the risk of PTB. Future studies should include objective measures of stress and stress response to understand better the biological underpinnings of these associations. PMID:24591850

Drilling and Production Activity Related to Unconventional Gas Development and Severity of Preterm Birth.

PubMed

Walker Whitworth, Kristina; Kaye Marshall, Amanda; Symanski, Elaine

2018-03-20

Studies of unconventional gas development (UGD) and preterm birth (PTB) have not presented risk estimates by well development phase or trimester. We examined phase and trimester-specific associations between UGD activity and PTB. We conducted a case-control study of women with singleton births in the Barnett Shale area, Texas, from 30 November 2010 to 29 November 2012. We individually age- and race/ethnicity-matched five controls to each PTB case ( n =13,328) and truncated controls' time at risk according to the matched case's gestational age. We created phase-specific UGD-activity metrics: a ) inverse squared distance-weighted (IDW) count of wells in the drilling phase ≤0.5 mi (804.7 meters) of the residence and b ) IDW sum of natural gas produced ≤0.5 mi of the residence. We also constructed trimester- and gestation-specific metrics. Metrics were categorized as follows: zero wells (reference), first, second, third tertiles of UGD activity. Analyses were repeated by PTB severity: extreme, very, and moderate (<28, 28 to<32, and 32 to<37 completed weeks). Data were analyzed using conditional logistic regression. We found increased odds of PTB in the third tertile of the UGD drilling {odds ratio (OR)=1.20 [95% confidence interval (CI): 1.06, 1.37]} and UGD-production [OR=1.15 (1.05, 1.26)] metrics. Among women in the third tertile of UGD-production, associations were strongest in trimesters one [OR=1.18 (1.02, 1.37)] and two [OR=1.14 (0.99, 1.31). The greatest risk was observed for extremely PTB [third tertile ORs: UGD drilling, 2.00 (1.23, 3.24); UGD production, 1.53 (1.03-2.27)]. We found evidence of differences in phase- and trimester-specific associations of UGD and PTB and indication of particular risk associated with extremely preterm birth. Future studies should focus on quantifying specific chemical and nonchemical stressors associated with UGD. https://doi.org/10.1289/EHP2622.

Early Preterm Birth Across Generations Among Whites and African-Americans: A Population-Based Study.

PubMed

Dorner, Rebecca A; Rankin, Kristin M; Collins, James W

2017-11-01

Objectives To determine the extent to which non-Latina White and African-American mother's gestational age is associated with extremely early (<30 weeks), modestly early (30-33 weeks), and late (34-36 weeks) infant preterm birth (PTB) rates. Methods Race-specific stratified and multivariable logistic regression analyses were performed on the Illinois Transgenerational Birth File of non-Latino White and African-American infants (born 1989-1991) and their mothers (born 1956-1976). Results White mothers (n = 184) born at <30 weeks had a greater extremely early infant PTB rate than White mothers (n = 131,980) born at term: 1.6 versus 0.5%, respectively; RR = 3.6 (1.2, 11.0). African-American mothers (n = 269) born at <30 weeks had a greater extremely early infant PTB rate than African-American mothers (n = 34,885) born at term: 4.1 versus 2.1%, respectively; RR = 2.0 (1.1, 3.6). In logistic regression models the adjusted (controlling for maternal age, education, parity, prenatal care, marital status, and cigarette smoking) OR of extremely early PTB for White and African-American mothers born <30 (compared to ≥37) weeks equaled 4.0 (1.2, 12.6) and 2.3 (1.2, 4.3), respectively. The adjusted OR of modestly early PTB for White and African-American mothers born 30-33 (compared to ≥37) weeks equaled 1.6 (1.0, 2.5) and 1.3 (0.9, 1.7), respectively. The adjusted OR of late PTB for White and African-American mothers born 34-36 (compared to ≥37) weeks equaled 1.2 (1.0, 1.3) and 1.1 (1.0, 1.2), respectively. Conclusions A generational association of extremely early, but not modestly early or late, PTB exists among non-Latino Whites and African-Americans.

Concomitant preterm birth and severe small-for-gestational age birth weight among infants of immigrant mothers in Ontario originating from the Philippines and East Asia: a population-based study.

PubMed

Bartsch, Emily; Park, Alison L; Jairam, Jennifer; Ray, Joel G

2017-07-18

Women from the Philippines form one of the largest immigrant groups to North America. Their newborns experience higher rates of preterm birth (PTB), and separately, small-for-gestational age (SGA) birth weight, compared with other East Asians. It is not known if Filipino women are at elevated risk of concomitant PTB and severe SGA (PTB-SGA), a pathological state likely reflective of placental dysfunction and neonatal morbidity. We conducted a population-based study of all singleton or twin live births in Ontario, from 2002 to 2011, among immigrant mothers from the Philippines (n=27 946), Vietnam (n=15 297), Hong Kong (n=5618), South Korea (n=5148) and China (n=42 517). We used modified Poisson regression to generate relative risks (RR) of PTB-SGA, defined as a birth <37 weeks' gestation and a birth weight <5th percentile. RRs were adjusted for maternal age, parity, marital status, income quintile, infant sex and twin births. Relative to mothers from China (2.3 per 1000), the rate of PTB-SGA was significantly higher among infants of mothers from the Philippines (6.5 per 1000; RR 2.91, 95% CI 2.27 to 3.73), and those from Vietnam (3.7 per 1000; RR 1.68, 95% CI 1.21 to 2.34). The RR of PTB-SGA was not higher for infants of mothers from Hong Kong or South Korea. Among infants born to immigrant women from five East Asian birthplaces, the risk of PTB-SGA was highest among those from the Philippines. These women and their fetuses may require additional monitoring and interventions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

DNA Methylation: An Epigenetic Risk Factor in Preterm Birth

PubMed Central

Menon, Ramkumar; Conneely, Karen N.; Smith, Alicia K.

2012-01-01

Spontaneous preterm birth (PTB; birth prior to 37 weeks of gestation) is a complex phenotype with multiple risk factors that complicate our understanding of its etiology. A number of recent studies have supported the hypothesis that epigenetic modifications such as DNA methylation induced by pregnancy-related risk factors may influence the risk of PTB or result in changes that predispose a neonate to adult-onset diseases. The critical role of timing of gene expression in the etiology of PTB makes it a highly relevant disorder in which to examine the potential role of epigenetic changes. Because changes in DNA methylation patterns can result in long-term consequences, it is of critical interest to identify the epigenetic patterns associated with adverse pregnancy outcomes. This review examines the potential role of DNA methylation as a risk factor for PTB and discusses several issues and limitations that should be considered when planning DNA methylation studies. PMID:22228737

Natural variation in PTB1 regulates rice seed setting rate by controlling pollen tube growth.

PubMed

Li, Shuangcheng; Li, Wenbo; Huang, Bin; Cao, Xuemei; Zhou, Xingyu; Ye, Shumei; Li, Chengbo; Gao, Fengyan; Zou, Ting; Xie, Kailong; Ren, Yun; Ai, Peng; Tang, Yangfan; Li, Xuemei; Deng, Qiming; Wang, Shiquan; Zheng, Aiping; Zhu, Jun; Liu, Huainian; Wang, Lingxia; Li, Ping

2013-01-01

Grain number, panicle seed setting rate, panicle number and grain weight are the most important components of rice grain yield. To date, several genes related to grain weight, grain number and panicle number have been described in rice. However, no genes regulating the panicle seed setting rate have been functionally characterized. Here we show that the domestication-related POLLEN TUBE BLOCKED 1 (PTB1), a RING-type E3 ubiquitin ligase, positively regulates the rice panicle seed setting rate by promoting pollen tube growth. The natural variation in expression of PTB1 which is affected by the promoter haplotype and the environmental temperature, correlates with the rice panicle seed setting rate. Our results support the hypothesis that PTB1 is an important maternal sporophytic factor of pollen tube growth and a key modulator of the rice panicle seed setting rate. This finding has implications for the improvement of rice yield.

Worry about racial discrimination: A missing piece of the puzzle of Black-White disparities in preterm birth?

PubMed

Braveman, Paula; Heck, Katherine; Egerter, Susan; Dominguez, Tyan Parker; Rinki, Christine; Marchi, Kristen S; Curtis, Michael

2017-01-01

The causes of the large and persistent Black-White disparity in preterm birth (PTB) are unknown. It is biologically plausible that chronic stress across a woman's life course could be a contributor. Prior research suggests that chronic worry about experiencing racial discrimination could affect PTB through neuroendocrine, vascular, or immune mechanisms involved in both responses to stress and the initiation of labor. This study aimed to examine the role of chronic worry about racial discrimination in Black-White disparities in PTB. The data source was cross-sectional California statewide-representative surveys of 2,201 Black and 8,122 White, non-Latino, U.S.-born postpartum women with singleton live births during 2011-2014. Chronic worry about racial discrimination (chronic worry) was defined as responses of "very often" or "somewhat often" (vs. "not very often" or "never") to the question: "Overall during your life until now, how often have you worried that you might be treated or viewed unfairly because of your race or ethnic group?" Prevalence ratios (PRs) with 95% Confidence Intervals (CI) were calculated from sequential logistic regression models, before and after adjustment for multiple social/demographic, behavioral, and medical factors, to estimate the magnitude of: (a) PTB risks associated with chronic worry among Black women and among White women; and (b) Black-White disparities in PTB, before and after adjustment for chronic worry. Among Black and White women respectively, 36.9 (95% CI 32.9-40.9) % and 5.5 (95% CI 4.5-6.5) % reported chronic worry about racial discrimination; rates were highest among Black women of higher income and education levels. Chronic worry was significantly associated with PTB among Black women before (PR 1.73, 95% CI 1.12-2.67) and after (PR 2.00, 95% CI 1.33-3.01) adjustment for covariates. The unadjusted Black-White disparity in PTB (PR 1.59, 95%CI 1.21-2.09) appeared attenuated and became non-significant after adjustment for chronic worry (PR 1.30, 95% CI 0.93-1.81); it appeared further attenuated after adding the covariates (PR 1.17, 95% CI 0.85-1.63). Chronic worry about racial discrimination may play an important role in Black-White disparities in PTB and may help explain the puzzling and repeatedly observed greater PTB disparities among more socioeconomically-advantaged women. Although the single measure of experiences of racial discrimination used in this study precluded examination of the role of other experiences of racial discrimination, such as overt incidents, it is likely that our findings reflect an association between one or more experiences of racial discrimination and PTB. Further research should examine a range of experiences of racial discrimination, including not only chronic worry but other psychological and emotional states and both subtle and overt incidents as well. These dramatic results from a large statewide-representative study add to a growing-but not widely known-literature linking racism-related stress with physical health in general, and shed light on the links between racism-related stress and PTB specifically. Without being causally definitive, this study's findings should stimulate further research and heighten awareness of the potential role of unmeasured social variables, such as diverse experiences of racial discrimination, in racial disparities in health.

Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy.

PubMed

Donders, G G; Van Calsteren, K; Bellen, G; Reybrouck, R; Van den Bosch, T; Riphagen, I; Van Lierde, S

2009-09-01

Abnormal vaginal flora (AVF) before 14 gestational weeks is a risk factor for preterm birth (PTB). The presence of aerobic microorganisms and an inflammatory response in the vagina may also be important risk factors. The primary aim of the study was to investigate the differential influences of AVF, full and partial bacterial vaginosis, and aerobic vaginitis in the first trimester on PTB rate. The secondary aim was to elucidate why treatment with metronidazole has not been found to be beneficial in previous studies. Unselected women with low-risk pregnancies attending the prenatal unit of the Heilig Hart General Hospital in Tienen, Belgium, were included in the study. At the first prenatal visit, 1026 women were invited to undergo sampling of the vaginal fluid for wet mount microscopy and culture, of whom 759 were fully evaluable. Abnormal vaginal flora (AVF; disappearance of lactobacilli), bacterial vaginosis (BV), aerobic vaginitis (AV), increased inflammation (more than ten leucocytes per epithelial cell) and vaginal colonisation with Candida (CV) were scored according to standardised definitions. Partial BV was defined as patchy streaks of BV flora or sporadic clue cells mixed with other flora, and full BV as a granular anaerobic-type flora or more than 20% clue cells. Vaginal fluid was cultured for aerobic bacteria, Mycoplasma hominis and Ureaplasma urealyticum. Outcome was recorded as miscarriage

Worry about racial discrimination: A missing piece of the puzzle of Black-White disparities in preterm birth?

PubMed Central

Braveman, Paula; Heck, Katherine; Rinki, Christine; Curtis, Michael

2017-01-01

Objectives The causes of the large and persistent Black-White disparity in preterm birth (PTB) are unknown. It is biologically plausible that chronic stress across a woman’s life course could be a contributor. Prior research suggests that chronic worry about experiencing racial discrimination could affect PTB through neuroendocrine, vascular, or immune mechanisms involved in both responses to stress and the initiation of labor. This study aimed to examine the role of chronic worry about racial discrimination in Black-White disparities in PTB. Methods The data source was cross-sectional California statewide-representative surveys of 2,201 Black and 8,122 White, non-Latino, U.S.-born postpartum women with singleton live births during 2011–2014. Chronic worry about racial discrimination (chronic worry) was defined as responses of “very often” or “somewhat often” (vs. “not very often” or “never”) to the question: “Overall during your life until now, how often have you worried that you might be treated or viewed unfairly because of your race or ethnic group?” Prevalence ratios (PRs) with 95% Confidence Intervals (CI) were calculated from sequential logistic regression models, before and after adjustment for multiple social/demographic, behavioral, and medical factors, to estimate the magnitude of: (a) PTB risks associated with chronic worry among Black women and among White women; and (b) Black-White disparities in PTB, before and after adjustment for chronic worry. Results Among Black and White women respectively, 36.9 (95% CI 32.9–40.9) % and 5.5 (95% CI 4.5–6.5) % reported chronic worry about racial discrimination; rates were highest among Black women of higher income and education levels. Chronic worry was significantly associated with PTB among Black women before (PR 1.73, 95% CI 1.12–2.67) and after (PR 2.00, 95% CI 1.33–3.01) adjustment for covariates. The unadjusted Black-White disparity in PTB (PR 1.59, 95%CI 1.21–2.09) appeared attenuated and became non-significant after adjustment for chronic worry (PR 1.30, 95% CI 0.93–1.81); it appeared further attenuated after adding the covariates (PR 1.17, 95% CI 0.85–1.63). Conclusions Chronic worry about racial discrimination may play an important role in Black-White disparities in PTB and may help explain the puzzling and repeatedly observed greater PTB disparities among more socioeconomically-advantaged women. Although the single measure of experiences of racial discrimination used in this study precluded examination of the role of other experiences of racial discrimination, such as overt incidents, it is likely that our findings reflect an association between one or more experiences of racial discrimination and PTB. Further research should examine a range of experiences of racial discrimination, including not only chronic worry but other psychological and emotional states and both subtle and overt incidents as well. These dramatic results from a large statewide-representative study add to a growing—but not widely known—literature linking racism-related stress with physical health in general, and shed light on the links between racism-related stress and PTB specifically. Without being causally definitive, this study’s findings should stimulate further research and heighten awareness of the potential role of unmeasured social variables, such as diverse experiences of racial discrimination, in racial disparities in health. PMID:29020025

Estimated Number of Preterm Births and Low Birth Weight Children Born in the United States Due to Maternal Binge Drinking

PubMed Central

Truong, Khoa D; Reifsnider, Odette S; Mayorga, Maria E; Spitler, Hugh

2013-01-01

Objective To estimate the aggregate burden of maternal binge drinking on preterm birth (PTB) and low birth weight (LBW) across American sociodemographic groups in 2008. Methods A simulation model was developed to estimate the number of PTB and LBW cases due to maternal binge drinking. Data inputs for the model included number of births and rates of preterm and LBW from the National Center for Health Statistics; female population by childbearing age groups from the U.S. Census; increased relative risks of preterm and LBW deliveries due to maternal binge drinking extracted from the literature; and adjusted prevalence of binge drinking among pregnant women estimated in a multivariate logistic regression model using Behavioral Risk Factor Surveillance System survey. Results The most conservative estimates attributed maternal binge drinking to 8,701 (95% CI: 7,804–9,598) PTBs (1.75% of all PTBs) and 5,627 (95% CI 5,121–6,133) LBW deliveries in 2008, with 3,708 (95% CI: 3,375–4,041) cases of both PTB and LBW. The estimated rate of PTB due to maternal binge drinking was 1.57% among all PTBs to White women, 0.69% among Black women, 3.31% among Hispanic women, and 2.35% among other races. Compared to other age groups, women ages 40–44 had the highest adjusted binge drinking rate and highest PTB rate due to maternal binge drinking (4.33%). Conclusion Maternal binge drinking contributed significantly to PTB and LBW differentially across sociodemographic groups. PMID:22711260

Women with preterm birth have a distinct cervicovaginal metabolome.

PubMed

Ghartey, Jeny; Bastek, Jamie A; Brown, Amy G; Anglim, Laura; Elovitz, Michal A

2015-06-01

Metabolomics has the potential to reveal novel pathways involved in the pathogenesis of preterm birth (PTB). The objective of this study was to investigate whether the cervicovaginal (CV) metabolome was different in asymptomatic women destined to have a PTB compared with term birth. A nested case-control study was performed using CV fluid collected from a larger prospective cohort. The CV fluid was collected between 20-24 weeks (V1) and 24-28 weeks (V2). The metabolome was compared between women with a spontaneous PTB (n = 10) to women who delivered at term (n = 10). Samples were extracted and prepared for analysis using a standard extraction solvent method. Global biochemical profiles were determined using gas chromatography/mass spectrometry and ultra-performance liquid chromatography/tandem mass spectrometry. An ANOVA was used to detect differences in biochemical compounds between the groups. A false discovery rate was estimated to account for multiple comparisons. A total of 313 biochemicals were identified in CV fluid. Eighty-two biochemicals were different in the CV fluid at V1 in those destined to have a PTB compared with term birth, whereas 48 were different at V2. Amino acid, carbohydrate, and peptide metabolites were distinct between women with and without PTB. These data suggest that the CV space is metabolically active during pregnancy. Changes in the CV metabolome may be observed weeks, if not months, prior to any clinical symptoms. Understanding the CV metabolome may hold promise for unraveling the pathogenesis of PTB and may provide novel biomarkers to identify women most at risk. Copyright © 2015 Elsevier Inc. All rights reserved.

Variation in Birth Outcomes by Mother’s Country of Birth Among Non-Hispanic Black Women in the United States

PubMed Central

Vang, Zoua; Culhane, Jennifer F.

2014-01-01

Rates of prematurity (PTB) and small-for-gestational age (SGA) were compared between US-born and foreign-born non-Hispanic black women. Comparisons were also made between Sub-Saharan African-born and Caribbean-born black women and by maternal country of birth within the two regions. Comparisons were adjusted for sociodemographic, health behavioral and medical risk factors available on the birth record. Birth record data (2008) from all states (n = 27) where mother’s country of birth was recorded were used. These data comprised 58 % of all singleton births to non-Hispanic black women in that year. Pearson Chi square and logistic regression were used to investigate variation in the rates of PTB and SGA by maternal nativity. Foreign-born non-Hispanic black women had significantly lower rates of PTB (OR 0.727; CI 0. 726, 0.727) and SGA (OR 0.742; CI 0.739–0.745) compared to US-born non-Hispanic black women in a fully adjusted model. Sub-Saharan African-born black women compared to Caribbean-born black women had significantly lower rates of PTB and SGA. Within each region, the rates of PTB and SGA varied by mother’s country of birth. These differences could not be explained by adjustment for known risk factors obtained from vital records. Considerable heterogeneity in rates of PTB and SGA among non-Hispanic black women in the US by maternal nativity was documented and remained unexplained after adjustment for known risk factors. PMID:24756226

Interaction of maternal smoking and preterm birth on future risk of maternal cardiovascular disease: A population-based record linkage study.

PubMed

Ngo, Anh D; Roberts, Christine L; Chen, Jian S; Figtree, Gemma

2016-04-01

While associations of smoking and preterm birth (PTB) with maternal cardiovascular disease (CVD) risks have been established, it is unknown whether the coexistence of these two conditions could synergistically increase the risks. We linked birth records of 902,008 mothers with singleton infants during 1994-2011 in New South Wales, Australia to the mothers' subsequent CVD hospitalisation or death. Multiplicative interaction was tested through an interaction term in a multivariate Cox-proportional hazard regression model, while additive interaction was assessed by calculating the synergy index. Relative to never-smokers with term babies, the CVD risk in ever-smokers with PTBs (hazard ratio (HR) 3.35, 95% confidence interval (CI) 2.96-3.80) was significantly greater than the sum of risks in ever-smokers with term babies (HR 2.10, 95% CI 1.96-2.24) and in never-smokers with PTBs (HR 1.73, 95% CI 1.55-1.93), indicating an additive interaction (synergy index = 1.29, 95% CI 1.05-1.58). In ever-smokers, the association was stronger for extremely PTB (HR 3.83, 95% CI 3.23-4.69) than moderately PTB (HR 3.18, 95% CI 2.76-3.66), and for ≥2 PTB (HR 4.47, 95% CI 3.39-5.88) than one PTB (HR 3.20, 95% CI 2.81-3.64). Maternal smoking and PTB interact on the additive scale to synergistically increase maternal CVD risks. The interaction was dose-dependent according to both the severity and number of PTBs. © The European Society of Cardiology 2015.

Risk factors for false-negative T-SPOT.TB assay results in patients with pulmonary and extra-pulmonary TB.

PubMed

Pan, Liping; Jia, Hongyan; Liu, Fei; Sun, Huishan; Gao, Mengqiu; Du, Fengjiao; Xing, Aiying; Du, Boping; Sun, Qi; Wei, Rongrong; Gu, Shuxiang; Zhang, Zongde

2015-04-01

To investigate the risk factors for false-negative T-SPOT.TB results in patients with pulmonary TB (PTB) and extra-pulmonary TB (EPTB). Patients with suspected TB who underwent valid T-SPOT.TB tests were prospectively enrolled at Beijing Chest Hospital between November 2012 and November 2013. Basic characters and clinical laboratory findings were compared between true-positive and false-negative T-SPOT.TB groups. Of 1928 suspected TB patients, 774 (530 PTB and 244 EPTB) microbiologically/histopathogenically-confirmed patients (636 culture-confirmed) were analyzed. Forty-six PTB patients (8.7%) and 32 EPTB patients (13.1%) had negative T-SPOT.TB results. Multivariate analysis showed that increased age [odds radio (OR) 2.26, 95% confidence interval (CI) 1.11-4.58], over-weight (BMI ≥ 25 kg/m(2), OR 2.43, 95% CI 1.05-5.63), and a longer period of illness before hospitalization (>6 months, OR 2.46, 95% CI 1.24-4.92) were independent risk factors for false-negative T-SPOT.TB results in PTB patients. In EPTB patients, increased age (OR 2.42, 95% CI 1.09-5.35) also showed an independent association with false-negative T-SPOT.TB results. Careful interpretation of negative T-SPOT.TB results is necessary in older patients with suspected PTB or EPTB, and in PTB patients who are over-weight or have had longer periods of illness before hospitalization. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Astronomical timescale calibration for the Permian-Triassic boundary transition interval from global correlation of cyclic marine sequences

NASA Astrophysics Data System (ADS)

Huang, C.; Hinnov, L. A.; Tong, J.; Chen, Z.

2011-12-01

The mass extinctions near the Permian-Triassic boundary (PTB) resulted in the greatest dying of life on Earth. The cause of this catastrophe remains enigmatic. High-resolution chronology is crucial to understanding the recorded pattern of biotic evolution and possible causes for the extinctions. Magnetic susceptibility (MS) data from Shangsi, South China shows evidence for astronomical forcing through the PTB interval, with strong 405-kyr cycling. This allows development of an astrochronology for the PTB interval based on the 405-kyr orbital eccentricity metronome that has been proposed for the Mesozoic timescale. Radioisotope dating combined with the 405-kyr tuned MS series from Shangsi shows that the 405-kyr-cycle predominates throughout the PTB interval. In the Permian segment, ~100-kyr cyclicity dominates, and the 100-kyr-scale MS maxima correlate with high-amplitude precession-scale MS variations. Minima in the ~1.5-Myr, 405-kyr and ~100-kyr cycles converge at 252.6 Ma, approximately 200 kyr before the onset of the main mass extinction near the PTB. In the Triassic aftermath, the recorded astronomical signal is different, with predominant 405-kyr cycles and loss of 100 kyr cyclicity, and appearance of ~33 kyr (obliquity scale) cyclicity; 100-kyr cyclicity strengthens again 2 Myr later. This pattern indicates a change in the response of the depositional environment (or magnetic susceptibility) to astronomical forcing before and after the mass extinction interval. The astrochronology interpolates the timescale between the radioisotopically determined absolute dates; this facilitates estimation of ages for specific events in the PTB crisis, including magnetic reversals, biozone boundaries, and the mass extinctions. An estimated ~700 kyr duration for the Mass Extinction Interval (MEI) at Shangsi based on the 405-kyr tuning is supported by eccentricity-tuned estimates of three other sections in China (Meishan, Huangzhishan, and Heping), and two Alpine sections (Gartnerkofel, Austria and Bulla, Italy) from the eastern and western margins of the Palaeo-Tethys Ocean during PTB time. This suggests that the PTB mass extinctions were not the result of a single catastrophic event. Siberian trap volcanism was largely synchronous with the MEI and appears to be the most likely cause of the mass extinctions; astronomically paced climate change may also have played a role.

The impact of nutritional deficit on mortality of in-patients with pulmonary tuberculosis.

PubMed

Kim, H-J; Lee, C-H; Shin, S; Lee, J H; Kim, Y W; Chung, H S; Han, S K; Shim, Y-S; Kim, D K

2010-01-01

A metropolitan governmental medical centre, Seoul, Republic of Korea. To elucidate the impact of the nutritional deficit assessed by the Nutritional Risk Score (NRS) on the outcomes of in-patients with pulmonary tuberculosis (PTB). All hospitalised patients with microbiologically confirmed PTB were enrolled. A four-point NRS included low body mass index (<18.5 kg/m(2)), hypoalbuminaemia (<30.0 g/l), hypocholesterolaemia (<2.33 mmol/l) and severe lymphocytopaenia (<7 x 10(5) cells/l). The primary outcome was overall in-hospital mortality. The degree of radiographical resolution after anti-tuberculosis treatment was also evaluated. In a total of 156 patients, the male to female ratio was 1.6:1. The overall mortality was 13.5% and tuberculosis-specific fatality was 3.9%. Predisposing factors and high NRS (> or = 3 points) were independent risk factors for in-hospital death after adjusting for the severity of PTB. High NRS (OR = 16.8, P < 0.001) and predisposing factors (OR = 5.4, P = 0.032) were independent risk factors for 30-day survival. The NRS was not associated with radiographic improvement. Regardless of disease severity, the high NRS was a significant negative predictor among in-patients with PTB; this finding should therefore be considered in the management of PTB despite the current era of effective anti-tuberculosis chemotherapy.

Automated microfluidic devices integrating solid-phase extraction, fluorescent labeling, and microchip electrophoresis for preterm birth biomarker analysis.

PubMed

Sahore, Vishal; Sonker, Mukul; Nielsen, Anna V; Knob, Radim; Kumar, Suresh; Woolley, Adam T

2018-01-01

We have developed multichannel integrated microfluidic devices for automated preconcentration, labeling, purification, and separation of preterm birth (PTB) biomarkers. We fabricated multilayer poly(dimethylsiloxane)-cyclic olefin copolymer (PDMS-COC) devices that perform solid-phase extraction (SPE) and microchip electrophoresis (μCE) for automated PTB biomarker analysis. The PDMS control layer had a peristaltic pump and pneumatic valves for flow control, while the PDMS fluidic layer had five input reservoirs connected to microchannels and a μCE system. The COC layers had a reversed-phase octyl methacrylate porous polymer monolith for SPE and fluorescent labeling of PTB biomarkers. We determined μCE conditions for two PTB biomarkers, ferritin (Fer) and corticotropin-releasing factor (CRF). We used these integrated microfluidic devices to preconcentrate and purify off-chip-labeled Fer and CRF in an automated fashion. Finally, we performed a fully automated on-chip analysis of unlabeled PTB biomarkers, involving SPE, labeling, and μCE separation with 1 h total analysis time. These integrated systems have strong potential to be combined with upstream immunoaffinity extraction, offering a compact sample-to-answer biomarker analysis platform. Graphical abstract Pressure-actuated integrated microfluidic devices have been developed for automated solid-phase extraction, fluorescent labeling, and microchip electrophoresis of preterm birth biomarkers.

Evaluation of whole blood IFNgamma test using PPD and recombinant antigen challenge for diagnosis of pulmonary and extra-pulmonary tuberculosis.

PubMed

Kalantri, Yatiraj; Hemvani, Nanda; Chitnis, D S

2009-06-01

Quantiferon TB gold (QFT-G) with recombinant antigen cocktail is well evaluated for diagnosis of pulmonary tuberculosis (PTB). However, diagnosis of extra-pulmonary tuberculosis (EPTB) is more difficult due to limitations of conventional techniques. This study compares recombinant antigens based QFT-G and low cost PPD based interferon test for the diagnosis of PTB and EPTB. IFNgamma release, with recombinant antigens and PPD, was assayed by ELISA from 140 cases of EPTB, 100 cases of PTB along with acid fast bacillus (AFB) detection, AFB culture on LJ and MGIT BACTEC. Sensitivity and specificity for QFT-G recombinant antigens was 84.29% and 96%, while for PPD based interferon was 70% and 84% for EPTB group. The sensitivity was far superior to AFB smear and culture for both the antigens. Nine samples were identified as non-tubercular mycobacteria (NTM) in the EPTB group and all were negative for QFT-G, but six of them were positive for PPD based test. Results of the study show that QFT-G using recombinant antigen is sensitive and specific for both PTB and EPTB diagnosis. The PPD based test is economic and offers comparable performance for PTB and EPTB diagnosis and also useful for diagnosis of NTM.

Higher serum 25-hydroxyvitamin D concentrations are associated with active pulmonary tuberculosis in hospitalised HIV infected patients in a low income tropical setting: a cross sectional study.

PubMed

Musarurwa, Cuthbert; Zijenah, Lynn Sodai; Mhandire, Doreen Zvipo; Bandason, Tsitsi; Mhandire, Kudakwashe; Chipiti, Maria Mary; Munjoma, Marshall Wesley; Mujaji, Witmore Bayayi

2018-05-08

The inherent risk of developing tuberculosis (TB) in HIV- infected individuals is further enhanced by hypovitaminosis D. Interventions that offset HIV-associated immune deterioration potentially arrest disease progression and incidence of opportunistic infections including TB. Despite conflicting reports on association between vitamin D deficiency (VDD) and risk of TB, vitamin D (VD) supplementation remains a promising intervention. We conducted a comparative cross-sectional study on 145 HIV + /pulmonary TB + (PTB) and 139 HIV + /PTB - hospitalised patients to investigate association of vitamin D status and risk of PTB. Stratified random sampling was used to select archived serum specimens from participants enrolled in a randomised controlled trial (RCT) conducted to investigate the impact of using a point-of-care urine lipoarabinomannan strip test for TB diagnosis. PTB status was confirmed using sputum smear microscopy, culture or GeneXpert MTB/RIF. Serum 25-hydroxyvitamin D [25(OH) D] concentrations were assayed by competitive chemiluminescent immunoassay prior to commencement of anti-TB treatment. Effect of VD status on duration of hospital stay and patient outcomes on follow up at 8 weeks were also investigated. Median serum 25(OH) D concentrations were compared using Mann-Whitney test and covariates of serum VD status were assessed using logistic regression analysis. Overall VDD prevalence in the cohort was 40.9% (95% CI: 35.1-46.8). Median serum 25(OH)D concentrations were significantly higher in HIV + /PTB + group (25.3 ng/ml, IQR:18.0-33.7) compared to the HIV + /PTB - group (20.4 ng/ml, IQR:14.6-26.9), p = 0.0003. Patients with serum 25(OH) D concentration ≥ 30 ng/ml were 1.9 times more likely to be PTB + compared to those with serum 25(OH) D concentrations < 30 ng/ml (odds ratio (OR) 1.91; 95% CI 1.1-3.2). PTB-related death was associated with higher odds of having 25(OH) D levels≥30 ng/ml. Age, gender, CD4 + count, combination antiretroviral therapy (cART) status, efavirenz based cART regimen and length of hospital stay were not associated with vitamin D status. The finding of an association between higher serum 25(OH) D concentrations and active PTB and TB-related mortality among hospitalised HIV-infected patients in the present study is at variance with the commonly reported association of hypovitaminosis and susceptibility to TB. Our findings though, are in concordance with a small pool of reports from other settings.

Recognition of AT-Rich DNA Binding Sites by the MogR Repressor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Aimee; Higgins, Darren E.; Panne, Daniel

2009-07-22

The MogR transcriptional repressor of the intracellular pathogen Listeria monocytogenes recognizes AT-rich binding sites in promoters of flagellar genes to downregulate flagellar gene expression during infection. We describe here the 1.8 A resolution crystal structure of MogR bound to the recognition sequence 5' ATTTTTTAAAAAAAT 3' present within the flaA promoter region. Our structure shows that MogR binds as a dimer. Each half-site is recognized in the major groove by a helix-turn-helix motif and in the minor groove by a loop from the symmetry-related molecule, resulting in a 'crossover' binding mode. This oversampling through minor groove interactions is important for specificity.more » The MogR binding site has structural features of A-tract DNA and is bent by approximately 52 degrees away from the dimer. The structure explains how MogR achieves binding specificity in the AT-rich genome of L. monocytogenes and explains the evolutionary conservation of A-tract sequence elements within promoter regions of MogR-regulated flagellar genes.« less

Sequence-specific binding of counterions to B-DNA

PubMed Central

Denisov, Vladimir P.; Halle, Bertil

2000-01-01

Recent studies by x-ray crystallography, NMR, and molecular simulations have suggested that monovalent counterions can penetrate deeply into the minor groove of B form DNA. Such groove-bound ions potentially could play an important role in AT-tract bending and groove narrowing, thereby modulating DNA function in vivo. To address this issue, we report here 23Na magnetic relaxation dispersion measurements on oligonucleotides, including difference experiments with the groove-binding drug netropsin. The exquisite sensitivity of this method to ions in long-lived and intimate association with DNA allows us to detect sequence-specific sodium ion binding in the minor groove AT tract of three B-DNA dodecamers. The sodium ion occupancy is only a few percent, however, and therefore is not likely to contribute importantly to the ensemble of B-DNA structures. We also report results of ion competition experiments, indicating that potassium, rubidium, and cesium ions bind to the minor groove with similarly weak affinity as sodium ions, whereas ammonium ion binding is somewhat stronger. The present findings are discussed in the light of previous NMR and diffraction studies of sequence-specific counterion binding to DNA. PMID:10639130

Specific trans-acting proteins interact with auxiliary RNA polyadenylation elements in the COX-2 3′-UTR

PubMed Central

Hall-Pogar, Tyra; Liang, Songchun; Hague, Lisa K.; Lutz, Carol S.

2007-01-01

Two cyclooxygenase (COX) enzymes, COX-1 and COX-2, are present in human cells. While COX-1 is constitutively expressed, COX-2 is inducible and up-regulated in response to many signals. Since increased transcriptional activity accounts for only part of COX-2 up-regulation, we chose to explore other RNA processing mechanisms in the regulation of this gene. Previously, we showed that COX-2 is regulated by alternative polyadenylation, and that the COX-2 proximal polyadenylation signal contains auxiliary upstream sequence elements (USEs) that are very important in efficient polyadenylation. To explore trans-acting protein factors interacting with these cis-acting RNA elements, we performed pull-down assays with HeLa nuclear extract and biotinylated RNA oligonucleotides representing COX-2 USEs. We identified PSF, p54nrb, PTB, and U1A as proteins specifically bound to the COX-2 USEs. We further explored their participation in polyadenylation using MS2 phage coat protein-MS2 RNA binding site tethering assays, and found that tethering any of these four proteins to the COX-2 USE mutant RNA can compensate for these cis-acting elements. Finally, we suggest that these proteins (p54nrb, PTB, PSF, and U1A) may interact as a complex since immunoprecipitations of the transfected MS2 fusion proteins coprecipitate the other proteins. PMID:17507659

Black-white preterm birth disparity: a marker of inequality

EPA Science Inventory

Purpose. The racial disparity in preterrn birth (PTB) is a persistent feature of perinatal epidemiology, inconsistently modeled in the literature. Rather than include race as an explanatory variable, or employ race-stratified models, we sought to directly model the PTB disparity ...

Vitamin D Receptor ApaI (rs7975232) Polymorphism Confers Decreased Risk of Pulmonary Tuberculosis in Overall and African Population, but not in Asians: Evidence from a Meta-analysis.

PubMed

Areeshi, Mohammed Y; Mandal, Raju K; Wahid, Mohd; Dar, Sajad A; Jawed, Arshad; Lohani, Mohtashim; Abdallah, Amir Mahgoub Awadelkareem; Khan, Saif; Panda, Aditya K; Mishra, B N; Haque, Shafiul

2017-09-01

The involvement of the VDR ApaI gene polymorphism in the development of pulmonary tuberculosis (PTB) has been reported by numerous published studies and yielded inconsistent results. The present meta-analysis evaluated the association of VDR ApaI polymorphism and risk of PTB occurrence. PubMed (Medline), EMBASE and Google Scholar web-databases were searched and a meta-analysis was performed by calculating the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). This meta-analysis included a total of 14 eligible studies comprising of 1958 confirmed PTB cases and 2938 controls. We observed decreased risk of PTB in allelic (a vs. A: p =0.003; OR=0.873, 95% CI=0.798 to 0.955), homozygous (aa vs. AA: p =0.006; OR=0.761, 95% CI=0.626 to 0.924), dominant (aa+Aa vs. AA: p =0.039; OR=0.874, 95% CI=0.769 to 0.993) and recessive (aa vs. AA+Aa: p =0.025; OR=0.819, 95% CI=0.688 to 0.975) genetic models. During subgroup analysis, allele (a vs. A: p =0.005; OR=0.846, 95% CI=0.753 to 0.951), homozygous (aa vs. AA: p =0.002; OR=0.662, 95% CI=0.513 to 0.854) and recessive genetic models (aa vs. AA+Aa: p=0.003; OR=0.709, 95% CI=0.566 to 0.889) demonstrated decreased PTB risk in African population. However, no significant association was observed in Asian population. In conclusion, VDR ApaI polymorphism is significantly associated with decreased risk of PTB for in overall and African population, but not in Asians. © 2017 by the Association of Clinical Scientists, Inc.

Utility of Point-of-care Ultrasound in Children With Pulmonary Tuberculosis.

PubMed

Bélard, Sabine; Heuvelings, Charlotte C; Banderker, Ebrahim; Bateman, Lindy; Heller, Tom; Andronikou, Savvas; Workman, Lesley; Grobusch, Martin P; Zar, Heather J

2018-07-01

Point-of-care ultrasound (POCUS) detects extrapulmonary tuberculosis (EPTB) in HIV infected adults but has not been evaluated in children despite their higher risk of EPTB. This study's aims were to investigate feasibility of POCUS for EPTB in children, frequency of POCUS findings suggestive of EPTB and time to sonographic resolution of findings with treatment. This prospective South African cohort study enrolled children with suspected pulmonary tuberculosis (PTB). POCUS for pleural, pericardial or ascitic effusion, abdominal lymphadenopathy or splenic or hepatic microabscesses was performed and repeated at 1, 3 and 6 months of tuberculosis (TB) treatment. Prevalence of POCUS findings and their association with HIV infection was investigated in children with confirmed PTB (microbiologically proven), unconfirmed PTB (clinically diagnosed) or unlikely TB (respiratory disease that improved during follow-up without TB treatment). Of 232 children [median age 37 months (interquartile range, 18-74)], 39 (17%) were HIV infected. Children with confirmed or unconfirmed PTB had a higher prevalence of POCUS findings than children with unlikely TB [18 of 58 (31%) and 36 of 119 (30%) vs. 8 of 55 (15%); P = 0.04 and P = 0.03, respectively]. Pleural effusion [n = 30 (13%)] or abdominal lymphadenopathy [n = 28 (12%)] were the most common findings; splenic microabscesses [n = 12 (5%)] were strongly associated with confirmed PTB. Children coinfected with HIV and TB were more likely than HIV-uninfected children with TB to have abdominal lymphadenopathy (37% vs. 10%; P < 0.001) or splenic microabscesses (23% vs. 3%; P < 0.001]. Most ultrasound findings were resolved by 3 months with appropriate TB treatment. POCUS for EPTB in children with PTB is feasible. The high prevalence of findings suggests that POCUS can contribute to timely diagnosis of childhood TB and to monitoring treatment response.

Alcohol use disorders among pulmonary tuberculosis patients under RNTCP in urban Pondicherry, India.

PubMed

Veerakumar, A M; Sahu, Swaroop Kumar; Sarkar, Sonali; Kattimani, Shivanand; Govindarajan, S

2015-07-01

Alcohol use is implicated in a wide variety of diseases and disorders including TB. To study the prevalence and pattern of alcohol use among the PTB patients registered under RNTCP in urban Pondicherry and the association of various socio-demographic variables with alcohol drinking during treatment. A cross-sectional study was conducted among 235 PTB patients from 6 randomly selected urban PHCs of Pondicherry from Jan 2013 to March 2014. Alcohol Use Disorder Identification Test (AUDIT) was used for screening the PTB patients for their severity of alcohol use. Data were entered in Epi-data v3.1 and was analyzed by SPSS v20. Chi-square test and multiple-logistic regression were used. Prevalence of alcohol use among PTB patients at the time of diagnosis was 59% and during treatment was 31.5%. Around 54% PTB patients had alcohol use disorders (AUD) during diagnosis, whereas the same during treatment was 26.4%. Among drinkers at the time of diagnosis (n=139), 80% modified and 20% did not modify their alcohol use even after TB diagnosis. Male gender was significantly associated with alcohol use (p≤0.001). Univariate analysis showed that lower level of education, lower SES, unemployed/unskilled/semiskilled/skilled occupational group, and Category II were significantly associated with alcohol use among male patients (p<0.05). Multivariate analysis showed that none of the variables were associated. One-third of PTB patients were drinking alcohol during the treatment. Though 80% modified alcohol use after TB diagnosis, the rest 20% did not modify. Necessary interventions need to be planned to screen for alcohol use. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

pH-Responsive Hydrogel With an Anti-Glycation Agent for Modulating Experimental Periodontitis.

PubMed

Yu, Min-Chen; Chang, Chih-Yeun; Chao, Yi-Chi; Jheng, Yi-Han; Yang, Connie; Lee, Ning; Yu, Shan-Huey; Yu, Xin-Hong; Liu, Dean-Mo; Chang, Po-Chun

2016-06-01

Stimulus-responsive devices have emerged as a novel approach for local drug delivery. This study investigates the feasibility of a novel chitosan-based, pH-responsive hydrogel loaded with N-phenacylthiazolium bromide (PTB), which cleaves the crosslinks of advanced glycation end products on the extracellular matrix. A chitosan-based hydrogel loaded with PTB was fabricated, and the in vitro release profile was evaluated within pH 5.5 to 7.4. BALB/cJ mice and Sprague-Dawley rats were used to evaluate the effects during the induction and recovery phases of periodontitis, respectively, and animals in each phase were divided into four groups: 1) no periodontitis induction; 2) ligature-induced experimental periodontitis (group PR); 3) experimental periodontitis plus hydrogel without PTB (group PH); and 4) experimental periodontitis plus hydrogel with PTB (group PP). The therapeutic effects were evaluated by microcomputed tomographic imaging of periodontal bone level (PBL) loss and histomorphometry for inflammatory cell infiltration and collagen density. PTB was released faster at pH 5.5 to 6.5 and consistently slower at pH 7.4. In the induction phase, PBL and inflammatory cell infiltration were significantly reduced in group PP relative to group PR, and the loss of collagen matrix was significantly reduced relative to that observed in group PH. In the recovery phase, PBL and inflammatory cell infiltration were significantly reduced, and significantly greater collagen deposition was noted in group PP relative to groups PR and PH at 4 and 14 days after silk removal. Chitosan-based, pH-responsive hydrogels loaded with PTB can retard the initiation of and facilitate the recovery from experimental periodontitis.

Whole Blood Gene Expression Profile Associated with Spontaneous Preterm Birth in Women with Threatened Preterm Labor

PubMed Central

Heng, Yujing Jan; Pennell, Craig Edward; Chua, Hon Nian; Perkins, Jonathan Edward; Lye, Stephen James

2014-01-01

Threatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and is the most common condition that requires hospitalization during pregnancy. Most of these TPTL women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. The aim of this work was to study differential whole blood gene expression associated with spontaneous preterm birth (sPTB) within 48 hours of hospital admission. Peripheral blood was collected at point of hospital admission from 154 women with TPTL before any medical treatment. Microarrays were utilized to investigate differential whole blood gene expression between TPTL women who did (n = 48) or did not have a sPTB (n = 106) within 48 hours of admission. Total leukocyte and neutrophil counts were significantly higher (35% and 41% respectively) in women who had sPTB than women who did not deliver within 48 hours (p<0.001). Fetal fibronectin (fFN) test was performed on 62 women. There was no difference in the urine, vaginal and placental microbiology and histopathology reports between the two groups of women. There were 469 significant differentially expressed genes (FDR<0.05); 28 differentially expressed genes were chosen for microarray validation using qRT-PCR and 20 out of 28 genes were successfully validated (p<0.05). An optimal random forest classifier model to predict sPTB was achieved using the top nine differentially expressed genes coupled with peripheral clinical blood data (sensitivity 70.8%, specificity 75.5%). These differentially expressed genes may further elucidate the underlying mechanisms of sPTB and pave the way for future systems biology studies to predict sPTB. PMID:24828675

Risk of Spontaneous Preterm Birth in Relation to Maternal Exposure to Intimate Partner Violence During Pregnancy in Peru

PubMed Central

Sanchez, Sixto E.; Alva, Andrea V.; Chang, Guillermo Diez; Qiu, Chungfang; Yanez, David; Gelaye, Bizu; Williams, Michelle A.

2012-01-01

Objective Intimate partner violence (IPV) is increasingly recognized as an important cause of maternal and perinatal morbidity. We assessed the relation between IPV and risk of spontaneous preterm birth (PTB) among Peruvian women. Methods The study was conducted among 479 pregnant women who delivered a preterm singleton infant (<37 weeks gestation) and 480 controls (≥37 weeks gestation). Participants’ exposure to physical and emotional violence during pregnancy was collected during in-person interviews conducted after delivery and while patients were in hospital. Odds ratios (aOR) and 95% confidence intervals (CI) were estimated from logistic regression models. Results The prevalence of any IPV during pregnancy was 52.2% among cases and 34.6% among controls. Compared with those reporting no exposure to IPV during pregnancy, women reporting any exposure had a 2.1-fold increased risk of PTB (95% CI 1.59–2.68). The association was attenuated slightly after adjusting for maternal age, pre-pregnancy weight, and other covariates (OR=1.99; 95% CI: 1.52–2.61). Emotional abuse in the absence of physical violence was associated with a 1.6-fold (95% CI 1.21–2.15) increased risk of PTB. Emotional and physical abuse during pregnancy was associated with a 4.7-fold increased risk of PTB (95% CI 2.74–7.92). Associations of similar directions and magnitudes were observed when PTB were sub-categorized according to clinical presentation or severity. Conclusion IPV among pregnant women is common and is associated with an increased risk of PTB. Our findings and those of others support recent calls for coordinated global health efforts to prevent violence against women. PMID:22527763

Shift work, long working hours and preterm birth: a systematic review and meta-analysis.

PubMed

van Melick, M J G J; van Beukering, M D M; Mol, B W; Frings-Dresen, M H W; Hulshof, C T J

2014-11-01

Specific physical activities or working conditions are suspected for increasing the risk of preterm birth (PTB). The aim of this meta-analysis is to review and summarize the pre-existing evidence on the effect of shift work or long working hours on the risk of PTB. We conducted a systematic search in MEDLINE and EMBASE (1990-2013) for observational and intervention studies with original data. We only included articles that met our specific criteria for language, exposure, outcome, data collection and original data that were of at least of moderate quality. The data of the included studies were pooled. Eight high-quality studies and eight moderate-quality studies were included in the meta-analysis. In these studies, no clear or statistically significant relationship between shift work and PTB was found. The summary estimate OR for performing shift work during pregnancy and the risk of PTB were 1.04 (95% CI 0.90-1.20). For long working hours during pregnancy, the summary estimate OR was 1.25 (95% CI 1.01-1.54), indicating a marginally statistically significant relationship but an only slightly elevated risk. Although in many of the included studies a positive association between long working hours and PTB was seen this did reach only marginal statistical significance. In the studies included in this review, working in shifts or in night shifts during pregnancy was not significantly associated with an increased risk for PTB. For both risk factors, due to the lack of high-quality studies focusing on the risks per trimester, in particular the third trimester, a firm conclusion about an association cannot be stated.

Prevalence and risk factors for adult pulmonary tuberculosis in a metropolitan city of South India.

PubMed

Dhanaraj, Baskaran; Papanna, Mohan Kumar; Adinarayanan, Srividya; Vedachalam, Chandrasekaran; Sundaram, Vijayaraj; Shanmugam, Shivakumar; Sekar, Gomathi; Menon, Pradeep Aravindan; Wares, Fraser; Swaminathan, Soumya

2015-01-01

The present study measured the community prevalence and risk factors of adult pulmonary tuberculosis (PTB) in Chennai city, and also studied geographical distribution and the presence of different M. tuberculosis strains in the survey area. A community-based cross sectional survey was carried out from July 2010 to October 2012 in Chennai city. Prevalence of bacteriologically positive PTB was estimated by direct standardization method. Univariate and multivariate analyses were carried out to identify significant risk factors. Drug susceptibility testing and spoligotyping was performed on isolated M. tuberculosis strains. Mapping of PTB cases was done using geographic positioning systems. Of 59,957 eligible people, 55,617 were screened by X-ray and /or TB symptoms and the prevalence of smear, culture, and bacteriologically positive PTB was estimated to be 228 (95% CI 189-265), 259 (95% CI 217-299) and 349 (95% CI 330-428) per 100,000 population, respectively. Prevalence of smear, culture, and bacteriologically positive PTB was highest amongst men aged 55-64 years. Multivariate analysis showed that occurrence of both culture and bacteriologically positive PTB disease was significantly associated with: age >35 years, past history of TB treatment, BMI <18.5 Kgs/m2, solid cooking fuel, and being a male currently consuming alcohol. The most frequent spoligotype family was East African Indian. Spatial distribution showed that a high proportion of patients were clustered in the densely populated north eastern part of the city. Our findings demonstrate that TB is a major public health problem in this urban area of south India, and support the use of intensified case finding in high risk groups. Undernutrition, slum dwelling, indoor air pollution and alcohol intake are modifiable risk factors for TB disease.

Effect of DOTS Treatment on Vitamin D Levels in Pulmonary Tuberculosis.

PubMed

Naik, Akshatha Lalesh; Rajan, Madan Gopal; Manjrekar, Poornima A; Shenoy, Mamatha T; Shreelata, Souparnika; Srikantiah, Rukmini Mysore; Hegde, Anupama

2017-04-01

Vitamin D (Vit D) modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair. Vit D Deficiency (VDD) is been implicated as a cause in diabetes, immune dysfunction and Tuberculosis (TB). Impaired metabolism of Vit D and an adverse outcome is associated with Pulmonary Tuberculosis (PTB). Directly Observed Treatment Short Course (DOTS) consist of drugs like rifampicin and isoniazid, which respectively cause accelerated loss of Vit D due to increased clearance and impairment of 25-hydroxylation causing diminished Vit D action. The aim of the present study was to estimate and compare serum Vit D status in newly diagnosed PTB patients before and after DOTS to validate the supplementation of Vit D in PTB patients. Forty four newly diagnosed PTB patients of both the sexes in the age group of 18 to 60 years before starting DOTS were recruited to participate in this non- randomized controlled trial with their voluntary consent. Vit D status in these patients and the effect of DOTS on Vit D were evaluated. Mean Vit D levels of the study population aged 43±13 years was 20.74 ng/ml (normal >30 ng/ml) at the time of diagnosis. After completion of six months of therapy mean Vit D reduced to 17.49 ng/ml (p-value=0.041). On individual observations, 70% of the participants showed a decrease in Vit D levels from their baseline, whereas 30% showed an increase. Comparison between the two groups indicated the possible role of younger age in the improved status. VDD was seen in PTB patients, which worsened in majority of the study population after treatment; hence it would be advisable to recommend Vit D supplementation in PTB patients for a better outcome.

Use of Mueller matrix polarimetry and optical coherence tomography in the characterization of cervical collagen anisotropy

NASA Astrophysics Data System (ADS)

Chue-Sang, Joseph; Bai, Yuqiang; Stoff, Susan; Gonzalez, Mariacarla; Gomes, Jefferson; Gandjbakhche, Amir; Chernomordik, Viktor V.; Ramella-Roman, Jessica C.

2017-02-01

Preterm birth (PTB) presents a serious medical heath concern throughout the world. There is a high incidence of PTB in both developed and developing countries ranging from 11%-15%, respectively. Studies have shown there may be numerous precursors to PTB including infections, genetic predisposition, nutrition and various other morbidities which all lead to a premature disorganization in the cervical collagen resulting in the weakening of the structure designed to keep the fetus in utero. The changes in cervical collagen orientation and distribution may prove to be a predictor of PTB. Polarization imaging is an effective means to measure optical anisotropy in birefringent materials such as those rich in collagen as the cervix is. Non-invasive, full-field Mueller Matrix polarimetry (MMP) imaging methodologies and ex-vivo second harmonic generation (SHG) imaging were used to assess cervical collagen content and structure in non-pregnant porcine cervices. The SHG microscopy was used to verify the efficacy of the MMP in assessing changes in collagen orientation.

Clinical and epidemiological features of extrapulmonary tuberculosis in a high incidence region.

PubMed

Pérez-Guzmán, Carlos; Vargas, Mario H; Arellano-Macías, María del Rosario; Hernández-Cobos, Silvia; García-Ituarte, Aurea Zelindabeth; Serna-Vela, Francisco Javier

2014-04-01

To describe the clinical features of extrapulmonary tuberculosis (EXPTB) and to evaluate epidemiological data to search for potential explanations for its high frequency in the state of Aguascalientes, Mexico. Clinical records of all patients with tuberculosis seen in Aguascalientes in 2008 were reviewed, and official databases were analyzed. EXPTB comprised 60.5% of the 86 cases evaluated, being lymph nodes the main site affected. Patients with EXPTB were younger and more obese than subjects with pulmonary tuberculosis (PTB). One third of cases in either group had diabetes, a frequency much higher than expected. Epidemiological analysis showed that PTB incidence, but not EXPTB incidence, decreases as geographical altitude increases, and had a descendent trend from 1997 to 2011. The lower frequency of PTB (due to its inverse relationship with altitude and its descendent trend in last years) might explain the high frequency of EXPTB. Obesity appeared to protect against developing pulmonary involvement, and diabetes was more frequent than expected among PTB and EXPTB cases.

From Semi- to Full-Two-Dimensional Conjugated Side-Chain Design: A Way toward Comprehensive Solar Energy Absorption

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chao, Pengjie; Wang, Huan; Qu, Shiwei

Two polymers with fully two-dimensional (2D) conjugated side chains, 2D-PTB-Th and 2D-PTB-TTh, were synthesized and characterized through simultaneously integrating the 2D-TT and the 2D-BDT monomers onto the polymer backbone. Resulting from the synergistic effect from the conjugated side chains on both monomers, the two polymers showed remarkably efficient absorption of the sunlight and improved pi-pi intermolecular interactions for efficient charge carrier transport. The optimized bulk heterojunction device based on 2D-PTB-Th and PC71BM shows a higher PCE of 9.13% compared to PTB7-Th with a PCE of 8.26%, which corresponds to an approximately 10% improvement in solar energy conversion. The fully 2D-conjugatedmore » side-chain concept reported here developed a new molecular design strategy for polymer materials with enhanced sunlight absorption and efficient solar energy conversion.« less

Persisting PET-CT lesion activity and M. tuberculosis mRNA after pulmonary tuberculosis cure

PubMed Central

Malherbe, Stephanus T.; Shenai, Shubhada; Ronacher, Katharina; Loxton, Andre G.; Dolganov, Gregory; Kriel, Magdalena; Van, Tran; Chen, Ray Y.; Warwick, James; Via, Laura E.; Song, Taeksun; Lee, Myungsun; Schoolnik, Gary; Tromp, Gerard; Alland, David; Barry, Clifton E.; Winter, Jill; Walzl, Gerhard

2016-01-01

The absence of a gold standard to determine when antibiotics have induced sterilizing cure confounds the development of new approaches to treat pulmonary tuberculosis (PTB). We detected PET-CT imaging response patterns consistent with active disease along with the presence of Mycobacterium tuberculosis mRNA in sputum and bronchoalveolar lavage samples in a substantial proportion of adult, HIV-negative PTB patients after standard 6-month treatment plus one year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of non-resolving and intensifying lesions on PET-CT might indicate ongoing transcription, suggesting that even apparently curative PTB treatment may not eradicate all organisms in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies and better treatment response markers are likely needed for the successful development of improved and shortened PTB treatment strategies. PMID:27595324

Molecular Characteristics of Mycobacterium tuberculosis Strains Isolated from Cutaneous Tuberculosis Patients in China.

PubMed

Jiang, Haiqin; Jin, Yali; Vissa, Varalakshmi; Zhang, Liangfen; Liu, Weijun; Qin, Lianhua; Wan, Kanglin; Wu, Xiaocui; Wang, Hongsheng; Liu, Weida; Wang, Baoxi

2017-04-06

Cutaneous tuberculosis (CTB) is probably underreported due to difficulties in detection and diagnosis. To address this issue, genotypes of Mycobacterium tuberculosis strains isolated from 30 patients with CTB were mapped at multiple loci, namely, RD105 deletions, spacer oligonucleotides, and Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats (MIRU-VNTRs). Fifty-eight strains of pulmonary tuberculosis (PTB) were mapped as experimental controls. Drug resistance-associated gene mutations were determined by amplicon sequencing of target regions within 7 genes. Beijing family isolates were the most prevalent strains in CTB and PTB. MIRU-VNTR typing separated the Beijing strains from the non-Beijing strains, and the majority of CTB could be separated from PTB counterparts. Drug resistance determining regions showed only one CTB strain expressing isomazid resistance. Thus, while the CTB strains belonged to the same phylogenetic lineages and sub-lineages as the PTB strains, they differed at the level of several MIRU-VNTRs and in the proportion of drug resistance.

Comparison of the NIST and PTB Air-Kerma Standards for Low-Energy X-Rays.

PubMed

O'Brien, Michelle; Bueermann, Ludwig

2009-01-01

A comparison has been made of the air-kerma standards for low-energy x rays at the National Institute of Standards and Technology (NIST) and the Physikalisch-Technische Bundesanstalt (PTB). The comparison involved a series of measurements at the PTB and the NIST using the air-kerma standards and two NIST reference-class transfer ionization chamber standards. Results are presented for the reference radiation beam qualities in the range from 25 kV to 50 kV for low energy x rays, including the techniques used for mammography dose traceability. The tungsten generated reference radiation qualities, between 25 kV and 50 kV used for this comparison, are new to NIST; therefore this comparison will serve as the preliminary comparison for NIST and a verification of the primary standard correction factors. The mammography comparison will repeat two previously unpublished comparisons between PTB and NIST. The results show the standards to be in reasonable agreement within the standard uncertainty of the comparison of about 0.4 %.

Multiple oesophago-respiratory fistulae: sequelae of pulmonary tuberculosis in retroviral infection

PubMed Central

Low, Soo Fin; Ngiu, Chai Soon; Hing, Erica Yee; Abu Bakar, Norzailin

2014-01-01

Pulmonary tuberculosis (PTB) is a common infectious disease worldwide. However, mediastinal tuberculous lymphadenitis complicated by oesophageal involvement and oesophago-respiratory fistula is now uncommon due to improved anti-tuberculous regimes and better general awareness. The overall incidence of acquired oesophago-respiratory fistula due to infection is low, and therefore, the lesion is not often a frontrunner in differential diagnosis. Still, tuberculous oesophago-respiratory fistulae can potentially occur in patients with retroviral disease, as they tend to have atypical and more virulent manifestations. In this study, we report the case of multiple oesophago-respiratory fistulae in a patient with PTB and retroviral disease, and highlight the computed tomography features of these lesions as an atypical presentation of PTB in retroviral disease. Clinicians should suspect oesophago-respiratory fistulae if patients present with Ono’s sign, and remain particularly vigilant for patients with underlying PTB and retroviral disease, as early diagnosis and treatment could help to reduce mortality. PMID:24347038

Quantitative Polymerase Chain Reaction to Assess Response to Treatment of Bacterial Vaginosis and Risk of Preterm Birth.

PubMed

Abramovici, Adi; Lobashevsky, Elena; Cliver, Suzanne P; Edwards, Rodney K; Hauth, John C; Biggio, Joseph R

2015-10-01

The aim of this study was to determine whether quantitative polymerase chain reaction (qPCR) bacterial load measurement is a valid method to assess response to treatment of bacterial vaginosis and risk of preterm birth in pregnant women. Secondary analysis by utilizing stored vaginal samples obtained during a previous randomized controlled trial studying the effect of antibiotics on preterm birth (PTB). All women had risk factors for PTB: (1) positive fetal fibronectin (n=146), (2) bacterial vaginosis (BV) and a prior PTB (n=43), or (3) BV and a prepregnancy weight<50 kg (n=54). Total and several individual BV-related bacteria loads were measured using qPCR for 16S rRNA. Loads were correlated with Nugent scores (Spearman correlation coefficients). Loads were compared pre- and posttreatment with Wilcoxon rank-sum test. Individual patient differences were examined with Wilcoxon signed-rank test. A total of 243 paired vaginal samples were available for analysis: 123 antibiotics and 120 placebo. Groups did not differ by risk factors for PTB. For all samples, bacterial loads were correlated with Nugent score and each of its specific bacterial components (all p<0.01). Baseline total bacterial load did not differ by treatment group (p=0.87). Posttreatment total bacterial load was significantly lower in the antibiotics group than the placebo group (p<0.01). Individual patient total bacterial load decreased significantly posttreatment in the antibiotics group (p<0.01), but not in the placebo group (p=0.12). The rate of PTB did not differ between groups (p=0.24). PTB relative risks calculated for BV positive versus BV negative women and women with the highest quartile total and individual bacterial loads were not statistically significant. qPCR correlates with Nugent score and demonstrates decreased bacterial load after antibiotic treatment. Therefore, it is a valid method of vaginal flora assessment in pregnant women who are at high risk for PTB. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A Polypyrimidine Tract Binding Protein, Pumpkin RBP50, Forms the Basis of a Phloem-Mobile Ribonucleoprotein Complex[W

PubMed Central

Ham, Byung-Kook; Brandom, Jeri L.; Xoconostle-Cázares, Beatriz; Ringgold, Vanessa; Lough, Tony J.; Lucas, William J.

2009-01-01

RNA binding proteins (RBPs) are integral components of ribonucleoprotein (RNP) complexes and play a central role in RNA processing. In plants, some RBPs function in a non-cell-autonomous manner. The angiosperm phloem translocation stream contains a unique population of RBPs, but little is known regarding the nature of the proteins and mRNA species that constitute phloem-mobile RNP complexes. Here, we identified and characterized a 50-kD pumpkin (Cucurbita maxima cv Big Max) phloem RNA binding protein (RBP50) that is evolutionarily related to animal polypyrimidine tract binding proteins. In situ hybridization studies indicated a high level of RBP50 transcripts in companion cells, while immunolocalization experiments detected RBP50 in both companion cells and sieve elements. A comparison of the levels of RBP50 present in vascular bundles and phloem sap indicated that this protein is highly enriched in the phloem sap. Heterografting experiments confirmed that RBP50 is translocated from source to sink tissues. Collectively, these findings established that RBP50 functions as a non-cell-autonomous RBP. Protein overlay, coimmunoprecipitation, and cross-linking experiments identified the phloem proteins and mRNA species that constitute RBP50-based RNP complexes. Gel mobility-shift assays demonstrated that specificity, with respect to the bound mRNA, is established by the polypyrimidine tract binding motifs within such transcripts. We present a model for RBP50-based RNP complexes within the pumpkin phloem translocation stream. PMID:19122103

Interrelationship of Cytokines, Hypothalamic-Pituitary-Adrenal Axis Hormones, and Psychosocial Variables in the Prediction of Preterm Birth

PubMed Central

Pearce, B.D.; Grove, J.; Bonney, E.A.; Bliwise, N.; Dudley, D.J.; Schendel, D.E.; Thorsen, P.

2010-01-01

Background/Aims To examine the relationship of biological mediators (cytokines, stress hormones), psychosocial, obstetric history, and demographic factors in the early prediction of preterm birth (PTB) using a comprehensive logistic regression model incorporating diverse risk factors. Methods In this prospective case-control study, maternal serum biomarkers were quantified at 9–23 weeks’ gestation in 60 women delivering at <37 weeks compared to 123 women delivering at term. Biomarker data were combined with maternal sociodemographic factors and stress data into regression models encompassing 22 preterm risk factors and 1st-order interactions. Results Among individual biomarkers, we found that macrophage migration inhibitory factor (MIF), interleukin-10, C-reactive protein (CRP), and tumor necrosis factor-α were statistically significant predictors of PTB at all cutoff levels tested (75th, 85th, and 90th percentiles). We fit multifactor models for PTB prediction at each biomarker cutoff. Our best models revealed that MIF, CRP, risk-taking behavior, and low educational attainment were consistent predictors of PTB at all biomarker cutoffs. The 75th percentile cutoff yielded the best predicting model with an area under the ROC curve of 0.808 (95% CI 0.743–0.874). Conclusion Our comprehensive models highlight the prominence of behavioral risk factors for PTB and point to MIF as a possible psychobiological mediator. PMID:20160447

Evaluating the diagnostic accuracy of the Xpert MTB/RIF assay on bronchoalveolar lavage fluid: A retrospective study.

PubMed

Lu, Yanjun; Zhu, Yaowu; Shen, Na; Tian, Lei; Sun, Ziyong

2018-02-08

Limited data on the diagnostic accuracy of the Xpert MTB/RIF assay using bronchoalveolar lavage fluid from patients with suspected pulmonary tuberculosis (PTB) have been reported in China. Therefore, a retrospective study was designed to evaluate the diagnostic accuracy of this assay. Clinical, radiological, and microbiological characteristics of 238 patients with suspected PTB were reviewed retrospectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of active PTB were calculated for the Xpert MTB/RIF assay using TB culture or final diagnosis based on clinical and radiological evaluation as the reference standard. The sensitivity and specificity of the Xpert MTB/RIF assay were 84.5% and 98.9%, respectively, and those for smear microscopy were 36.2% and 100%, respectively, when compared to the culture method. However, compared with the sensitivity and specificity of final diagnosis based on clinical and radiological evaluation, the sensitivity and specificity of the assay were 72.9% and 98.7%, respectively, which were significantly higher than those for smear microscopy. The Xpert MTB/RIF assay on bronchoalveolar lavage fluid could serve as an additional rapid diagnostic tool for PTB in a high TB-burden country and improve the time to TB treatment initiation in patients with PTB. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Analysis of Triplet Exciton Loss Pathways in PTB7:PC71BM Bulk Heterojunction Solar Cells

NASA Astrophysics Data System (ADS)

Kraus, Hannes; Heiber, Michael C.; Väth, Stefan; Kern, Julia; Deibel, Carsten; Sperlich, Andreas; Dyakonov, Vladimir

2016-07-01

A strategy for increasing the conversion efficiency of organic photovoltaics has been to increase the VOC by tuning the energy levels of donor and acceptor components. However, this opens up a new loss pathway from an interfacial charge transfer state to a triplet exciton (TE) state called electron back transfer (EBT), which is detrimental to device performance. To test this hypothesis, we study triplet formation in the high performing PTB7:PC71BM blend system and determine the impact of the morphology-optimizing additive 1,8-diiodoctane (DIO). Using photoluminescence and spin-sensitive optically detected magnetic resonance (ODMR) measurements at low temperature, we find that TEs form on PC71BM via intersystem crossing from singlet excitons and on PTB7 via EBT mechanism. For DIO blends with smaller fullerene domains, an increased density of PTB7 TEs is observed. The EBT process is found to be significant only at very low temperature. At 300 K, no triplets are detected via ODMR, and electrically detected magnetic resonance on optimized solar cells indicates that TEs are only present on the fullerenes. We conclude that in PTB7:PC71BM devices, TE formation via EBT is impacted by fullerene domain size at low temperature, but at room temperature, EBT does not represent a dominant loss pathway.

Differences Between Pediatric Extra-Pulmonary and Pulmonary Tuberculosis: a Warning Sign for the Future

PubMed Central

Devrim, İlker; Aktürk, Hüseyin; Bayram, Nuri; Apa, Hurşit; Tulumoğlu, Şener; Devrim, Fatma; Erdem, Tülin; Gulfidan, Gamze; Ayhan, Yüce; Tamsel, İpek; Can, Demet; Alper, Hüdaver

2014-01-01

Background Tuberculosis (TB) remains a major global health problem. The childhood tuberculosis has some unique features different which makes the diagnosis more complicated. Here we described the epidemiologic, clinical and microbiologic features of children with extra pulmonary and pulmonary TB. Methods The data of the patients <14 years with active TB were collected and compared in pulmonary (PTB) and extrapulmonary TB (EXPTB) patients. Results A total of 128 cases was included. Forty-two cases occurred in children were < 5 years of age; 41 cases between 6–10 years and 45 cases > 10 years. PTB was present in 75,0% of the cases, and EXPTB was present in 25% of cases. There was no significant difference between the EXPTB and PTB by means of distribution of age groups (p=0,201). The rate of patients free of constitutional symptoms were significantly higher in EXPTB compared to PTB(p=0,000). There was no significant difference between EXPTB and PTB by means of sources detection(p=0,069). Conclusion TB is still a major public health problem. EXPTB has an insidious and silent onset without any constitutional symptoms, and both microbiological confirmation and the source by an adult are not frequently found. Moreover, detection of the adult source is mandatory for controlling the TB disease in children PMID:25237471

Effect of IFN-γ, IL-12 and IL-10 cytokine production and mRNA expression in tuberculosis patients with diabetes mellitus and their household contacts.

PubMed

Meenakshi, Ponnana; Ramya, Sivangala; Lavanya, Joshi; Vijayalakshmi, Valluri; Sumanlatha, Gaddam

2016-05-01

The study was carried out to understand the influence of IFN-γ, IL-12 and IL-10 cytokine production and expression in tuberculosis patients with diabetes mellitus (TBDM) and their household contacts (HHC). The study involved a total of 300 subjects, 50 in each category of TBDM, TBDM HHC, pulmonary tuberculosis patients (PTB), PTB HHC, DM and healthy controls (HC). TBDM, PTB and their HHC, 25 each were followed at different intervals to determine their immune responses in Ag85A stimulated culture supernatants by Enzyme Linked Immunosorbent Assay (ELISA). mRNA expression by TRIZOL method in 5 cases of each category and follow-up studies were performed. IFN-γ and IL-12 cytokine production markedly decreased and that of IL-10 increased after Ag85A M.tb stimulation, however anti TB treatment reconstituted the response in TBDM and PTB patients. The household contacts revealed cytokine gene expression similar to that of patients and two of them developed the disease during follow-up. Cytokine responses of the patients retained after treatment highlighting the antigen importance, hence further studies with recombinant cytokines may help in coming up with a biomarker. Analogous immune responses of household contacts with the TBDM and PTB patients may assist in recognizing the high risk individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interrelationship of cytokines, hypothalamic-pituitary-adrenal axis hormones, and psychosocial variables in the prediction of preterm birth.

PubMed

Pearce, B D; Grove, J; Bonney, E A; Bliwise, N; Dudley, D J; Schendel, D E; Thorsen, P

2010-01-01

To examine the relationship of biological mediators (cytokines, stress hormones), psychosocial, obstetric history, and demographic factors in the early prediction of preterm birth (PTB) using a comprehensive logistic regression model incorporating diverse risk factors. In this prospective case-control study, maternal serum biomarkers were quantified at 9-23 weeks' gestation in 60 women delivering at <37 weeks compared to 123 women delivering at term. Biomarker data were combined with maternal sociodemographic factors and stress data into regression models encompassing 22 preterm risk factors and 1st-order interactions. Among individual biomarkers, we found that macrophage migration inhibitory factor (MIF), interleukin-10, C-reactive protein (CRP), and tumor necrosis factor-alpha were statistically significant predictors of PTB at all cutoff levels tested (75th, 85th, and 90th percentiles). We fit multifactor models for PTB prediction at each biomarker cutoff. Our best models revealed that MIF, CRP, risk-taking behavior, and low educational attainment were consistent predictors of PTB at all biomarker cutoffs. The 75th percentile cutoff yielded the best predicting model with an area under the ROC curve of 0.808 (95% CI 0.743-0.874). Our comprehensive models highlight the prominence of behavioral risk factors for PTB and point to MIF as a possible psychobiological mediator. Copyright (c) 2010 S. Karger AG, Basel.

Antibiotics for treating bacterial vaginosis in pregnancy

PubMed Central

McDonald, Helen Margaret; Brocklehurst, Peter; Gordon, Adrienne

2014-01-01

Background Bacterial vaginosis is an imbalance of the normal vaginal flora with an overgrowth of anaerobic bacteria and a lack of the normal lactobacillary flora. Bacterial vaginosis during pregnancy has been associated with poor perinatal outcome and, in particular, preterm birth (PTB). Identification and treatment may reduce the risk of PTB and its consequences. Objectives To assess the effects of antibiotic treatment of bacterial vaginosis in pregnancy. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (May 2006). We updated this search on 18 November 2010 and added the results to the awaiting classification section. Selection criteria Randomized trials comparing antibiotic treatment with placebo or no treatment, or comparing two or more antibiotic regimens in pregnant women with bacterial vaginosis or intermediate vaginal flora. Data collection and analysis Two review authors assessed trials and extracted data independently. We contacted study authors for additional information. Main results We included fifteen trials of good quality, involving 5888 women. Antibiotic therapy was effective at eradicating bacterial vaginosis during pregnancy (Peto odds ratio (OR) 0.17, 95% confidence interval (CI) 0.15 to 0.20; 10 trials, 4357 women). Treatment did not reduce the risk of PTB before 37 weeks (Peto OR 0.91, 95% CI 0.78 to 1.06; 15 trials, 5888 women), or the risk of preterm prelabour rupture of membranes (PPROM) (Peto OR 0.88, 95% CI 0.61 to 1.28; four trials, 2579 women). However, treatment before 20 weeks’ gestation may reduce the risk of preterm birth less than 37 weeks (Peto OR 0.72, 95% CI 0.55 to 0.95; five trials, 2387 women). In women with a previous PTB, treatment did not affect the risk of subsequent PTB (Peto OR 0.83, 95% CI 0.59 to 1.17, five trials of 622); however, it may decrease the risk of PPROM (Peto OR 0.14, 95% CI 0.05 to 0.38) and low birthweight (Peto OR 0.31, 95% CI 0.13 to 0.75)(two trials, 114 women). In women with abnormal vaginal flora (intermediate flora or bacterial vaginosis) treatment may reduce the risk of PTB before 37 weeks (Peto OR 0.51, 95% CI 0.32 to 0.81; two trials, 894 women). Clindamycin did not reduce the risk of PTB before 37 weeks (Peto OR 0.80, 95% CI 0.60 to 1.05; six trials, 2406 women). Authors’ conclusions Antibiotic treatment can eradicate bacterial vaginosis in pregnancy. This review provides little evidence that screening and treating all pregnant women with asymptomatic bacterial vaginosis will prevent PTB and its consequences. However, there is some suggestion that treatment before 20 weeks’ gestation may reduce the risk of PTB. This needs to be further verified by future trials. [Note: The eleven citations in the awaiting assessment section of the review may alter the conclusions of the review once assessed.] PMID:17253447

EXPOSURE TO AREA-LEVEL PRETERM BIRTH DISPARITY AND EFFECTS ON BIRTH OUTCOMES

EPA Science Inventory

Black–white disparity in preterm birth (PTB) is persistent and not explained by individual factors. Given that exposure to inequality is associated with increased risk of adverse health, we examined PTB risk (birth <37 weeks gestational age) explained by living in U.S. census tra...

Species of fine particulate matter and the risk of preterm birth

EPA Science Inventory

Particulate matter (PM) has been variably associated with preterm birth (PTB), but the roles of PM species have been less studied. We estimated risk of birth in 4 preterm categories (risks reported as PTBs per 106 pregnancies; PTB categories = gestational age of 20-27; 28-31; 32-...

Long noncoding RNA H19 interacts with polypyrimidine tract-binding protein 1 to reprogram hepatic lipid homeostasis.

PubMed

Liu, Chune; Yang, Zhihong; Wu, Jianguo; Zhang, Li; Lee, Sangmin; Shin, Dong-Ju; Tran, Melanie; Wang, Li

2018-05-01

H19 is an imprinted long noncoding RNA abundantly expressed in embryonic liver and repressed after birth. We show that H19 serves as a lipid sensor by synergizing with the RNA-binding polypyrimidine tract-binding protein 1 (PTBP1) to modulate hepatic metabolic homeostasis. H19 RNA interacts with PTBP1 to facilitate its association with sterol regulatory element-binding protein 1c mRNA and protein, leading to increased stability and nuclear transcriptional activity. H19 and PTBP1 are up-regulated by fatty acids in hepatocytes and in diet-induced fatty liver, which further augments lipid accumulation. Ectopic expression of H19 induces steatosis and pushes the liver into a "pseudo-fed" state in response to fasting by promoting sterol regulatory element-binding protein 1c protein cleavage and nuclear translocation. Deletion of H19 or knockdown of PTBP1 abolishes high-fat and high-sucrose diet-induced steatosis. Our study unveils an H19/PTBP1/sterol regulatory element-binding protein 1 feedforward amplifying signaling pathway to exacerbate the development of fatty liver. (Hepatology 2018;67:1768-1783). © 2017 by the American Association for the Study of Liver Diseases.

RNA-Binding Proteins in Female Reproductive Pathologies.

PubMed

Khalaj, Kasra; Miller, Jessica E; Fenn, Christian R; Ahn, SooHyun; Luna, Rayana L; Symons, Lindsey; Monsanto, Stephany P; Koti, Madhuri; Tayade, Chandrakant

2017-06-01

RNA-binding proteins are key regulatory molecules involved primarily in post-transcriptional gene regulation of RNAs. Post-transcriptional gene regulation is critical for adequate cellular growth and survival. Recent reports have shown key interactions between these RNA-binding proteins and other regulatory elements, such as miRNAs and long noncoding RNAs, either enhancing or diminishing their response to RNA stabilization. Many RNA-binding proteins have been reported to play a functional role in mediation of cytokines involved in inflammation and immune dysfunction, and some have been classified as global post-transcriptional regulators of inflammation. The ubiquitous expression of RNA-binding proteins in a wide variety of cell types and their unique mechanisms of degradative action provide evidence that they are involved in reproductive tract pathologies. Aberrant inflammation and immune dysfunction are major contributors to the pathogenesis and disease pathophysiology of many reproductive pathologies, including ovarian and endometrial cancers in the female reproductive tract. Herein, we discuss various RNA-binding proteins and their unique contributions to female reproductive pathologies with a focus on those mediated by aberrant inflammation and immune dysfunction. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Performance and Applications of an Ensemble of Atomic Fountains

DTIC Science & Technology

2012-01-01

continuous operation. At some institutions, only one fountain clock contributes to the ensemble at a given time, although two clocks at PTB and three at...at USNO is funded by SPAWAR. REFERENCES [1] A. Bauch, S. Weyers, D. Piester, E. Staliuniene, and W. Yang, “Generation of UTC( PTB ) as a fountain

The Relations between Teasing and Bullying and Middle School Standardized Exam Performance

ERIC Educational Resources Information Center

Lacey, Anna; Cornell, Dewey; Konold, Timothy

2017-01-01

This study examined the relations between the schoolwide prevalence of teasing and bullying (PTB) and schoolwide academic performance in a sample of 271 Virginia middle schools. In addition, the study examined the mediating effects of student engagement. A three-step sequence of path models investigated associations between schoolwide PTB and…

Evaluation of Gas-filled Ionization Chamber Method for Radon Measurement at Two Reference Facilities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishikawa, Tetsuo; Tokonami, Shinji; Kobayashi, Yosuke

2008-08-07

For quality assurance, gas-filled ionization chamber method was tested at two reference facilities for radon calibration: EML (USA) and PTB (Germany). Consequently, the radon concentrations estimated by the ionization chamber method were in good agreement with the reference radon concentrations provided by EML as well as PTB.

KEY COMPARISON: Final report of EUROMET Project 696: pH determination of a phthalate buffer

NASA Astrophysics Data System (ADS)

Spitzer, Petra; Charlet, Philippe; Eberhard, Ralf; Karpov, Oleg V.; Philippe, Rachel; Rivier, Cedric; Maximov, Igor; Sudmeier, Uwe

2005-01-01

The EUROMET project 696, a trilateral comparison between PTB, Germany, LNE, France and VNIIFTRI, Russia was performed in order to demonstrate and document the capability of the participants to measure the pH of a phthalate buffer by the primary measurement procedure for pH. Good agreement of the reported results was observed. The sample was very similar to the one used in the comparison CCQM-K17. PTB acts as pilot laboratory in CCQM-K17 and in EUROMET 696. This comparison allows one to link the results obtained by LNE to the CCQM-K17 key comparison through the degree of equivalence of PTB. On the other hand, the discrepancy between measured pH values at the VNIIFTRI and PTB for the same type of buffer solution decreased, as compared with a bilateral comparison in 1997. Main text. To reach the main text of this paper, click on Final Report. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the Mutual Recognition Arrangement (MRA).

Toward Efficient Thick Active PTB7 Photovoltaic Layers Using Diphenyl Ether as a Solvent Additive.

PubMed

Zheng, Yifan; Goh, Tenghooi; Fan, Pu; Shi, Wei; Yu, Junsheng; Taylor, André D

2016-06-22

The development of thick organic photovoltaics (OPV) could increase absorption in the active layer and ease manufacturing constraints in large-scale solar panel production. However, the efficiencies of most low-bandgap OPVs decrease substantially when the active layers exceed ∼100 nm in thickness (because of low crystallinity and a short exciton diffusion length). Herein, we report the use of solvent additive diphenyl ether (DPE) that facilitates the fabrication of thick (180 nm) active layers and triples the power conversion efficiency (PCE) of conventional thienothiophene-co-benzodithiophene polymer (PTB7)-based OPVs from 1.75 to 6.19%. These results demonstrate a PCE 20% higher than those of conventional (PTB7)-based OPV devices using 1,8-diiodooctane. Morphology studies reveal that DPE promotes the formation of nanofibrillar networks and ordered packing of PTB7 in the active layer that facilitate charge transport over longer distances. We further demonstrate that DPE improves the fill factor and photocurrent collection by enhancing the overall optical absorption, reducing the series resistance, and suppressing bimolecular recombination.

Hierarchical Nanomorphologies Promote Exciton Dissociation in Polymer: Fullerene Bulk Heterojunction Solar Cells

NASA Astrophysics Data System (ADS)

Chen, Wei; Darling, Seth

2012-02-01

In the last fifteen years, research efforts have led to organic photovoltaic (OPV) devices with power conversion efficiencies (PCEs) up to ˜8%, but these values are still insufficient for the devices to become widely marketable. To further improve solar cell performance a thorough understanding of the complex structure-property relationships in the OPV devices is required. In this work, we demonstrated that the OPV active layer of PTB7:fullerene bulk heterojunction (BHJ) solar cells, which set a historic record of PCE (7.4%), involves hierarchical nanomorphologies ranging from several nanometers of crystallites to tens of nanometers of nanocrystallite aggregates in PTB7-rich and fullerene-rich domains, themselves hundreds of nanometers in size. These hierarchical nanomorphologies with optimum crystallinity and intermixing of PTB7 with fullerenes are coupled to significantly enhanced exciton dissociation, which consequently contribute to photocurrent, leading to the superior performance of PTB7:fullerene BHJ solar cells. New insights of performance-related structures afforded by the current study should aid in the rational design of even higher performance polymeric solar cells.

Ab initio modeling of excitonic and charge-transfer states in organic semiconductors: the PTB1/PCBM low band gap system.

PubMed

Borges, Itamar; Aquino, Adélia J A; Köhn, Andreas; Nieman, Reed; Hase, William L; Chen, Lin X; Lischka, Hans

2013-12-11

A detailed quantum chemical simulation of the excitonic and charge-transfer (CT) states of a bulk heterojunction model containing poly(thieno[3,4-b]thiophene benzodithiophene) (PTB1)/[6,6]-phenyl-C61-butyric acid methyl ester (PCBM) is reported. The largest molecular model contains two stacked PTB1 trimer chains interacting with C60 positioned on top of and lateral to the (PTB1)3 stack. The calculations were performed using the algebraic diagrammatic construction method to second order (ADC(2)). One main result of the calculations is that the CT states are located below the bright inter-chain excitonic state, directly accessible via internal conversion processes. The other important aspects of the calculations are the formation of discrete bands of CT states originating from the lateral C60's and the importance of inter-chain charge delocalization for the stability of the CT states. A simple model for the charge separation step is also given, revealing the energetic feasibility of the overall photovoltaic process.

Activation of macrophages and interference with CD4+ T-cell stimulation by Mycobacterium avium subspecies paratuberculosis and Mycobacterium avium subspecies avium

PubMed Central

Lage, Susanne Zur; Goethe, Ralph; Darji, Ayub; Valentin-Weigand, Peter; Weiss, Siegfried

2003-01-01

Mycobacterium avium subspecies paratuberculosis (M. ptb) and M. avium subspecies avium (M. avium) are closely related but exhibit significant differences in their interaction with the host immune system. The macrophage line, J774, was infected with M. ptb and M. avium and analysed for cytokine production and stimulatory capacity towards antigen-specific CD4+ T cells. Under all conditions J774 cells were activated to produce proinflammatory cytokines. No influence on the expression of major histocompatibility complex (MHC) class II, intracellular adhesion molecule-1 (ICAM-1), B7.1, B7.2 or CD40 was found. However, the antigen-specific stimulatory capacity of J774 cells for a CD4+ T-cell line was significantly inhibited after infection with M. ptb, but not with M. avium. When a T-cell hybridoma expressing a T-cell receptor identical to that of the T-cell line was used, this inhibition was not observed, suggesting that costimulation which is essential for the CD4+ T-cell line is influenced by the pathogenic bacterium M. ptb. PMID:12519304

Maternal socioeconomic factors and adverse perinatal outcomes in two birth cohorts, 1997/98 and 2010, in São Luís, Brazil.

PubMed

Cavalcante, Nádia Carenina Nunes; Simões, Vanda Maria Ferreira; Ribeiro, Marizélia Rodrigues Costa; Lamy-Filho, Fernando; Barbieri, Marco Antonio; Bettiol, Heloisa; Silva, Antônio Augusto Moura da

2017-01-01

Several studies have identified social inequalities in low birth weight (LBW), preterm birth (PTB), and intrauterine growth restriction (IUGR), which, in recent years, have diminished or disappeared in certain locations. Estimate the LBW, PTB, and IUGR rates in São Luís, Maranhão, Brazil, in 2010, and check for associations between socioeconomic factors and these indicators. This study is based on a birth cohort performed in São Luís. It included 5,051 singleton hospital births in 2010. The chi-square test was used for proportion comparisons, while simple and multiple Poisson regression models with robust error variance were used to estimate relative risks. LBW, PTB and IUGR rates were 7.5, 12.2, and 10.3% respectively. LBW was higher in low-income families, while PTB and IUGR were not associated with socioeconomic factors. The absence or weak association of these indicators with social inequality point to improvements in health care and/or in social conditions in São Luís.

Phosphorylated c-MPL tyrosine 591 regulates thrombopoietin-induced signaling

PubMed Central

Sangkhae, Veena; Saur, Sebastian Jonas; Kaushansky, Alexis; Kaushansky, Kenneth; Hitchcock, Ian Stuart

2018-01-01

Thrombopoietin (TPO) is the primary regulator of platelet production, affecting cell survival, proliferation and differentiation through binding to and stimulation of the cell surface receptor c-MPL. Activating mutations in c-MPL constitutively stimulate downstream signaling pathways, leading to aberrant hematopoiesis and contribute to development of myeloproliferative neoplasms. Several studies have mapped the tyrosine residues within the cytoplasmic domain of c-MPL that mediate these cellular signals; however, secondary signaling pathways are incompletely understood. In this study we focused on c-MPL tyrosine 591 (Y591). We found Y591 of wild-type c-MPL to be phosphorylated in the presence of TPO. Additionally, eliminating Y591 phosphorylation by mutation to Phe resulted in decreased total receptor phosphorylation. Using an SH2/PTB domain binding microarray, we identified novel c-MPL binding partners for phosphorylated Y591, including Src homology phosphatase-1 (SHP-1), spleen tyrosine kinase (SYK) and Bruton's tyrosine kinase (BTK). The functional significance of binding partners was determined through siRNA treatment of Ba/F3-MPL cells, confirming that the increase in pERK1/2 resulting from removal of Y591 may be mediated by SYK. These findings identify a novel negative regulatory pathway that controls TPO-mediated signaling, advancing our understanding of the mechanisms required for successful maintenance of hematopoietic stem cells and megakaryocyte development. PMID:24607955

Catalogue of tooth brush head designs.

PubMed

Voelker, Marsha A; Bayne, Stephen C; Liu, Ying; Walker, Mary P

2013-06-01

Manual toothbrushes (MTBs) and power toothbrushes (PTBs) are effective oral physiotherapy aids for plaque removal. End-rounded bristles are safer and reduce damage to oral tissues. Nylon bristles are more effective in plaque removal because the bristle is stiffer than natural bristles. In the last 10 years the number of options for MTBs and PTBs has expanded significantly and there is very little information providing a reference frame for the design characteristics of the heads. The present in vitro study characterized a variety of MTB and PTB heads to provide a reference library for other research comparisons which might be made. Various commercial MTB and PTB heads were used to characterize the following: bristle size, shape, diameter, number of tufts, number of bristles per tuft and surface characteristics. Photographs were collected from the side, at 45 degrees and the top of each toothbrush (TB) head using a scanning electron microscope and digital camera. Images were analyzed (Soft Imaging System) for bristle features and designs. One-way ANOVA (p ≤ 0.05) was performed to detect differences among TB types within MTB and PTB groups and between pooled values for MTB and PTB groups. There were significant differences (p ≤ 0.05) in toothbrush bristle diameter and bristle shape. In contrast, there were no significant differences between PTB vs. MTB in regards to bristle diameter, bristle count and tuft count. The results suggest that although there are wide variations in toothbrush head designs, significant differences were found only in relation to bristle diameter and shape.

Density functional theory investigation of opto-electronic properties of thieno[3,4-b]thiophene and benzodithiophene polymer and derivatives and their applications in solar cell

NASA Astrophysics Data System (ADS)

Khoshkholgh, Mehri Javan; Marsusi, Farah; Abolhassani, Mohammad Reza

2015-02-01

PTBs polymers with thieno[3,4-b]thiophene [TT] and benzodithiophene [BDT] units have particular properties, which demonstrate it as one of the best group of donor materials in organic solar cells. In the present work, density functional theory (DFT) is applied to investigate the optimized structure, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), band gap and dihedral angle of PTB7 at B3LYP/6-31G(d). Two different approaches are applied to carry out these investigations: Oligomer extrapolation technique and periodic boundary condition (PBC) method. The results obtained from PBC-DFT method are in fair agreement with experiments. Based on these reliable outcomes; the investigations continued to perform some derivatives of PTB7. In this study, sulfur is substituted by nitrogen, oxygen, silicon, phosphor or selenium atoms in pristine PTB7. Due to the shift of HOMO and LUMO levels, smaller band gaps are predicted to appear in some derivatives in comparison with PTB7. Maximum theoretical efficiencies, η, of the mentioned derivatives as well as local difference of dipole moments between the ground and excited states (Δμge) are computed. The results indicate that substitution of sulfur by nitrogen or oxygen in BDT unit, and silicon or phosphor in TT unit of pristine PTB7 leads to a higher η as well as Δμge.

Rapid diagnosis of pulmonary tuberculosis and detection of drug resistance by combined simultaneous amplification testing and reverse dot blot.

PubMed

Chen, Yiwen; Zhang, Lahong; Hong, Liquan; Luo, Xian; Chen, Juping; Tang, Leiming; Chen, Jiahuan; Liu, Xia; Chen, Zhaojun

2018-06-01

Making a correct and rapid diagnosis is essential for managing pulmonary tuberculosis (PTB), particularly multidrug-resistant tuberculosis. We aimed to evaluate the efficacy of the combination of simultaneous amplification testing (SAT) and reverse dot blot (RDB) for the rapid detection of Mycobacterium tuberculosis (MTB) and drug-resistant mutants in respiratory samples. 225 suspected PTB and 32 non-TB pulmonary disease samples were collected. All sputum samples were sent for acid-fast bacilli smear, SAT, culture and drug susceptibility testing (DST) by the BACTEC TM MGIT TM 960 system. 53 PTB samples were tested by both RDB and DNA sequencing to identify drug resistance genes and mutated sites. The SAT positive rate (64.9%) was higher than the culture positive rate (55.1%), with a coincidence rate of 83.7%. The sensitivity and specificity of SAT for diagnosing PTB were 66.7% and 100%, respectively, while those for culture were 53.9% and 84.2%, respectively. RDB has high sensitivity and specificity in identifying drug resistance genes and mutated sites. The results of RDB correlated well with those of DST and DNA sequencing, with coincidence rates of 92.5% and 98.1%, respectively. The combination of SAT and RDB is promising for rapidly detecting PTB and monitoring drug resistance in clinical laboratories. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pre-immigration screening process and pulmonary tuberculosis among Ethiopian migrants in Israel.

PubMed

Mor, Z; Lerman, Y; Leventhal, A

2008-08-01

More than 75,000 displaced Ethiopians have moved to Israel. Tuberculosis (TB) incidence in Ethiopia is 44 times higher than in Israel (344 versus 8 cases per 100,000 inhabitants, respectively). The aims of the present retrospective cohort study were to evaluate the pre-immigration screening process initiated in 2001 on pulmonary TB (PTB) morbidity and to assess its cost-effectiveness. Ethiopian immigrants who were screened before departure (study group) were compared with those who were screened after arrival (comparison group). Between 1998 and 2005, 24,051 Ethiopian immigrants arrived in Israel. PTB was diagnosed in 332 (1.4%) immigrants, an incidence density of 325 patients per 100,000 person-yrs. PTB cumulative incidence was lower in the study group than in the comparison group: 711 compared with 1,746 patients per 100,000 immigrants, respectively (rate ratio 0.4). PTB was detected significantly earlier in the study group than in the comparison group: 193 versus 487 days after entry, respectively. Disease incidence declined significantly during the first 2 yrs following immigration. A 5-yr predictive model indicated that 98 individuals would be free of PTB, saving US$91,055 on annual treatment cost, due to screening. The pre-immigration screening process reduced pulmonary tuberculosis incidence in subsequent years following immigration. Pulmonary tuberculosis was diagnosed earlier in the screened group than in the comparison group and the process was found to be both cost-beneficial and cost-effective.

CD3+ICOS+ T cells show differences in the synthesis of nitric oxide, IFN-γ, and IL-10 in patients with pulmonary tuberculosis or in healthy household contacts.

PubMed

Lara-Rodríguez, Carmen; Alvarado-Vásquez, Noé; Bernal, Demetrio; Gorocica, Patricia; Zenteno, Edgar; Lascuraín, Ricardo

2016-11-01

Evidence indicates that more than 90 % of infected individuals never develop active tuberculosis. This fact highlights the relevance of the immune response in tuberculosis control. The inducible co-stimulator (ICOS) is a regulator of the function, differentiation, proliferation, and activation of T cells. Moreover, T cells synthesise nitric oxide (NO), interferon gamma (IFN-γ), and interleukin (IL)-10, which help regulate the immune response to tuberculosis. Therefore, we assessed the synthesis of NO, IFN-γ, and IL-10 in CD3 + ICOS + T cells from healthy individuals, household contacts (HHC), and patients with active pulmonary tuberculosis (PTB), previously stimulated with the antigen H37Rv. Our results indicated a significant increase in both the percentage of ICOS + cells and CD3 + ICOS + T cells producing NO, IFN-γ, and IL-10 in cells obtained from patients with PTB (p < 0.01). In addition, a high mitochondrial membrane potential (ΔΨ m ) in CD3 + ICOS + T cells was observed in the cells from HHC and from PTB patients, and is associated with the activation of T cells. In conclusion, results show that the CD3 + ICOS + T cells obtained from PTB patients are the main producers of NO, IFN-γ, and IL-10. In addition, our results imply that NO is a modulator of ICOS expression of T cells from PTB patients.

Perinatal outcomes for Asian, Native Hawaiian, and other Pacific Islander mothers of single and multiple race/ethnicity: California and Hawaii, 2003-2005.

PubMed

Schempf, Ashley H; Mendola, Pauline; Hamilton, Brady E; Hayes, Donald K; Makuc, Diane M

2010-05-01

We examined characteristics and birth outcomes of Asian/Pacific Islander (API) mothers to determine whether differences in outcomes existed between mothers of single race/ethnicity and multiple race/ethnicity. We used data from California and Hawaii birth certificates from 2003 through 2005 to describe variation in birth outcomes for API subgroups by self-reported maternal race/ethnicity (single versus multiple race or API subgroup), and we also compared these outcomes to those of non-Hispanic White women. Low birthweight (LBW) and preterm birth (PTB) varied more among API subgroups than between mothers of single versus multiple race/ethnicity. After adjustment for sociodemographic and behavioral risk factors, API mothers of multiple race/ethnicity had outcomes similar to mothers of single race/ethnicity, with exceptions for multiple-race/ethnicity Chinese (higher PTB), Filipino (lower LBW and PTB), and Thai (higher LBW) subgroups. Compared with single-race non-Hispanic Whites, adverse outcomes were elevated for most API subgroups: only single-race/ethnicity Korean mothers had lower rates of both LBW (3.4%) and PTB (5.6%); single-race/ethnicity Cambodian, Laotian, and Marshallese mothers had the highest rates of both LBW (8.8%, 9.2%, and 8.4%, respectively) and PTB (14.0%, 13.7%, and 18.8%, respectively). Strategies to improve birth outcomes for API mothers should consider variations in risk by API subgroup and multiple race/ethnicity.

Density functional theory investigation of opto-electronic properties of thieno[3,4-b]thiophene and benzodithiophene polymer and derivatives and their applications in solar cell.

PubMed

Khoshkholgh, Mehri Javan; Marsusi, Farah; Abolhassani, Mohammad Reza

2015-02-05

PTBs polymers with thieno[3,4-b]thiophene [TT] and benzodithiophene [BDT] units have particular properties, which demonstrate it as one of the best group of donor materials in organic solar cells. In the present work, density functional theory (DFT) is applied to investigate the optimized structure, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), band gap and dihedral angle of PTB7 at B3LYP/6-31G(d). Two different approaches are applied to carry out these investigations: Oligomer extrapolation technique and periodic boundary condition (PBC) method. The results obtained from PBC-DFT method are in fair agreement with experiments. Based on these reliable outcomes; the investigations continued to perform some derivatives of PTB7. In this study, sulfur is substituted by nitrogen, oxygen, silicon, phosphor or selenium atoms in pristine PTB7. Due to the shift of HOMO and LUMO levels, smaller band gaps are predicted to appear in some derivatives in comparison with PTB7. Maximum theoretical efficiencies, η, of the mentioned derivatives as well as local difference of dipole moments between the ground and excited states (Δμge) are computed. The results indicate that substitution of sulfur by nitrogen or oxygen in BDT unit, and silicon or phosphor in TT unit of pristine PTB7 leads to a higher η as well as Δμge. Copyright © 2014 Elsevier B.V. All rights reserved.

Highly Efficient Ternary-Blend Polymer Solar Cells Enabled by a Nonfullerene Acceptor and Two Polymer Donors with a Broad Composition Tolerance.

PubMed

Xu, Xiaopeng; Bi, Zhaozhao; Ma, Wei; Wang, Zishuai; Choy, Wallace C H; Wu, Wenlin; Zhang, Guangjun; Li, Ying; Peng, Qiang

2017-12-01

In this work, highly efficient ternary-blend organic solar cells (TB-OSCs) are reported based on a low-bandgap copolymer of PTB7-Th, a medium-bandgap copolymer of PBDB-T, and a wide-bandgap small molecule of SFBRCN. The ternary-blend layer exhibits a good complementary absorption in the range of 300-800 nm, in which PTB7-Th and PBDB-T have excellent miscibility with each other and a desirable phase separation with SFBRCN. In such devices, there exist multiple energy transfer pathways from PBDB-T to PTB7-Th, and from SFBRCN to the above two polymer donors. The hole-back transfer from PTB7-Th to PBDB-T and multiple electron transfers between the acceptor and the donor materials are also observed for elevating the whole device performance. After systematically optimizing the weight ratio of PBDB-T:PTB7-Th:SFBRCN, a champion power conversion efficiency (PCE) of 12.27% is finally achieved with an open-circuit voltage (V oc ) of 0.93 V, a short-circuit current density (J sc ) of 17.86 mA cm -2 , and a fill factor of 73.9%, which is the highest value for the ternary OSCs reported so far. Importantly, the TB-OSCs exhibit a broad composition tolerance with a high PCE over 10% throughout the whole blend ratios. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antenatal interventions to reduce preterm birth: an overview of Cochrane systematic reviews

PubMed Central

2014-01-01

Background Several factors are associated with an increased risk of preterm birth (PTB); therefore, various interventions might have the potential to influence it. Due to the large number of interventions that address PTB, the objective of this overview is to summarise evidence from Cochrane reviews regarding the effects and safety of these different interventions. Methods We conducted a systematic literature search in the Cochrane Database of Systematic Reviews. Included reviews should be based on randomised controlled trials comparing antenatal non-pharmacological and pharmacological interventions that directly or indirectly address PTB with placebo/no treatment or routine care in pregnant women at less than 37 completed weeks of gestation without signs of threatened preterm labour. We considered PTB at less than 37 completed weeks of gestation as the primary outcome. Results We included 56 Cochrane systematic reviews. Three interventions increased PTB risk significantly. Twelve interventions led to a statistically significant lower incidence of PTBs. However, this reduction was mostly observed in defined at-risk subgroups of pregnant women. The remaining antenatal interventions failed to prove a significant effect on PTB < 37 weeks, but some of them at least showed a positive effect in secondary outcomes (e.g., reduction in early PTBs). As an unintended result of this review, we identified 28 additional Cochrane reviews which intended to report on PTB < 37 weeks, but were not able to find any RCTs reporting appropriate data. Conclusions The possible effects of a diverse range of interventions on PTB have been evaluated in Cochrane systematic reviews. Few interventions have been demonstrated to be effective and a small number have been found to be harmful. For around half of the interventions evaluated, the Cochrane review concluded that there was insufficient evidence to provide sound recommendations for clinical practice. No RCT evidence is available for a number of potentially relevant interventions. PMID:24758148

Antenatal interventions to reduce preterm birth: an overview of Cochrane Systematic Reviews.

PubMed

Piso, Brigitte; Zechmeister-Koss, Ingrid; Winkler, Roman

2014-04-23

Several factors are associated with an increased risk of preterm birth (PTB); therefore, various interventions might have the potential to influence it. Due to the large number of interventions that address PTB, the objective of this overview is to summarise evidence from Cochrane reviews regarding the effects and safety of these different interventions. We conducted a systematic literature search in the Cochrane Database of Systematic Reviews. Included reviews should be based on randomised controlled trials comparing antenatal non-pharmacological and pharmacological interventions that directly or indirectly address PTB with placebo/no treatment or routine care in pregnant women at less than 37 completed weeks of gestation without signs of threatened preterm labour. We considered PTB at less than 37 completed weeks of gestation as the primary outcome. We included 56 Cochrane systematic reviews. Three interventions increased PTB risk significantly. Twelve interventions led to a statistically significant lower incidence of PTBs. However, this reduction was mostly observed in defined at-risk subgroups of pregnant women. The remaining antenatal interventions failed to prove a significant effect on PTB < 37 weeks, but some of them at least showed a positive effect in secondary outcomes (e.g., reduction in early PTBs). As an unintended result of this review, we identified 28 additional Cochrane reviews which intended to report on PTB < 37 weeks, but were not able to find any RCTs reporting appropriate data. The possible effects of a diverse range of interventions on PTB have been evaluated in Cochrane systematic reviews. Few interventions have been demonstrated to be effective and a small number have been found to be harmful. For around half of the interventions evaluated, the Cochrane review concluded that there was insufficient evidence to provide sound recommendations for clinical practice. No RCT evidence is available for a number of potentially relevant interventions.

IL-10 -1082 A>G (rs1800896) polymorphism confers susceptibility to pulmonary tuberculosis in Caucasians but not in Asians and Africans: a meta-analysis.

PubMed

Areeshi, Mohammed Y; Mandal, Raju K; Dar, Sajad A; Jawed, Arshad; Wahid, Mohd; Lohani, Mohtashim; Panda, Aditya K; Mishra, Bhartendu N; Akhter, Naseem; Haque, Shafiul

2017-10-31

Earlier studies have shown that interlukin-10 ( IL-10 ) -1082 A>G gene polymorphism is implicated in susceptibility to pulmonary tuberculosis (PTB), but their results are inconsistent and inconclusive. In the present study, a meta-analysis was performed to analyze the potential association between IL-10 -1082 A>G gene polymorphism and PTB susceptibility. A quantitative synthesis was done using PubMed (Medline), EMBASE, and Google Scholar web databases search and meta-analysis was performed by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for all the genetic models. A total of 22 eligible studies comprising 4956 PTB cases and 6428 healthy controls were included in the analysis. We did not observe any increased or decreased risk of PTB in allelic contrast (G vs. A: P =0.985; OR = 1.001, 95% CI = 0.863-1.162), homozygous (GG vs. AA: P =0.889; OR = 1.029, 95% CI = 0.692-1.529), heterozygous (GA vs. AA: P =0.244; OR = 0.906, 95% CI = 0.767-1.070), dominant (GG + AG vs. AA: P =0.357; OR = 1.196, 95% CI = 0.817-1.752), and recessive (GG vs. AA + AG: P =0.364; OR = 0.921, 95% CI = 0.771-1.100) genetic models. Likewise, no association of IL-10 -1082 A>G polymorphism with PTB risk was observed in Asian and African population for all the genetic models. Interestingly, the dominant model (GG + AG vs. AA: P =0.004; OR = 1.694, 95% CI = 1.183-2.425) demonstrated increased risk of PTB in Caucasian population. This meta-analysis concludes that IL-10 -1082 A>G gene polymorphism is not significantly associated with overall, Asian and African population. However, this polymorphism is associated with Caucasian population. © 2017 The Author(s).

IL-10 -1082 A>G (rs1800896) polymorphism confers susceptibility to pulmonary tuberculosis in Caucasians but not in Asians and Africans: a meta-analysis

PubMed Central

Areeshi, Mohammed Y.; Mandal, Raju K.; Dar, Sajad A.; Jawed, Arshad; Wahid, Mohd; Lohani, Mohtashim; Panda, Aditya K.; Mishra, Bhartendu N.; Akhter, Naseem

2017-01-01

Background: Earlier studies have shown that interlukin-10 (IL-10) -1082 A>G gene polymorphism is implicated in susceptibility to pulmonary tuberculosis (PTB), but their results are inconsistent and inconclusive. In the present study, a meta-analysis was performed to analyze the potential association between IL-10 -1082 A>G gene polymorphism and PTB susceptibility. Methods: A quantitative synthesis was done using PubMed (Medline), EMBASE, and Google Scholar web databases search and meta-analysis was performed by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for all the genetic models. Results: A total of 22 eligible studies comprising 4956 PTB cases and 6428 healthy controls were included in the analysis. We did not observe any increased or decreased risk of PTB in allelic contrast (G vs. A: P=0.985; OR = 1.001, 95% CI = 0.863–1.162), homozygous (GG vs. AA: P=0.889; OR = 1.029, 95% CI = 0.692–1.529), heterozygous (GA vs. AA: P=0.244; OR = 0.906, 95% CI = 0.767–1.070), dominant (GG + AG vs. AA: P=0.357; OR = 1.196, 95% CI = 0.817–1.752), and recessive (GG vs. AA + AG: P=0.364; OR = 0.921, 95% CI = 0.771–1.100) genetic models. Likewise, no association of IL-10 -1082 A>G polymorphism with PTB risk was observed in Asian and African population for all the genetic models. Interestingly, the dominant model (GG + AG vs. AA: P=0.004; OR = 1.694, 95% CI = 1.183–2.425) demonstrated increased risk of PTB in Caucasian population. Conclusions: This meta-analysis concludes that IL-10 -1082 A>G gene polymorphism is not significantly associated with overall, Asian and African population. However, this polymorphism is associated with Caucasian population. PMID:28951522

Association between prenatal exposure to traffic-related air pollution and preterm birth in the PELAGIE mother-child cohort, Brittany, France. Does the urban-rural context matter?

PubMed

Bertin, Mélanie; Chevrier, Cécile; Serrano, Tania; Monfort, Christine; Rouget, Florence; Cordier, Sylvaine; Viel, Jean-François

2015-10-01

Evidence has accumulated that exposure to ambient air pollution during pregnancy may influence preterm birth (PTB) in urban settings. Conversely, this relation has barely been investigated in rural areas where individual characteristics (demographic, socioeconomic, and psychosocial factors) and environmental co-exposures may differ. We examined the association between prenatal exposure to traffic-related air pollution and PTB among pregnant women from the PELAGIE mother-child cohort (Brittany, France, 2002-2006) living in urban (n=1550) and rural (n=959) settings. Women's residences were classified as either urban or rural according to the French census bureau rural-urban definitions. Nitrogen dioxide (NO2) concentrations at home addresses were estimated from adjusted land-use regression models as a marker of traffic-related pollution. Associations between NO2 concentrations and PTB were assessed with logistic regression models. Prevalence of PTB was similar among women living in urban (3.2%) and in rural (3.5%) settings. More positive socioeconomic characteristics and health behaviors but more single-parent families were observed among urban women. NO2 exposure averaged 20.8±6.6 µg m(-3) for women residing in urban areas and 18.8±5.6 µg m(-3) for their rural counterparts. A statistically significant increased risk of PTB was observed among women exposed to NO2 concentrations ≥16.4 µg m(-3) and residing in urban areas but not among their rural counterparts. The results of this study, conducted in a region with interspersed urban-rural areas, are in line with previous findings suggesting an increased risk of PTB associated with higher NO2 concentrations for women living in urban areas. The absence of association among their rural counterparts for whom exposure levels were similar suggests that environmental mixtures and psychosocial inequalities might play a role in this heterogeneity. Copyright © 2015 Elsevier Inc. All rights reserved.

Models of antenatal care to reduce and prevent preterm birth: a systematic review and meta-analysis.

PubMed

Fernandez Turienzo, Cristina; Sandall, Jane; Peacock, Janet L

2016-01-12

To assess the effectiveness of models of antenatal care designed to prevent and reduce preterm birth (PTB) in pregnant women. We conducted a search of seven electronic databases and reference lists of retrieved studies to identify trials from inception up to July 2014 where pregnant women, regardless of risk factors for pregnancy complications, were randomly allocated to receive an alternative model of antenatal care or routine care. We pooled risks of PTB to determine the effect of alternative care models in all pregnant women. We also assessed secondary maternal and infant outcomes, women's satisfaction and economic outcomes. 15 trials involving 22,437 women were included. Pregnant women in alternative care models were less likely to experience PTB (risk ratio 0.84, 95% CI 0.74 to 0.96). The subgroup of women randomised to midwife-led continuity models of antenatal care were less likely to experience PTB (0.78, 0.66 to 0.91) but there was no significant difference between this group and women allocated to specialised care (0.92, 0.76 to 1.12) (interaction test for subgroup differences p=0.20). Overall low-risk women in alternative care models were less likely to have PTB (0.74, 0.59 to 0.93), but this effect was not significantly different from that in mixed-risk populations (0.91, 0.79 to 1.05) (subgroup p=0.13). Alternative models of antenatal care for all pregnant women are effective in reducing PTB compared with routine care, but no firm conclusions could be drawn regarding the relative benefits of the two models. Future research should evaluate the impact of antenatal care models which include more recent interventions and predictive tests, and which also offer continuity of care by midwives throughout pregnancy. CRD42014007116. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Real-Life Clinical Practice of Using the Xpert MTB/RIF Assay in Thailand.

PubMed

Kawkitinarong, Kamon; Suwanpimolkul, Gompol; Kateruttanakul, Pairaj; Manosuthi, Weerawat; Ubolyam, Sasiwimol; Sophonphan, Jiratchaya; Avihingsanon, Anchalee; Ruxrungtham, Kiat

2017-05-15

Delayed diagnosis of tuberculosis (TB) and drug-resistant TB are major challenges of TB control in Thailand. This study assessed the practicality of the Xpert MTB/RIF assay in a real-life setting with high prevalence of human immunodeficiency virus (HIV) infection and pulmonary tuberculosis (PTB). This prospective study was conducted at 3 large tertiary care hospitals. Patients who had suspected PTB were enrolled into the study. Expectorated sputum samples were sent for staining, mycobacterial culture, and Xpert MTB/RIF. Four hundred ninety-four patients were enrolled. From 355 cases with final diagnosis of PTB, 263 (71.8%) had definite diagnosis and 92 cases had probable diagnosis. Among TB culture-positive cases, Xpert MTB/RIF had 100% and 81% sensitivity in sputum smear-positive and smear-negative groups, respectively. The specificity was 95.7%. The sensitivity and positive predictive value of Xpert MTB/RIF in culture-negative but clinically diagnosed PTB was 37.8% and 83.8%, respectively. Centrifugation was required in 59% cases with scanty sputum. Five cases were false-positive by Xpert MTB/RIF in patients with nontuberculous mycobacteria, old PTB scar, and immune reconstitution syndrome. Discordant rifampicin susceptibility results of Xpert MTB/RIF and mycobacteria growth indicator tube (MGIT) were confirmed by using rpoB gene sequencing, which raised the sensitivity of Xpert MTB/RIF in detecting rifampicin resistance to 93.8%. Xpert MTB/RIF is an effective tool in diagnosing PTB but will be more cost-effective for sputum-negative patients and in settings with high prevalence of rifampicin resistance. Early diagnosis of TB results in early treatment and implementation of strategies to limit spreading of TB. Sputum centrifugation may increase the yield of Xpert MTB/RIF. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Discordance between MTB/RIF and Real-Time Tuberculosis-Specific Polymerase Chain Reaction Assay in Bronchial Washing Specimen and Its Clinical Implications.

PubMed

Jo, Yong Suk; Park, Ju-Hee; Lee, Jung Kyu; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Kyeom

2016-01-01

The prevalence and clinical implications of discordance between Xpert MTB/RIF assays and the AdvanSure TB/NTM real-time polymerase chain reaction (PCR) for bronchial washing specimens have not been studied in pulmonary TB (PTB) patients. The discordant proportion and its clinical impact were evaluated in 320 patients from the bronchoscopy registry whose bronchial washing specimens were tested simultaneously with Xpert MTB/RIF and the TB/NTM PCR assay for three years, and the accuracy of the assays, including the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were studied. The clinical risk factors for discordance and false positivity of assays were also studied. Among 130 patients who were clinically diagnosed with PTB, 64 patients showed positive acid-fast bacilli culture results, 56 patients showed positive results in molecular methods and clinician diagnosed PTB without results of microbiology in 10 patients. The sensitivity, specificity, PPV, and NPV were 80.0%, 98.95%, 98.1%, and 87.9%, respectively, for Xpert MTB/RIF and 81.5%, 92.6%, 88.3%, and 88.0%, respectively, for TB/NTM PCR. The discordant proportion was 16.9% and was higher in culture-negative PTB compared to culture-confirmed PTB (24.3% vs. 9.4%, p = 0.024). However, there were no significant differences in the clinical characteristics, regardless of the discordance. The diagnostic yield increased with an additional assay (7.7% for Xpert MTB/RIF and 9.2% for TB/NTM PCR). False positivity was less common in patients tested with Xpert MTB/RIF (1.05% vs. 7.37%, p = 0.0035). No host-related risk factor for false positivity was identified. The Xpert MTB/RIF and TB/NTM PCR assay in bronchial washing specimens can improve the diagnostic yields for PTB, although there were considerable discordant results without any patient-related risk factors.

Association of Pre-Pregnancy Body Mass Index and Gestational Weight Gain with Preterm Births and Fetal Size: an Observational Study from Lebanon.

PubMed

El Rafei, Rym; Abbas, Hussein A; Charafeddine, Lama; Nakad, Pascale; Al Bizri, Ayah; Hamod, Dany; Yunis, Khalid A

2016-01-01

Pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are reported to impact the preterm birth (PTB) rate and newborn size. Most studies have been conducted in developed countries, although PTB and adverse pregnancy outcomes are more frequent in the developing world. The aim of this study is to elucidate the association of pre-pregnancy BMI and GWG on the occurrence of PTB and sub-optimal fetal size in Lebanon. This is a retrospective cohort study using a hospital-based register covering 35% of births in Lebanon between 2001 and 2012. Data were collected on 170 428 pregnancies from 32 hospitals using medical records and interviews. After adjusting for confounders, underweight women had increased odds of having very preterm [odds ratio (OR) 1.58, 95% confidence interval (CI) 1.16, 2.14], preterm (OR 1.42, 95% CI 1.28, 1.58), and small for gestational age (SGA) (OR 1.50, 95% CI 1.37, 1.63) neonates. When BMI was analysed with GWG, only SGA remained significant in underweight women with low GWG. For all BMI groups, low GWG was protective against large for gestational age (LGA) and high GWG increased the odds of LGA. GWG, both low (OR 1.25, 95% CI 1.15, 1.35) and high (OR 1.43, 95% CI 1.32, 1.55) increased the risk of PTB in normal weight women. The same result was obtained for overweight women. High GWG increased the risk of LGA for all groups and PTB in normal weight and overweight women, whereas low GWG increased the risk of SGA and PTB. Given that there are not many studies from middle income/developing countries on patterns of weight gain during pregnancy, findings from this study may help with pre-conception counselling with emphasis on the importance of an optimal pre-pregnancy BMI and appropriate weight gain during pregnancy. © 2015 John Wiley & Sons Ltd.

Long working hours and pregnancy complications: women physicians survey in Japan.

PubMed

Takeuchi, Masumi; Rahman, Mahbubur; Ishiguro, Aya; Nomura, Kyoko

2014-07-23

Previous studies have investigated the impact of occupational risk factors on health outcomes among physicians. However, few studies have investigated the effects on pregnancy outcomes among physicians. In this study, we examined the association between working hours during pregnancy and pregnancy complications among physicians. A cross-sectional study was based on a survey conducted in 2009-2011 of 1,684 alumnae (mean age, 44 ± 8 years) who had graduated from 13 private medical schools in Japan. Data on threatened abortion (TA), preterm birth (PTB), and the number of working hours during the first trimester of pregnancy were obtained via retrospective assessments. Of the 939 physicians with a first pregnancy, 15% experienced TA and 12% experienced PTB. Women who experienced TA (mean weekly working hours: 62 h vs. 50 h, P < .0001) or PTB (62 h vs. 50 h, P < .0001) had longer weekly working hours during the first trimester than did those without pregnancy complications. Compared with women who worked 40 hours or less per week, women who worked 71 hours or more per week had a three-fold higher risk of experiencing TA (95% confidence interval (CI): 1.7-6.0) even after adjusting for medical specialty, maternal age, and current household income. The risk of experiencing PTB was 2.5 times higher (95% CI:1.2-5.2) in women who worked 51-70 hours and 4.2 times higher (95% CI: 1.9-9.2) in women who worked 71 hours or more even after adjusting for specialty, maternal age, and current household income. The trend in the P statistic reflecting the effect of the quartile of hours worked per week (40 hours, 41-50 hours, 51-70 hours, ≥ 71 hours) on TA or PTB was 0.0001 in the multivariate logistic regression models. These results suggest that working long hours during the first trimester of pregnancy is associated with TA and PTB.

Microconchids from microbialite ecosystem immediately after end-Permian mass extinction: ecologic selectivity and implications for microbialite ecosystem structure

NASA Astrophysics Data System (ADS)

Yang, H.; Chen, Z.; Wang, Y. B.; Ou, W.; Liao, W.; Mei, X.

2013-12-01

The Permian-Triassic (P-Tr) carbonate successions are often characterized by the presence of microbialite buildups worldwide. The widespread microbialites are believed as indication of microbial proliferation immediately after the P-Tr mass extinction. The death of animals representing the primary consumer trophic structure of marine ecosystem in the P-Tr crisis allows the bloom of microbes as an important primary producer in marine trophic food web structure. Thus, the PTB microbialite builders have been regarded as disaster taxa of the P-Tr ecologic crisis. Microbialite ecosystems were suitable for most organisms to inhabit. However, increasing evidence show that microbialite dwellers are also considerably abundant and diverse, including mainly foraminifers Earlandia sp. and Rectocornuspira sp., lingulid brachiopods, ostrocods, gastropods, and microconchids. In particular, ostracods are extremely abundant in this special ecosystem. Microconchid-like calcareous tubes are also considerably abundant. Here, we have sampled systematically a PTB microbialite deposit from the Dajiang section, southern Guizhou Province, southwest China and have extracted abundant isolated specimens of calcareous worm tubes. Quantitative analysis enables to investigate stratigraphic and facies preferences of microconchids in the PTB microbialites. Our preliminary result indicates that three microconchid species Microconchus sp., Helicoconchus elongates and Microconchus aberrans inhabited in microbialite ecosystem. Most microconchilds occurred in the upper part of the microbialite buildup and the grainstone-packstone microfacies. Very few microconchilds were found in the rocks bearing well-developed microbialite structures. Their stratigraphic and environmental preferences indicate proliferation of those metazoan organisms is coupled with ebb of the microbialite development. They also proliferated in some local niches in which microbial activities were not very active even if those microconchids occur in the PTB microbialite buildups. In addition, the combination of previously published data and present studies indicates that the PTB microbialite ecosystem contained much higher biodiversity than previously expected. The PTB microbialite ecosystems provided habitable niches for some particular fossil groups to survive the P-Tr mass extinction.

A high resolution magnetostratigraphic profile across the Permian-Triassic boundary in the Southern Sydney Basin, eastern Australia

NASA Astrophysics Data System (ADS)

Belica, M. E.; Tohver, E.; Nicoll, R.; Denyszyn, S. W.; Pisarevsky, S.; George, A. D.

2016-12-01

The Permian-Triassic boundary (PTB) is associated with the largest mass extinction in Phanerozoic geologic history. Despite several decades of intense study, there is ongoing debate regarding the exact timing of extinction and the global correlation of marine and terrestrial P-T sections. The terrestrial record is hampered by a lack of index fossils; however, magnetostratigraphy offers an opportunity for correlation because it relies on the global synchronicity of magnetic reversals. A magnetostratigraphic profile across the Permian-Triassic boundary has been obtained from a stratigraphically continuous terrestrial section in the Southern Sydney Basin of eastern Australia. The 60 m section is located within the Narrabeen Group, which consists of fluvial to lacustrine sandstones and mudstones. Paleomagnetic samples were collected at one meter intervals to determine a detailed reversal record. Samples were stepwise thermally demagnetized to isolate a primary remanence, and magnetic susceptibility was measured in the field at 30 cm intervals with values ranging from -0.047-2.50 (10-3 SI units). Three normal and three reverse magnetozones were detected after removal of a low temperature overprint, and the results show good agreement with the Global Magnetic Polarity Timescale as well as marine Permian-Triassic sections where the PTB is well constrained. Furthermore, a reverse polarity subchron has been identified within the normal magnetozone spanning the PTB similar to results published from the Netherlands and China. The magnetic stratigraphy suggests that the Narrabeen Group was deposited during the late Changhsingian to early Induan, and provides a revised placement of the PTB in the lower Wombarra Claystone. Integration of the magnetostratigraphy with existing isotopic datasets suggests that the terrestrial extinction in eastern Australia occurred 7.5 m below the PTB in the Changhsingian Coalcliff Sandstone. A tuff within a coal seam underlying the Coalcliff Sandstone has a published age of 252.6 ± 0.3 Ma, which constrains the extinction level to no more than 700 kyr older than the PTB.

Intimate partner violence during pregnancy and its association with preterm birth and low birth weight in Tanzania: A prospective cohort study

PubMed Central

Mushi, Declare; Meyrowitsch, Dan Wolf; Manongi, Rachel; Rogathi, Jane Januarius; Gammeltoft, Tine; Rasch, Vibeke

2017-01-01

Introduction Intimate partner violence (IPV) is a public health problem that affects millions of women worldwide. The role of violence as an underlying factor in poor birth outcomes remains an area where strong evidence is lacking. The aim of this study was to determine the association between intimate partner violence (IPV) and preterm delivery (PTB) and low birth weight (LBW). Materials and methods A prospective cohort study was conducted among 1112 pregnant women attending antenatal care in Moshi–Tanzania. The women were enrolled before 24 weeks gestation, followed-up at week 34 to determine exposure to violence during pregnancy, and after delivery to estimate gestation age at delivery and birth weight. Logistic regression analysis was performed to assess the association between exposure to IPV during pregnancy and PTB and LBW while adjusting for possible confounders. In addition, stratified analysis based on previous history of adverse pregnancy outcome was performed. Results One-third of the women experienced IPV during pregnancy, 22.3% reported emotional, 15.4% sexual and 6.3% physical violence. Women exposed to physical IPV were three times more likely to experience PTB (AOR = 2.9; CI 95%: 1.3–6.5) and LBW (AOR = 3.2; CI 95%: 1.3–7.7). Women with previous adverse pregnancy outcomes and exposure to physical IPV had a further increased risk of PTB (AOR = 4.5; CI 95%: 1.5–13.7) and LBW (AOR = 4.8; CI 95%: 1.6–14.8) compared to those without previous history of adverse outcome. Conclusion Women who are exposed to IPV during pregnancy are at increased risk of PTB and LBW. The risk is even stronger if the women additionally have suffered a previous adverse pregnancy outcome. Interventions addressing IPV are urgently needed to prevent occurrence and reoccurrence of PTB and LBW. PMID:28235031

Involving private practitioners in the Indian tuberculosis programme: a randomised trial.

PubMed

Yellappa, Vijayashree; Battaglioli, Tullia; Gurum, Sanath Kumar; Narayanan, Devadasan; Van der Stuyft, Patrick

2018-05-01

To assess a multicomponent intervention to improve private practitioners (PPs) involvement in referral of presumptive pulmonary TB (PTB) cases to the Revised National TB Control Programme (RNTCP) for sputum examination. Randomised controlled trial. We randomly allocated all 189 eligible PPs in Tumkur city, South India, to intervention or control arm. The intervention, implemented between December 2014 and January 2016, included two sets of activities, one targeted at health system strengthening (building RNTCP staff capacity to collaborate with PPs, provision of feedback on referrals through SMS) and one targeted at intervention PPs (training in RNTCP, provision of referral pads and education materials and monthly visits to PPs by RNTCP staff). Crude and adjusted referral and PTB case-finding rate ratios were calculated with negative binomial regression. PPs referred 836 individuals (548 from intervention and 169 from control arm PPs) of whom 176 were diagnosed with bacteriologically confirmed PTB. The proportion (95% confidence interval) of referring PPs [0.59 (0.49, 0.68) vs. 0.42 (0.32, 0.52) in the intervention and control arm, respectively], mean referral rate per PP-year [(5.7 (3.8, 8.7) vs. 1.8 (1.2, 2.8)] and smear-positive PTB case-finding rate per PP-year [(1.5 (0.9, 2.2) vs. 0.6 (0.3, 0.9)] were significantly higher in the intervention than the control arm. Stratifying by qualification, a statistically significant difference in the above indicators remained only among GPs and internists. Overall, surgeons, paediatricians and gynaecologists referred few patients. PP referrals contributed to 20% of the sputum smear positive PTB cases detected by RNTCP in Tumkur city (14% were from intervention arm PPs). We demonstrated the effectiveness of a health system-oriented intervention to improve PP's referrals of presumptive PTB cases to RNTCP. © 2018 John Wiley & Sons Ltd.

Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population.

PubMed

Wu, Linlin; Hu, Yi; Li, Dange; Jiang, Weili; Xu, Biao

2015-04-01

We investigated whether polymorphisms in the toll-like receptor genes or gene-gene interactions are associated with susceptibility to latent tuberculosis infection (LTBI) or subsequent pulmonary tuberculosis (PTB) in a Chinese population. Two matched case-control studies were undertaken. Previously reported polymorphisms in the toll-like receptors (TLRs) were compared between 422 healthy controls (HC) and 205 LTBI patients and between 205 LTBI patients and 109 PTB patients, to assess whether these polymorphisms and their interactions are associated with LTBI or PTB. A PCR-based restriction fragment length polymorphism analysis was used to detect genetic polymorphisms in the TLR genes. Nonparametric multifactor dimensionality reduction (MDR) was used to analyze the effects of interactions between complex disease genes and other genes or environmental factors. Sixteen markers in TLR1, TLR2, TLR4, TLR6, TLR8, TLR9, and TIRAP were detected. In TLR2, the frequencies of the CC genotype (OR = 2.262; 95% CI: 1.433-3.570) and C allele (OR = 1.566; 95% CI: 1.223-1.900) in single-nucleotide polymorphism (SNP) rs3804100 were significantly higher in the LTBI group than in the HC group, whereas the GA genotype of SNP rs5743708 was associated with PTB (OR = 6.087; 95% CI: 1.687-21.968). The frequencies of the GG genotype of SNP rs7873784 in TLR4 (OR = 2.136; 95% CI: 1.312-3.478) and the CC genotype of rs3764879 in TLR8 (OR = 1.982; 95% CI: 1.292-3.042) were also significantly higher in the PTB group than in the HC group. The TC genotype frequency of SNP rs5743836 in TLR9 was significantly higher in the LTBI group than in the HC group (OR = 1.664; 95% CI: 1.201-2.306). An MDR analysis of gene-gene and gene-environment interactions identified three SNPs (rs10759932, rs7873784, and rs10759931) that predicted LTBI with 84% accuracy (p = 0.0004) and three SNPs (rs3804100, rs1898830, and rs10759931) that predicted PTB with 80% accuracy (p = 0.0001). Our results suggest that genetic variation in TLR2, 4, 8 and 9, implicating TLR-related pathways affecting the innate immunity response, modulate LTBI and PTB susceptibility in Chinese.

Smear-positive pulmonary tuberculosis and AFB examination practices according to the standard checklist of WHO's tuberculosis laboratory assessment tool in three governmental hospitals, Eastern Ethiopia.

PubMed

Mekonnen, Abiyu

2014-05-13

Using the Directly Observed Treatment-Short course (DOTS) program the World Health Organization's global target was to detect 70% of new sputum-smear positive PTB cases. Smear positive PTB cases are more infectious than the smear negative cases. The TB case detection rate remains very low in Ethiopia, but there are increases in smear-negative PTB diagnosis which could be attributed to several factors including poor quality of sputum smear-microscopy. A five years retrospective record review of data between September, 2007 and August, 2012 and an in-depth assessment of AFB staining practices of sputum smear using a standard checklist were made. The proportion of smear positive cases relative to overall Acid Fast Bacilli (AFB) screened was determined over a five year period to indicate the overall prevalence and the trend. Odds ratio with 95 percent confidence interval was calculated for categorical variables using multivariate Logistic Regression model to assess the strength of association. A total of 1266 individuals' data were reviewed. The majority of the study participants were male, 704 (55.6%), and rural residents, 690 (54.5%). The overall prevalence rate of smear positive PTB was 21.6%. Age categories between 15-24 and 25-34 years were independent predictors of smear positive PTB with adjusted odds ratio of 2.246 [95% CI (1.098-4.597)] and 2.267 [95% CI (1.107-4.642)], respectively. More males were affected by PTB than females with an adjusted odds ratio of 1.426 [95% CI (1.083-1.879)]. An in-depth interview with the respective laboratory chiefs showed that quality control measures for sputum smear microscopy were used at different levels of the testing activities; however, equipment function verification as a quality control measure was not accomplished regularly in all of the study hospital laboratories. The smear positive PTB case detection rate indicated in this study is significantly lower than the countries which met the 70% target of the World Health Organization. Lack of feedback mechanisms in the External Quality Assurance schemes of sputum smear microscopy render the opportunity for improvement difficult; Serial sputum examination showed a considerable rate of positivity in the second sputum sample when compared with the others.

Qualitative assessment of attitudes and knowledge on preterm birth in Malawi and within country framework of care

PubMed Central

2014-01-01

Background The overarching goal of this study was to qualitatively assess baseline knowledge and perceptions regarding preterm birth (PTB) and oral health in an at-risk, low resource setting surrounding Lilongwe, Malawi. The aims were to determine what is understood regarding normal length of gestation and how gestational age is estimated, to identify common language for preterm birth, and to assess what is understood as options for PTB management. As prior qualitative research had largely focused on patient or client-based focused groups, we primarily focused on groups comprised of community health workers (CHWs) and providers. Methods A qualitative study using focus-group discussions, incidence narrative, and informant interviews amongst voluntary participants. Six focus groups were comprised of CHWs, patient couples, midwives, and clinical officers (n = 33) at two rural health centers referring to Kamuzu Central Hospital. Semi-structured questions facilitated discussion of PTB and oral health (inclusive of periodontal disease), including definitions, perception, causation, management, and accepted interventions. Results Every participant knew of women who had experienced “a baby born too soon”, or preterm birth. All participants recognized both an etiology conceptualization and disease framework for preterm birth, distinguished PTB from miscarriage and macerated stillbirth, and articulated a willingness to engage in studies aimed at prevention or management. Identified gaps included: (1) discordance in the definition of PTB (i.e., 28–34 weeks or less than the 8th month, but with a corresponding fetal weight ranging 500 to 2300 grams); (2) utility and regional availability of antenatal steroids for prevention of preterm infant morbidity and mortality; (3) need for antenatal referral for at-risk women, or with symptoms of preterm birth. There was no evident preference for route of progesterone for the prevention of recurrent PTB. Conclusions Qualitative research was useful in (1) identifying gaps in knowledge in urban and rural Malawi, and (2) informing the development of educational materials and implementation of programs or trials ultimately aimed at reducing PTB. As a result of this qualitative work, implementation planning was focused on the gaps in knowledge, dissemination of knowledge (to both patients and providers), and practical solutions to barriers in known efficacious therapies. PMID:24690288

Functional characterization of rare FOXP2 variants in neurodevelopmental disorder.

PubMed

Estruch, Sara B; Graham, Sarah A; Chinnappa, Swathi M; Deriziotis, Pelagia; Fisher, Simon E

2016-01-01

Heterozygous disruption of FOXP2 causes a rare form of speech and language impairment. Screens of the FOXP2 sequence in individuals with speech/language-related disorders have identified several rare protein-altering variants, but their phenotypic relevance is often unclear. FOXP2 encodes a transcription factor with a forkhead box DNA-binding domain, but little is known about the functions of protein regions outside this domain. We performed detailed functional analyses of seven rare FOXP2 variants found in affected cases, including three which have not been previously characterized, testing intracellular localization, transcriptional regulation, dimerization, and interaction with other proteins. To shed further light on molecular functions of FOXP2, we characterized the interaction between this transcription factor and co-repressor proteins of the C-terminal binding protein (CTBP) family. Finally, we analysed the functional significance of the polyglutamine tracts in FOXP2, since tract length variations have been reported in cases of neurodevelopmental disorder. We confirmed etiological roles of multiple FOXP2 variants. Of three variants that have been suggested to cause speech/language disorder, but never before been characterized, only one showed functional effects. For the other two, we found no effects on protein function in any assays, suggesting that they are incidental to the phenotype. We identified a CTBP-binding region within the N-terminal portion of FOXP2. This region includes two amino acid substitutions that occurred on the human lineage following the split from chimpanzees. However, we did not observe any effects of these amino acid changes on CTBP binding or other core aspects of FOXP2 function. Finally, we found that FOXP2 variants with reduced polyglutamine tracts did not exhibit altered behaviour in cellular assays, indicating that such tracts are non-essential for core aspects of FOXP2 function, and that tract variation is unlikely to be a highly penetrant cause of speech/language disorder. Our findings highlight the importance of functional characterization of novel rare variants in FOXP2 in assessing the contribution of such variants to speech/language disorder and provide further insights into the molecular function of the FOXP2 protein.

Perceived Prevalence of Teasing and Bullying Predicts High School Dropout Rates

ERIC Educational Resources Information Center

Cornell, Dewey; Gregory, Anne; Huang, Francis; Fan, Xitao

2013-01-01

This prospective study of 276 Virginia public high schools found that the prevalence of teasing and bullying (PTB) as perceived by both 9th-grade students and teachers was predictive of dropout rates for this cohort 4 years later. Negative binomial regression indicated that one standard deviation increases in student- and teacher-reported PTB were…

Tamm-Horsfall glycoprotein engages human Siglec-9 to modulate neutrophil activation in the urinary tract

PubMed Central

Patras, Kathryn A.; Coady, Alison; Olson, Joshua; Ali, Syed Raza; RamachandraRao, Satish P.; Kumar, Satish; Varki, Ajit; Nizet, Victor

2017-01-01

Urinary tract infections (UTI) are a major problem in human medicine for which better understanding of native immune defenses may reveal new pathways for therapeutic intervention. Tamm-Horsfall glycoprotein (THP), the most abundant urinary protein, interacts with bacteria including uropathogenic E. coli (UPEC) as well host immune cells. In addition to its well-studied functions to antagonize bacterial colonization, we hypothesize that THP serves a critical host defense function through innate immune modulation. Using isolated human neutrophils, we found that THP binds neutrophils and that this interaction reduces reactive oxygen species generation, chemotaxis, and killing of UPEC. We discovered that THP engages the inhibitory neutrophil receptor sialic acid-binding Ig-like lectin-9 (Siglec-9), and mouse functional ortholog Siglec-E, in a manner dependent on sialic acid on its N-glycan moieties. THP-null mice have significantly more neutrophils present in the urine compared to WT mice, both with and without the presence of inflammatory stimuli. These data support THP as an important negative regulator of neutrophil activation in the urinary tract, with dual functions to counteract bacterial colonization and suppress excessive inflammation within the urinary tract. PMID:28829050

Numb regulates cell–cell adhesion and polarity in response to tyrosine kinase signalling

PubMed Central

Wang, Zezhou; Sandiford, Shelley; Wu, Chenggang; Li, Shawn Shun-Cheng

2009-01-01

Epithelial-mesenchymal transition (EMT), which can be caused by aberrant tyrosine kinase signalling, marks epithelial tumour progression and metastasis, yet the underlying molecular mechanism is not fully understood. Here, we report that Numb interacts with E-cadherin (E-cad) through its phosphotyrosine-binding domain (PTB) and thereby regulates the localization of E-cad to the lateral domain of epithelial cell–cell junction. Moreover, Numb engages the polarity complex Par3–aPKC–Par6 by binding to Par3 in polarized Madin-Darby canine kidney cells. Intriguingly, after Src activation or hepatocyte growth factor (HGF) treatment, Numb decouples from E-cad and Par3 and associates preferably with aPKC–Par6. Binding of Numb to aPKC is necessary for sequestering the latter in the cytosol during HGF-induced EMT. Knockdown of Numb by small hairpin RNA caused a basolateral-to-apicolateral translocation of E-cad and β-catenin accompanied by elevated actin polymerization, accumulation of Par3 and aPKC in the nucleus, an enhanced sensitivity to HGF-induced cell scattering, a decrease in cell–cell adhesion, and an increase in cell migration. Our work identifies Numb as an important regulator of epithelial polarity and cell–cell adhesion and a sensor of HGF signalling or Src activity during EMT. PMID:19609305

Active pulmonary tuberculosis case detection and treatment among floating population in China: an effective pilot.

PubMed

Li, Xinxu; Zhang, Hui; Jiang, Shiwen; Wang, Jia; Liu, Xiaoqiu; Li, Weibin; Yao, Hongyan; Wang, Lixia

2010-12-01

China has more and more floating population because of reform and opening-up. As one of the high burden countries in tuberculosis (TB) control in the world, China has to face more challenges about the TB case detection and treatment among floating population in China. Aim to evaluate the effect of case detection and treatment of the Floating Population TB Control Pilot Project from Global Fund Round Five (GFR5) TB Control Program in China. During October 2006 to September 2008, the pilot project was implemented gradually in 60 counties in Tianjin, Shanghai, Jiangsu, Zhejiang, Fujian, Shandong and Guangdong. All quarterly reports of the pilot project were collected, and these materials were summarized and analyzed. In seven coastal provinces, 19,584 active pulmonary TB (PTB) cases were registered among floating population in 2 years. Among the active PTB cases, 87.2% were 15-45 years old, and 62.8% were male. In second year, 15,629 active PTB cases were registered, and the overall registration rate was 68 per 100,000 people. DOT treatments were provided for 18,125 active PTB cases in 2 years, and overall DOT treatment rate was 92.6%. There were 3,955 active PTB cases registered in first year, and the overall cure rate was 86.0%. Through the implementation of the pilot project, the TB case detection and treatment among floating population have been enhanced in pilot areas of China. The useful experience and results from the pilot project have been being gradually generalized nationally.

Prenatal Depression and Adverse Birth Outcomes: An Updated Systematic Review

PubMed Central

Accortt, Eynav Elgavish; Cheadle, Alyssa C. D.; Schetter, Christine Dunkel

2015-01-01

Complications related to preterm birth (PTB) and low birth weight (LBW) are leading causes of infant morbidity and mortality. Prenatal depression is a hypothesized psychosocial risk factor for both birth outcomes. The purpose of this systematic review was to examine evidence published between 1977 and 2013 on prenatal depression and risks of these primary adverse birth outcomes. A systematic search of the PUBMED and PsycINFO databases was conducted to identify studies testing the associations between prenatal depressive symptoms, or diagnoses of depression, and risk of PTB or LBW. We systematically selected 50 published reports on PTB and length of gestation, and 33 reports on LBW and BW. Results were reviewed by two independent reviewers and we evaluated the quality of the evidence with an established systematic review method, the Newcastle Ottawa Scale. We then undertook a narrative synthesis of the results following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Less than a quarter of 50 published reports found that prenatal depression was significantly associated with PTB or gestational age. In contrast, slightly more than half of the 33 reports found that prenatal depression was associated with LBW or BW. When weighing methodological features, we determined that the effects of prenatal depression on LBW are more consistent than effects on length of gestation or PTB. Although the evidence may not be strong enough to support routine depression screening for risk of adverse outcomes, screening to enable detection and timely treatment to reduce risk of postpartum depression is warranted. Further rigorous research on prenatal depression and adverse birth outcomes is needed. PMID:25452215

Diagnostic Value of Serum Adenosine Deaminase (ADA) Level for Pulmonary Tuberculosis.

PubMed

Salmanzadeh, Shokrollah; Tavakkol, Heshmatollah; Bavieh, Khalid; Alavi, Seyed Mohammad

2015-03-01

Diagnosis of tuberculosis (TB) is not always easy, thus employing methods with a short duration and acceptable sensitivity and specificity is necessary to diagnose TB. The aim of this study was to investigate the diagnostic value of serum adenosine deaminase (ADA) level for diagnosis of pulmonary tuberculosis. A total of 160 sex and age-matched subjects were included in this study, and were divided to four groups; forty patients with pulmonary tuberculosis (PTB) diagnosed based on the national TB program (NTP), forty patients with non-tuberculosis bacterial pneumonia, forty patients with lung cancer and forty people who were healthy in every respect. Serum adenosine deaminase activity in patients of each group was measured by the Giusti and Galanti calorimetry method using a commercial kit (Diazyme, USA). The ANOVA analysis was used to compare groups for quantitative variables. Mean serum ADA level in the PTB group was clearly higher than the mean serum ADA in the other three groups. Mean serum ADA was 26 IU/L in PTB patients, 19.48 IU/L in patients with pneumonia, 15.8 IU/L in patients with lung cancer, and 10.7 IU/L in the control group (P < 0.05). In regard to the cut off value of 26 IU/L for ADA in patients with PTB sensitivity and specificity was defined as 35% and 91%, respectively. Serum ADA activity with high specificity percentage may be a useful alternative test in restricted resource areas to rule out diagnosis of PTB. However, serum ADA activity is not a useful tool for TB diagnosis.

Maternal dental caries and pre-term birth: results from the EPIPAP study.

PubMed

Vergnes, Jean-Noel; Kaminski, Monique; Lelong, Nathalie; Musset, Anne-Marie; Sixou, Michel; Nabet, Cathy

2011-07-01

OBJECTIVE. The aim of this study was to analyse the association between maternal dental caries and pre-term birth (PTB), with a particular focus on the infection-suspected causes of pre-term births. MATERIALS AND METHODS. A secondary analysis was performed on data from the EPIPAP study, a French multi-centre case-control study. Cases were 1107 women giving birth to a singleton live-born infant before 37 weeks of gestation and controls were 1094 women delivering at 37 weeks or more. A sub-group of cases was defined as women with spontaneous labour and/or pre-term premature rupture of membranes (PPROM, n = 620). A full-mouth dental examination was performed after delivery. The main factor of interest was the presence of decay on at least one tooth. RESULTS. Crude associations between presence of tooth decay and PTB or spontaneous PTB/PPROM were significant (OR = 1.21 [1.01-1.45] and OR = 1.25 [1.01-1.55], respectively). After adjustment for two sets of potential confounders (four pre-term birth risk factors and four social characteristics), for periodontitis status and for inter-examiner variability, tooth decay was not significantly associated with either PTB or spontaneous PTB/PPROM (aOR = 1.10 [0.91-1.32] and aOR = 1.14 [0.91-1.42], respectively). CONCLUSIONS. This study failed to demonstrate a significant association between tooth decay and pre-term birth. However, future well-designed studies are needed to further assess the link between dental caries and adverse pregnancy outcomes.

Does additional prenatal care in the home improve birth outcomes for women with a prior preterm delivery? A randomized clinical trial.

PubMed

Lutenbacher, Melanie; Gabbe, Patricia Temple; Karp, Sharon M; Dietrich, Mary S; Narrigan, Deborah; Carpenter, Lavenia; Walsh, William

2014-07-01

Women with a history of a prior preterm birth (PTB) have a high probability of a recurrent preterm birth. Some risk factors and health behaviors that contribute to PTB may be amenable to intervention. Home visitation is a promising method to deliver evidence based interventions. We evaluated a system of care designed to reduce preterm births and hospital length of stay in a sample of pregnant women with a history of a PTB. Single site randomized clinical trial. Eligibility: >18 years with prior live birth ≥20-<37 weeks gestation; <24 weeks gestation at enrollment; spoke and read English; received care at regional medical center. All participants (N = 211) received standard prenatal care. Intervention participants (N = 109) also received home visits by certified nurse-midwives guided by protocols for specific risk factors (e.g., depressive symptoms, abuse, smoking). Data was collected via multiple methods and sources including intervention fidelity assessments. Average age 27.8 years; mean gestational age at enrollment was 15 weeks. Racial breakdown mirrored local demographics. Most had a partner, high school education, and 62% had Medicaid. No statistically significant group differences were found in gestational age at birth. Intervention participants had a shorter intrapartum length of stay. Enhanced prenatal care by nurse-midwife home visits may limit some risk factors and shorten intrapartum length of stay for women with a prior PTB. This study contributes to knowledge about evidence-based home visit interventions directed at risk factors associated with PTB.

Cost and cost effectiveness of vaginal progesterone gel in reducing preterm birth: an economic analysis of the PREGNANT trial.

PubMed

Pizzi, Laura T; Seligman, Neil S; Baxter, Jason K; Jutkowitz, Eric; Berghella, Vincenzo

2014-05-01

Preterm birth (PTB) is a costly public health problem in the USA. The PREGNANT trial tested the efficacy of vaginal progesterone (VP) 8 % gel in reducing the likelihood of PTB among women with a short cervix. We calculated the costs and cost effectiveness of VP gel versus placebo using decision analytic models informed by PREGNANT patient-level data. PREGNANT enrolled 459 pregnant women with a cervical length of 10-20 mm and randomized them to either VP 8 % gel or placebo. We used a cost model to estimate the total cost of treatment per mother and a cost-effectiveness model to estimate the cost per PTB averted with VP gel versus placebo. Patient-level trial data informed model inputs and included PTB rates in low- and high-risk women in each study group at <28 weeks gestation, 28-31, 32-36, and ≥37 weeks. Cost assumptions were based on 2010 US healthcare services reimbursements. The cost model was validated against patient-level data. Sensitivity analyses were used to test the robustness of the cost-effectiveness model. The estimated cost per mother was $US23,079 for VP gel and $US36,436 for placebo. The cost-effectiveness model showed savings of $US24,071 per PTB averted with VP gel. VP gel realized cost savings and cost effectiveness in 79 % of simulations. Based on findings from PREGNANT, VP gel was associated with cost savings and cost effectiveness compared with placebo. Future trials designed to include cost metrics are needed to better understand the value of VP.

Efficient and Stable Ternary Organic Solar Cells Based on Two Planar Nonfullerene Acceptors with Tunable Crystallinity and Phase Miscibility.

PubMed

Wang, Jialin; Peng, Jiajun; Liu, Xiaoyu; Liang, Ziqi

2017-06-21

Planar perylene diimides (PDIs), when used as nonfullerene acceptors for organic photovoltaics, are constrained by their large π-aggregation in solid state. To tackle this issue, another planar nonfullerene acceptor 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone)-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (ITIC) with weak crystallinity and near-infrared light absorption is introduced into the PTB7-Th:PDI binary blend to fabricate efficient and stable ternary solar cells. We have finely tuned the PDI/ITIC weight ratio to investigate the influences of individual ITIC and PDI on the optical, electronic, and morphological properties of the PTB7-Th:ITIC:PDI ternary blend. Compared to the binary blend, complementary optical absorption is achieved in all ternary blends. More importantly, it is found that ITIC plays a critical role on largely suppressing the PDI aggregates in the PTB7-Th:PDI blend, while PDI aids to form an interpenetrating network morphology to facilitate charge transport in the PTB7-Th:ITIC blend. Consequently, when the PDI/ITIC ratio is 3:7 (w/w), the PTB7-Th:ITIC:PDI based inverted solar cells exhibit the highest power conversion efficiency of 8.64% due to their favorable out-of-plane π-π stacking, finest phase-separation morphology, and highest charge mobility. Remarkably, the optimal cells that are solution-processed in air show the promising efficiency of 7.09%, suggesting good ambient stability of such ternary solar cells.

In Situ GIWAXS Analysis of Solvent and Additive Effects on PTB7 Thin Film Microstructure Evolution during Spin Coating

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manley, Eric F.; Strzalka, Joseph; Fauvell, Thomas J.

The influence of solvent and processing additives on the pathways and rates of crystalline morphology formation for spin-coated semiconducting PTB7 (poly[[4,8-bis[(2- ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)- carbonyl]-thieno[3,4-b]thiophenediyl

In Situ GIWAXS Analysis of Solvent and Additive Effects on PTB7 Thin Film Microstructure Evolution during Spin Coating

DOE PAGES

Manley, Eric F.; Strzalka, Joseph; Fauvell, Thomas J.; ...

2017-10-09

The influence of solvent and processing additives on the pathways and rates of crystalline morphology formation for spin-coated semiconducting PTB7 (poly[[4,8-bis[(2- ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)- carbonyl]-thieno[3,4-b]thiophenediyl

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2014-10-01

Shahani B. Peripheral-nerve allotransplantation in rats immunosuppressed with transient or long-term FK-506. Journal of reconstructive microsurgery ...multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions . Microsurgery . 2012 Jan;32(1):1-14. PubMed PMID: 22121093...PTB method can provide fixation strengths 6 approaching that of conventional microsurgery and that the PTB repair is unlikely to be disturbed in

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2013-10-01

can provide fixation strengths approaching that of conventional microsurgery and that the PTB repair is unlikely to be disturbed in vivo. The...of nerve wrap biomaterial during long periods of recovery associated with large nerve deficit reconstruction and long nerve grafts. As with the...PTB/xHAM wrap compared to standard (suture) of care microsurgery . Demonstrated improved nerve regeneration in a muscle mass retention model

Exposure to fine particulate matter during pregnancy and risk of preterm birth among women in New Jersey, Ohio, and Pennsylvania, 2000-2005

EPA Science Inventory

BACKGROUND: Particulate matter ≤ 2.5 um in aerodynamic diameter (PM2.5) has been variably associated with preterm birth (PTB). • OBJECTIVE: We classified PTB into four categories (20-27, 28-31, 32-34, and 35-36 weeks completed gestation) and estimated risk differences (RDs) f...

Psychosocial stress in pregnancy and preterm birth: associations and mechanisms

PubMed Central

Shapiro, Gabriel D.; Fraser, William D.; Frasch, Martin G.; Séguin, Jean R.

2016-01-01

Aims Psychosocial stress during pregnancy (PSP) is a risk factor of growing interest in the etiology of preterm birth (PTB). This literature review assesses the published evidence concerning the association between PSP and PTB, highlighting established and hypothesized physiological pathways mediating this association. Method The PubMed and Web of Science databases were searched using the keywords “psychosocial stress”, “pregnancy”, “pregnancy stress”, “preterm”, “preterm birth”, “gestational age”, “anxiety”, and “social support”. After applying the exclusion criteria, the search produced 107 articles. Results The association of PSP with PTB varied according to the dimensions and timing of PSP. Stronger associations were generally found in early pregnancy, and most studies demonstrating positive results found moderate effect sizes, with risk ratios between 1.2 and 2.1. Subjective perception of stress and pregnancy-related anxiety appeared to be the stress measures most closely associated with PTB. Potential physiological pathways identified included behavioral, infectious, neuroinflammatory, and neuroendocrine mechanisms. Conclusions Future research should examine the biological pathways of these different psychosocial stress dimensions and at multiple time points across pregnancy. Culture-independent characterization of the vaginal microbiome and noninvasive monitoring of cholinergic activity represent two exciting frontiers in this research. PMID:24216160

Chronic airway obstruction after successful treatment of tuberculosis and its impact on quality of life.

PubMed

de la Mora, I Laniado; Martínez-Oceguera, D; Laniado-Laborín, R

2015-07-01

Tuberculosis (TB) clinic in Tijuana, México. Chronic airway obstruction (CAO) can be a sequella of pulmonary tuberculosis (PTB), independently of smoking history. To determine the prevalence of CAO in subjects recently recorded as cured after treatment of PTB, and its impact on quality of life. Cross-sectional study. Overall, 34.3% of patients with a history of PTB had non-reversible CAO, defined as FEV1 <70% post-bronchodilator. Subjects with CAO had significantly more radiographic fibrocavitary sequellae on chest X-rays, more extensive changes (1.8 ± 0.8 affected quadrants vs. 1.3 ± 0.6, P = 0.04), more residual lung cavities (1.4 ± 0.8 vs. 0.5 ± 0.7, P = 0.002), and greater mediastinal retraction (42.4% vs. 16.7%, P = 0.026). The mean COPD Assessment Test score for subjects with CAO was 15.1 ± 10.4. The prevalence of irreversible CAO using the lower limit of normal criteria was higher (40%) than that calculated with fixed ratio criteria (34.3%). Functional abnormalities are frequently already present at the end of treatment for PTB; patients with CAO are often symptomatic and experience a significant impact on quality of life.

Analysis of amino acids and acyl carnitine profiles in low birth weight, preterm, and small for gestational age neonates.

PubMed

Liu, Qian; Wu, Jing; Shen, Wen; Wei, Ran; Jiang, Jianhui; Liang, Jinqun; Chen, Min; Zhong, Mei; Yin, Aihua

2017-11-01

To analyze the amino acids (AA) and acyl carnitine (AC) profiles in dry blood spot (DBS) specimens of low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA), and to compare the concentration difference of AA and AC with those without above. This is a retrospectively study. Eight thousand nine hundred and seventy-nine uncomplicated pregnant newborns were enrolled into the study. DBS were collected on the third day of life, and concentrations of 11 types of AA, free carnitine and 30 types of AC were detected by using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS). Shapiro-Wilk test and Kruskal-Wallis rank test were applied in statistical analysis. Concentrations of most AA and AC in infants born in SGA were significantly higher than those in non-SGA group, while lower in LBW and PTB groups than those in non-LBW and non-PTB groups (p < 0.05). The difference of concentration of AA and AC in the subgroups suggested there may be a dysutilization of AA and AC in SGA, but an inborn insufficient of AA and AC in LBW and PTB neonates.

Pitfalls using tyramide signal amplification (TSA) in the mouse gastrointestinal tract: endogenous streptavidin-binding sites lead to false positive staining.

PubMed

Horling, L; Neuhuber, W L; Raab, M

2012-02-15

Highly sensitive immunohistochemical detection systems such as tyramide signal amplification (TSA) are widely used, since they allow using two primary antibodies raised in the same species. Most of them are based on the streptavidin-biotin-peroxidase system and include streptavidin-coupled secondary antibodies. Using TSA in cryostat-sectioned tissues of mouse esophagus, we were puzzled by negative controls with unexpected staining mostly in the ganglionic areas. This prompted us to search for the causing agent and to include also other parts of the mouse gastrointestinal tract for comparison. Streptavidin-coupled antibodies bound to endogenous binding sites yet to be characterized, which are present throughout the mouse intestines. Staining was mainly localized around neuronal cell bodies of enteric ganglia. Thus, caution is warranted when applying streptavidin-coupled antibodies in the mouse gastrointestinal tract. The use of endogenous biotin-blocking kits combined with a prolonged post-fixation time could significantly reduce unintentional staining. Copyright © 2011 Elsevier B.V. All rights reserved.

Expression of Ciona intestinalis Variable Region-Containing Chitin-Binding Proteins during Development of the Gastrointestinal Tract and Their Role in Host-Microbe Interactions

PubMed Central

Liberti, Assunta; Melillo, Daniela; Zucchetti, Ivana; Natale, Lenina; Dishaw, Larry J.; Litman, Gary W.; De Santis, Rosaria; Pinto, Maria Rosaria

2014-01-01

Variable region-containing chitin-binding proteins (VCBPs) are secreted, immune-type molecules that have been described in both amphioxus, a cephalochordate, and sea squirt, Ciona intestinalis, a urochordate. In adult Ciona, VCBP-A, -B and -C are expressed in hemocytes and the cells of the gastrointestinal tract. VCBP-C binds bacteria in the stomach lumen and functions as an opsonin in vitro. In the present paper the expression of VCBPs has been characterized during development using in situ hybridization, immunohistochemical staining and quantitative polymerase chain reaction (qPCR) technologies. The expression of VCBP-A and -C is detected first in discrete areas of larva endoderm and becomes progressively localized during differentiation in the stomach and intestine, marking the development of gut tracts. In “small adults” (1–2 cm juveniles) expression of VCBP-C persists and VCBP-A gradually diminishes, ultimately replaced by expression of VCBP-B. The expression of VCBP-A and -C in stage 7–8 juveniles, at which point animals have already started feeding, is influenced significantly by challenge with either Gram-positive or -negative bacteria. A potential role for VCBPs in gut-microbiota interactions and homeostasis is indicated. PMID:24788831

Use of Mueller matrix colposcopy in the characterization of cervical collagen anisotropy

NASA Astrophysics Data System (ADS)

Montejo, Karla A.; Chue-Sang, Joseph; Bai, Yuqiang; Stoff, Susan; Holness, Nola; Gonzalez, Mariacarla; Gomes, Jefferson; Gandjbakhche, Amir; Chernomordik, Viktor V.; Ramella-Roman, Jessica C.

2017-02-01

Preterm birth (PTB) presents a serious medical heath concern in both economically developed and developing nations, with incidence rate from 15%-11% respectively. Changes in cervical collagen bundle orientation and distribution may prove to be a predictor of PTB. Polarization imaging is an effective means to measure optical anisotropy in birefringent biological tissue such as those rich in collagen. Non-invasive, full-field Mueller Matrix polarimetry (MMP) imaging methodologies, optical coherence tomography (OCT), and second harmonic generation (SHG) microscopy were used to assess cervical collagen content and structure in non-pregnant cervices. In vivo studies using a Mueller Matrix colposcope are underway. Further studies of cervical collagen orientation throughout pregnancy are needed to understand if Mueller matrix polarimetry can effectively identify at-risk conditions for PTB.

The male genital tract is not a pharmacological sanctuary from efavirenz.

PubMed

Avery, L B; Bakshi, R P; Cao, Y J; Hendrix, C W

2011-07-01

Many antiretroviral (ARV) drugs have large blood plasma-to-seminal plasma (BP/SP) concentration ratios. Concern exists that these drugs do not adequately penetrate the male genital tract (MGT), resulting in the MGT becoming a "pharmacological sanctuary" from these agents, with ineffective MGT concentrations despite effective blood concentrations. Efavirenz (EFV) is the most highly protein-bound ARV drug, with >99% binding in blood plasma and the largest BP/SP total EFV concentration ratio, reportedly ranging from 11 to 33. To evaluate protein binding as an explanation for the differences between the drug concentrations in blood and semen, we developed a novel ultrafiltration method, corrected for the duration of centrifugation, to measure protein binding in the two matrices. In six subjects, protein-free EFV concentrations were the same in blood and semen; the median (interquartile range (IQR)) protein-free EFV SP/BP ratio was 1.21 (0.99-1.35); EFV protein binding was 99.82% (99.79-99.86) in BP and 95.26% (93.24-96.67) in SP. This shows that the MGT is not a sanctuary from EFV.

Quantitative fetal fibronectin and cervical length in symptomatic women: results from a prospective blinded cohort study.

PubMed

Levine, Lisa D; Downes, Katheryne L; Romero, Julie A; Pappas, Hope; Elovitz, Michal A

2018-05-15

Our objectives were to determine whether quantitative fetal fibronectin (fFN) and cervical length (CL) screening can be used alone or in combination as prognostic tests to identify symptomatic women at the highest or lowest risk for spontaneous preterm birth (sPTB). A prospective, blinded cohort study of women presenting with a singleton gestation to our triage unit between 22-33w6d with preterm labor symptoms was performed. Women with ruptured membranes, moderate/severe bleeding, and dilation >2 cm were excluded. The primary outcome was sPTB <37 weeks. We evaluated test characteristics of quantitative fFN and CL assessment, both separately and in combination, considering traditionally reported cut-points (fFN ≥50 and CL <25), as well as cut-points above and below these measures. We found interactions between fFN >50 and CL <25 and sPTB by parity and obstetric history (p < .05) and therefore stratified results. Test characteristics are presented with positive predictive value (PPV) and negative predictive value (NPV). Five hundred eighty women were enrolled and 537 women were available for analysis. Overall sPTB rate was 11.1%. Among nulliparous women, increasing levels of fFN were associated with increasing risk of sPTB, with PPV going from 26.5% at ≥20 ng/mL to 44.4% at ≥200 ng/mL. A cut-point of 20 ng/mL had higher sensitivity (69.2%) and higher NPV (96.8%) and therefore identified a "low-risk" group. fFN was not informative for multiparous women regardless of prior obstetrical history or quantitative level chosen. For all women, a shorter CL was associated with an increased sPTB risk. Among nulliparas and multiparas without a prior sPTB, a CL <20 mm optimized test characteristics (PPV 25 and 20%, NPV 95.5, and 92.7%, respectively). For multiparas with a prior sPTB, CL <25 mm was more useful. Using fFN and CL in combination for nulliparas did not improve test characteristics over using the individual fFN (p = .74) and CL (p = .31) components separately. This study identifies the importance of stratifying by parity and obstetrical history when using screening modalities for risk assessment in symptomatic women. For nulliparous women, either quantitative fFN or cervical length assessment can be utilized, depending on resources available, but a lower cut-point of 20 ng/mL should be used for quantitative fFN. For multiparous women, fFN is not useful and cervical length assessment should be the main screening tool utilized when there is clinical uncertainty. Regardless of parity, the PPV of fFN and CL is low and therefore the greatest clinical utility remains in its NPV.

Recognition of the 3′ splice site RNA by the U2AF heterodimer involves a dynamic population shift

PubMed Central

Voith von Voithenberg, Lena; Sánchez-Rico, Carolina; Kang, Hyun-Seo; Madl, Tobias; Zanier, Katia; Barth, Anders; Warner, Lisa R.; Sattler, Michael; Lamb, Don C.

2016-01-01

An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3′ splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands. To investigate the molecular mechanism and dynamics of 3′ splice site recognition by U2AF65 and the role of U2AF35 in the U2AF heterodimer, we have combined single-pair FRET and NMR experiments. In the absence of RNA, the RRM1,2 domain arrangement is highly dynamic on a submillisecond time scale, switching between closed and open conformations. The addition of Py-tract RNA ligands with increasing binding affinity (strength) gradually shifts the equilibrium toward an open conformation. Notably, the protein–RNA complex is rigid in the presence of a strong Py-tract but exhibits internal motion with weak Py-tracts. Surprisingly, the presence of U2AF35, whose UHM domain interacts with U2AF65 RRM1, increases the population of the open arrangement of U2AF65 RRM1,2 in the absence and presence of a weak Py-tract. These data indicate that the U2AF heterodimer promotes spliceosome assembly by a dynamic population shift toward the open conformation of U2AF65 to facilitate the recognition of weak Py-tracts at the 3′ splice site. The structure and RNA binding of the heterodimer was unaffected by cancer-linked myelodysplastic syndrome mutants. PMID:27799531

Phosphorylated c-Mpl tyrosine 591 regulates thrombopoietin-induced signaling.

PubMed

Sangkhae, Veena; Saur, Sebastian Jonas; Kaushansky, Alexis; Kaushansky, Kenneth; Hitchcock, Ian Stuart

2014-06-01

Thrombopoietin (TPO) is the primary regulator of platelet production, affecting cell survival, proliferation, and differentiation through binding to and stimulation of the cell surface receptor the cellular myeloproliferative leukemia virus oncogene (c-Mpl). Activating mutations in c-Mpl constitutively stimulate downstream signaling pathways, leading to aberrant hematopoiesis, and contribute to development of myeloproliferative neoplasms. Several studies have mapped the tyrosine residues within the cytoplasmic domain of c-Mpl that mediate these cellular signals; however, secondary signaling pathways are incompletely understood. In this study, we focused on c-Mpl tyrosine 591 (Y591). We found Y591 of wild-type c-Mpl to be phosphorylated in the presence of TPO. Additionally, eliminating Y591 phosphorylation by mutation to Phe resulted in decreased total receptor phosphorylation. Using a Src homology 2/phosphotyrosine-binding (SH2/PTB) domain binding microarray, we identified novel c-Mpl binding partners for phosphorylated Y591, including Src homology region 2 domain-containing phosphatase-1 (SHP-1), spleen tyrosine kinase (SYK) and Bruton's tyrosine kinase (BTK). The functional significance of binding partners was determined through small interfering RNA treatment of Ba/F3-Mpl cells, confirming that the increase in pERK1/2 resulting from removal of Y591 may be mediated by spleen tyrosine kinase. These findings identify a novel negative regulatory pathway that controls TPO-mediated signaling, advancing our understanding of the mechanisms required for successful maintenance of hematopoietic stem cells and megakaryocyte development. Copyright © 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Epigenetic regulation of lncRNA connects ubiquitin-proteasome system with infection-inflammation in preterm births and preterm premature rupture of membranes.

PubMed

Luo, Xiucui; Pan, Jing; Wang, Leilei; Wang, Peirong; Zhang, Meijiao; Liu, Meilin; Dong, Ziqing; Meng, Qian; Tao, Xuguang; Zhao, Xinliang; Zhong, Julia; Ju, Weina; Gu, Yang; Jenkins, Edmund C; Brown, W Ted; Shi, Qingxi; Zhong, Nanbert

2015-02-15

Preterm premature rupture of membranes (PPROM) is responsible for one third of all preterm births (PTBs). We have recently demonstrated that long noncoding RNAs (lncRNAs) are differentially expressed in human placentas derived from PPROM, PTB, premature rupture of the membranes (PROM), and full-term birth (FTB), and determined the major biological pathways involved in PPROM. Here, we further investigated the relationship of lncRNAs, which are differentially expressed in spontaneous PTB (sPTB) and PPROM placentas and are found to overlap a coding locus, with the differential expression of transcribed mRNAs at the same locus. Ten lncRNAs (five up-regulated and five down-regulated) and the lncRNA-associated 10 mRNAs (six up- and four down-regulated), which were identified by microarray in comparing PPROM vs. sPTB, were then validated by real-time quantitative PCR. A total of 62 (38 up- and 24 down-regulated) and 1,923 (790 up- and 1,133 down-regulated) lncRNAs were identified from placentas of premature labor (sPTB + PPROM), as compared to those from full-term labor (FTB + PROM) and from premature rupture of membranes (PPROM + PROM), as compared to those from non-rupture of membranes (sPTB + FTB), respectively. We found that a correlation existed between differentially expressed lncRNAs and their associated mRNAs, which could be grouped into four categories based on the gene strand (sense or antisense) of lncRNA and its paired transcript. These findings suggest that lncRNA regulates mRNA transcription through differential mechanisms. Differential expression of the transcripts PPP2R5C, STAM, TACC2, EML4, PAM, PDE4B, STAM, PPP2R5C, PDE4B, and EGFR indicated a co-expression among these mRNAs, which are involved in the ubiquitine-proteasome system (UPS), in addition to signaling transduction and beta adrenergic signaling, suggesting that imbalanced regulation of UPS may present an additional mechanism underlying the premature rupture of membrane in PPROM. Differentially expressed lncRNAs that were identified from the human placentas of sPTB and PPROM may regulate their associated mRNAs through differential mechanisms and connect the ubiquitin-proteasome system with infection-inflammation pathways. Although the detailed mechanisms by which lncRNAs regulate their associated mRNAs in sPTB and PPROM are yet to be clarified, our findings open a new approach to explore the pathogenesis of sPTB and PPROM.

Potential of DosR and Rpf antigens from Mycobacterium tuberculosis to discriminate between latent and active tuberculosis in a tuberculosis endemic population of Medellin Colombia.

PubMed

Arroyo, Leonar; Marín, Diana; Franken, Kees L M C; Ottenhoff, Tom H M; Barrera, Luis F

2018-01-08

Tuberculosis (TB) remains one of the most deadly infectious diseases. One-third to one-fourth of the human population is estimated to be infected with Mycobacterium tuberculosis (Mtb) without showing clinical symptoms, a condition called latent TB infection (LTBI). Diagnosis of Mtb infection is based on the immune response to a mixture of mycobacterial antigens (PPD) or to Mtb specific ESAT-6/CFP10 antigens (IGRA), highly expressed during the initial phase of infection. However, the immune response to PPD and IGRA antigens has a low power to discriminate between LTBI and PTB. The T-cell response to a group of so-called latency (DosR-regulon-encoded) and Resuscitation Promoting (Rpf) antigens of Mtb has been proved to be significantly higher in LTBI compared to active TB across many populations, suggesting their potential use as biomarkers to differentiate latent from active TB. PBMCs from a group LTBI (n = 20) and pulmonary TB patients (PTB, n = 21) from an endemic community for TB of the city of Medellín, Colombia, were in vitro stimulated for 7 days with DosR- (Rv1737c, Rv2029c, and Rv2628), Rpf- (Rv0867c and Rv2389c), the recombinant fusion protein ESAT-6-CFP10 (E6-C10)-, or PPD-antigen. The induced IFNγ levels detectable in the supernatants of the antigen-stimulated cells were then used to calculate specificity and sensitivity in discriminating LTBI from PTB, using different statistical approaches. IFNγ production in response to DosR and Rpf antigens was significantly higher in LTBI compared to PTB. ROC curve analyses of IFNγ production allowed differentiation of LTBI from PTB with areas under the curve higher than 0.70. Furthermore, Multiple Correspondence Analysis (MCA) revealed that LTBI is associated with higher levels of IFNγ in response to the different antigens compared to PTB. Analysis based on decision trees showed that the IFNγ levels produced in response to Rv2029c was the leading variable that best-classified disease status. Finally, logistic regression analysis predicted that IFNγ produced by PBMCs in response to E6-C10, Rv2029c, Rv0867c (RpfA) and Rv2389c (RpfA) antigens correlates best with the probability of being latently infected. The Mtb antigens E6-C10, Rv2029c (PfkB), Rv0867c (RpfA) and Rv2389c (RpfA), may be potential candidates to discriminate LTBI from PTB.

Ureaplasma parvum genotype, combined vaginal colonisation with Candida albicans, and spontaneous preterm birth in an Australian cohort of pregnant women.

PubMed

Payne, Matthew S; Ireland, Demelza J; Watts, Rory; Nathan, Elizabeth A; Furfaro, Lucy L; Kemp, Matthew W; Keelan, Jeffrey A; Newnham, John P

2016-10-18

Detection of Ureaplasma, Mycoplasma and Candida spp. in the vagina during pregnancy has previously been associated with preterm birth (PTB). However, the prevalence of these microorganisms and the associated obstetric risks (likely to be population-specific) have not been determined in Australian women; furthermore, in the case of Ureaplasma spp., very few studies have attempted characterisation at the species level and none have examined genotype/serovar status to further refine risk assessment. In order to address these issues we sampled the vaginal fluid of 191 pregnant Australian women at three time points in pregnancy. Culture methods were used for detection of Ureaplasma spp. and Candida spp., and real-time PCR was used for speciation of U. parvum and U. urealyticum, non-albicans Candida spp., Mycoplasma hominis and Mycoplasma genitalium. High-resolution melt PCR was used to genotype U. parvum. Data on various lifestyle factors (including sex during pregnancy and smoking), antimicrobial use and pregnancy outcome were collected on all participants. Chi-square tests were used to assess the association of vaginal microorganisms with PTB. Detection of Ureaplasma spp. was higher among spontaneous PTB cases, specifically in the presence of U. parvum [77 % preterm (95 % confidence interval (CI) 50-100 %) vs. 36 % term (CI: 29-43 %), p = 0.004], but not U. urealyticum. The association with PTB strengthened when U. parvum genotype SV6 was detected (54 % preterm (CI: 22-85 %) vs. 15 % term (CI: 10-20 %), p = 0.002); this genotype was also present in 80 % (4/5) of cases of PTB <34 weeks gestation. When present with Candida albicans in the same sample, the association with PTB remained strong for both U. parvum [46 % preterm (CI: 15-78 %) vs. 13 % term (CI: 8-18 %), p = 0.005] and U. parvum genotype SV6 [39 % preterm (CI: 8-69 %) vs. 7 % term (CI: 3-11 %), p = 0.003]. With the exception of Candida glabrata, vaginal colonisation status for all organisms was stable throughout pregnancy. Smoking significantly increased the likelihood of detection of all target organisms. These data suggest that the presence of different species and serovars of Ureaplasma spp. in the vagina confers an increased risk of spontaneous PTB, findings which may be useful in risk assessment for identifying women who would benefit from antimicrobial treatment.

Exposure to the elemental carbon, organic carbon, nitrate and sulfate fractions of fine particulate matter and risk of preterm birth in New Jersey, Ohio, and Pennsylvania (2000-2005).

EPA Science Inventory

BACKGROUND: Particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5) has been consistently associated with preterm birth (PTB) to varying degrees, but roles of PM2.5 species have been less studied.OBJECTIVE:We estimated risk differences (RD) of PTB (reported per 106 pregnancies...

Integrated microRNA and mRNA network analysis of the human myometrial transcriptome in the transition from quiescence to labor.

PubMed

Ackerman, William E; Buhimschi, Irina A; Brubaker, Douglas; Maxwell, Sean; Rood, Kara M; Chance, Mark R; Jing, Hongwu; Mesiano, Sam; Buhimschi, Catalin S

2018-02-13

We conducted integrated transcriptomics network analyses of miRNA and mRNA interactions in human myometrium to identify novel molecular candidates potentially involved in human parturition. Myometrial biopsies were collected from women undergoing primary Cesarean deliveries in well-characterized clinical scenarios: 1) spontaneous term labor (TL, n = 5); 2) term non-labor (TNL, n = 5); 3) spontaneous preterm birth (PTB) with histologic chorioamnionitis (PTB-HCA, n = 5); and 4) indicated PTB non-labor (PTB-NL, n = 5). MicroRNAs and long RNAs were profiled using RNA sequencing, and miRNA-target interaction networks were mined for key discriminatory subnetworks. Forty miRNAs differed between TL and TNL myometrium while seven miRNAs differed between PTB-HCA vs. PTB-NL specimens; six of these miRNAs were cross-validated using quantitative PCR. Based on the combined sequencing data, unsupervised clustering revealed two non-overlapping cohorts that differed primarily by absence or presence of uterine quiescence, rather than gestational age or original clinical cohort. The intersection of differentially expressed miRNAs and their mRNA targets predicted 22 subnetworks with enriched representation of miR-146b-5p, miR-223-3p, and miR-150-5p among miRNAs, and of myocyte enhancer factor-2C (MEF2C) among mRNAs. Of four known MEF2 transcription factors, decreased MEF2A and MEF2C expression in women with uterine non-quiescence was observed in the transcriptome profiling data, and validated in a second cohort by quantitative PCR. Immunohistochemistry localized MEF2A and MEF2C to myometrial smooth muscle cells and confirmed decreased abundance with labor. Collectively, these results suggest that repression of MEF2 expression may represent a previously unrecognized process through which miRNAs contribute to the phenotypic switch from quiescence to labor in human myometrium. © The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The age-related patterns of preterm birth among urban African-American and non-Latina White mothers: The effect of paternal involvement.

PubMed

Hibbs, Shayna D; Rankin, Kristin M; DeSisto, Carla; Collins, James W

2018-05-30

Few studies have examined contributions of paternal factors to birth outcomes. Weathering is a pattern of increasing rates of adverse birth outcome with increasing maternal age. This study evaluates for an association between paternal involvement and weathering in the context of preterm birth (PTB, <37 weeks) among non-Hispanic African-American and non-Hispanic White women with and without lifelong exposure to neighborhood poverty. Using the Illinois transgenerational dataset with appended US census income information of infants (1989-1991) and their mothers (1956-1976), we compared infants of women by degree of paternal involvement: married, unmarried with father named on birth certificate, and unnamed father. Data were stratified by maternal residence in higher or lower income neighborhoods at both the time of mothers' birth and infants' birth, estimating maternal lifelong economic context. We computed race-specific PTB rates according to maternal age, lifelong neighborhood income, and paternal involvement. We calculated Mantel-Haenszel chi-square tests of linear trend from contingency tables to evaluate weathering. Among African-Americans (n = 39,991) with unnamed fathers and lifelong residence in lower income neighborhoods, PTB rate was lowest among teens at 18.8%, compared to 21.5% for 30-35 year-old mothers (p for linear trend <0.05). Among African-Americans with unnamed fathers and lifelong residence in higher income neighborhoods, PTB rate among teens was 16%, compared to 25% for 30-35 year-old mothers (p = 0.21). Among married African-Americans with lifelong residence in lower income neighborhoods, PTB rate among teens was 16.4%, compared to 12.5% for 30-35 year-old mothers (p = 0.79). Among married African-Americans with lifelong residence in higher income neighborhoods, PTB rate among teens was 20%, compared to 11.4% for 30-35 year-old mothers (p = 0.40). White mothers (n = 31,981) did not demonstrate weathering, regardless of paternal involvement and neighborhood poverty. We conclude that weathering was not seen among married African-Americans, independent of neighborhood income, suggesting a potentially protective mechanism associated with paternal involvement. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identifying Stable Reference Genes for qRT-PCR Normalisation in Gene Expression Studies of Narrow-Leafed Lupin (Lupinus angustifolius L.).

PubMed

Taylor, Candy M; Jost, Ricarda; Erskine, William; Nelson, Matthew N

2016-01-01

Quantitative Reverse Transcription PCR (qRT-PCR) is currently one of the most popular, high-throughput and sensitive technologies available for quantifying gene expression. Its accurate application depends heavily upon normalisation of gene-of-interest data with reference genes that are uniformly expressed under experimental conditions. The aim of this study was to provide the first validation of reference genes for Lupinus angustifolius (narrow-leafed lupin, a significant grain legume crop) using a selection of seven genes previously trialed as reference genes for the model legume, Medicago truncatula. In a preliminary evaluation, the seven candidate reference genes were assessed on the basis of primer specificity for their respective targeted region, PCR amplification efficiency, and ability to discriminate between cDNA and gDNA. Following this assessment, expression of the three most promising candidates [Ubiquitin C (UBC), Helicase (HEL), and Polypyrimidine tract-binding protein (PTB)] was evaluated using the NormFinder and RefFinder statistical algorithms in two narrow-leafed lupin lines, both with and without vernalisation treatment, and across seven organ types (cotyledons, stem, leaves, shoot apical meristem, flowers, pods and roots) encompassing three developmental stages. UBC was consistently identified as the most stable candidate and has sufficiently uniform expression that it may be used as a sole reference gene under the experimental conditions tested here. However, as organ type and developmental stage were associated with greater variability in relative expression, it is recommended using UBC and HEL as a pair to achieve optimal normalisation. These results highlight the importance of rigorously assessing candidate reference genes for each species across a diverse range of organs and developmental stages. With emerging technologies, such as RNAseq, and the completion of valuable transcriptome data sets, it is possible that other potentially more suitable reference genes will be identified for this species in future.

Identifying Stable Reference Genes for qRT-PCR Normalisation in Gene Expression Studies of Narrow-Leafed Lupin (Lupinus angustifolius L.)

PubMed Central

Erskine, William; Nelson, Matthew N.

2016-01-01

Quantitative Reverse Transcription PCR (qRT-PCR) is currently one of the most popular, high-throughput and sensitive technologies available for quantifying gene expression. Its accurate application depends heavily upon normalisation of gene-of-interest data with reference genes that are uniformly expressed under experimental conditions. The aim of this study was to provide the first validation of reference genes for Lupinus angustifolius (narrow-leafed lupin, a significant grain legume crop) using a selection of seven genes previously trialed as reference genes for the model legume, Medicago truncatula. In a preliminary evaluation, the seven candidate reference genes were assessed on the basis of primer specificity for their respective targeted region, PCR amplification efficiency, and ability to discriminate between cDNA and gDNA. Following this assessment, expression of the three most promising candidates [Ubiquitin C (UBC), Helicase (HEL), and Polypyrimidine tract-binding protein (PTB)] was evaluated using the NormFinder and RefFinder statistical algorithms in two narrow-leafed lupin lines, both with and without vernalisation treatment, and across seven organ types (cotyledons, stem, leaves, shoot apical meristem, flowers, pods and roots) encompassing three developmental stages. UBC was consistently identified as the most stable candidate and has sufficiently uniform expression that it may be used as a sole reference gene under the experimental conditions tested here. However, as organ type and developmental stage were associated with greater variability in relative expression, it is recommended using UBC and HEL as a pair to achieve optimal normalisation. These results highlight the importance of rigorously assessing candidate reference genes for each species across a diverse range of organs and developmental stages. With emerging technologies, such as RNAseq, and the completion of valuable transcriptome data sets, it is possible that other potentially more suitable reference genes will be identified for this species in future. PMID:26872362

VP24 Is a Chitin-Binding Protein Involved in White Spot Syndrome Virus Infection

PubMed Central

Li, Zaipeng; Han, Yali; Xu, Limei

2015-01-01

ABSTRACT Oral ingestion is the major route of infection for the white spot syndrome virus (WSSV). However, the mechanism by which virus particles in the digestive tract invade host cells is unknown. In the present study, we demonstrate that WSSV virions can bind to chitin through one of the major envelope proteins (VP24). Mutagenesis analysis indicated that amino acids (aa) 186 to 200 in the C terminus of VP24 were required for chitin binding. Moreover, the P-VP24186–200 peptide derived from the VP24 chitin binding region significantly inhibited the VP24-chitin interaction and the WSSV-chitin interaction, implying that VP24 participates in WSSV binding to chitin. Oral inoculation experiments showed that P-VP24186–200 treatment reduced the number of virus particles remaining in the digestive tract during the early stage of infection and greatly hindered WSSV proliferation in shrimp. These data indicate that binding of WSSV to chitin through the viral envelope protein VP24 is essential for WSSV per os infection and provide new ideas for preventing WSSV infection in shrimp farms. IMPORTANCE In this study, we show that WSSV can bind to chitin through the envelope protein VP24. The chitin-binding domain of VP24 maps to amino acids 186 to 200 in the C terminus. Binding of WSSV to chitin through the viral envelope protein VP24 is essential for WSSV per os infection. These findings not only extend our knowledge of WSSV infection but also provide new insights into strategies to prevent WSSV infection in shrimp farms. PMID:26512091

The SAM domains of Anks family proteins are critically involved in modulating the degradation of EphA receptors.

PubMed

Kim, Jieun; Lee, Haeryung; Kim, Yujin; Yoo, Sooyeon; Park, Eunjeong; Park, Soochul

2010-04-01

We recently reported that the phosphotyrosine-binding (PTB) domain of Anks family proteins binds to EphA8, thereby positively regulating EphA8-mediated signaling pathways. In the current study, we identified a potential role for the SAM domains of Anks family proteins in EphA signaling. We found that SAM domains of Anks family proteins directly bind to ubiquitin, suggesting that Anks proteins regulate the degradation of ubiquitinated EphA receptors. Consistent with the role of Cbl ubiquitin ligases in the degradation of Eph receptors, our results revealed that the ubiquitin ligase c-Cbl induced the ubiquitination and degradation of EphA8 upon ligand binding. Ubiquitinated EphA8 also bound to the SAM domains of Odin, a member of the Anks family proteins. More importantly, the overexpression of wild-type Odin protected EphA8 and EphA2 from undergoing degradation following ligand stimulation and promoted EphA-mediated inhibition of cell migration. In contrast, a SAM domain deletion mutant of Odin strongly impaired the function of endogenous Odin, suggesting that the mutant functions in a dominant-negative manner. An analysis of Odin-deficient primary embryonic fibroblasts indicated that Odin levels play a critical role in regulating the stability of EphA2 in response to ligand stimulation. Taken together, our studies suggest that the SAM domains of Anks family proteins play a pivotal role in enhancing the stability of EphA receptors by modulating the ubiquitination process.

Contribution of prepregnancy body mass index and gestational weight gain to adverse neonatal outcomes: population attributable fractions for Canada.

PubMed

Dzakpasu, Susie; Fahey, John; Kirby, Russell S; Tough, Suzanne C; Chalmers, Beverley; Heaman, Maureen I; Bartholomew, Sharon; Biringer, Anne; Darling, Elizabeth K; Lee, Lily S; McDonald, Sarah D

2015-02-05

Low or high prepregnancy body mass index (BMI) and inadequate or excess gestational weight gain (GWG) are associated with adverse neonatal outcomes. This study estimates the contribution of these risk factors to preterm births (PTBs), small-for-gestational age (SGA) and large-for-gestational age (LGA) births in Canada compared to the contribution of prenatal smoking, a recognized perinatal risk factor. We analyzed data from the Canadian Maternity Experiences Survey. A sample of 5,930 women who had a singleton live birth in 2005-2006 was weighted to a nationally representative population of 71,200 women. From adjusted odds ratios, we calculated population attributable fractions to estimate the contribution of BMI, GWG and prenatal smoking to PTB, SGA and LGA infants overall and across four obstetric groups. Overall, 6% of women were underweight (<18.5 kg/m(2)) and 34.4% were overweight or obese (≥25.0 kg/m(2)). More than half (59.4%) gained above the recommended weight for their BMI, 18.6% gained less than the recommended weight and 10.4% smoked prenatally. Excess GWG contributed more to adverse outcomes than BMI, contributing to 18.2% of PTB and 15.9% of LGA. Although the distribution of BMI and GWG was similar across obstetric groups, their impact was greater among primigravid women and multigravid women without a previous PTB or pregnancy loss. The contributions of BMI and GWG to PTB and SGA exceeded that of prenatal smoking. Maternal weight, and GWG in particular, contributes significantly to the occurrence of adverse neonatal outcomes in Canada. Indeed, this contribution exceeds that of prenatal smoking for PTB and SGA, highlighting its public health importance.

Ethno-Specific Risk Factors for Adverse Pregnancy Outcomes: Findings from the Born in Bradford Cohort Study.

PubMed

Stacey, Tomasina; Prady, Stephanie; Haith-Cooper, Melanie; Downe, Soo; Simpson, Nigel; Pickett, Kate

2016-07-01

Objectives Preterm birth (PTB) and small for gestational age (SGA) are major causes of perinatal mortality and morbidity. Previous studies indicated a range of risk factors associated with these poor outcomes, including maternal psychosocial and economic wellbeing. This paper will explore a range of psycho-social and economic factors in an ethnically diverse population. Methods The UK's Born in Bradford cohort study recruited pregnant women attending a routine antenatal appointment at 26-28 weeks' gestation at the Bradford Royal Infirmary (2007-2010). This analysis includes 9680 women with singleton live births who completed the baseline questionnaire. Data regarding maternal socio-demographic and mental health were recorded. Outcome data were collected prospectively, and analysed using multivariate regression models. The primary outcomes measured were: PTB (<37 weeks' gestation) and SGA (<10th customised centile). Results After adjustment for socio-demographic and medical factors, financial strain was associated with a 45 % increase in PTB (OR 1.45: 95 % CI 1.06-1.98). Contrary to expectation, maternal distress in Pakistani women was negatively associated with SGA (OR 0.65: CI 0.48-0.88). Obesity in White British women was protective for PTB (OR 0.67: CI 0.45-0.98). Previously recognized risk factors, such as smoking in pregnancy and hypertension, were confirmed. Conclusions This study confirms known risk factors for PTB and SGA, along with a new variable of interest, financial strain. It also reveals a difference in the risk factors between ethnicities. In order to develop appropriate targeted preventative strategies to improve perinatal outcome in disadvantaged groups, a greater understanding of ethno-specific risk factors is required.

Helicobacter pylori colonization and pregnancies complicated by preeclampsia, spontaneous prematurity, and small for gestational age birth.

PubMed

den Hollander, Wouter J; Schalekamp-Timmermans, Sarah; Holster, I Lisanne; Jaddoe, Vincent W; Hofman, Albert; Moll, Henriëtte A; Perez-Perez, Guillermo I; Blaser, Martin J; Steegers, Eric A P; Kuipers, Ernst J

2017-04-01

Preeclampsia (PE), small for gestational age (SGA), and spontaneous preterm birth (PTB) each may be complications of impaired placental function in pregnancy. Although their exact pathogenesis is still unknown, certain infectious agents seem to play a role. Helicobacter pylori (H. pylori) colonization has been associated with increased risk for PE. Our aim was to assess the association between H. pylori colonization and PE, SGA, and PTB. We measured IgG anti-H. pylori and CagA antibodies in serum of pregnant women (median 20.5 weeks, range 16.5-29.4) who participated in a population-based prospective cohort study. Delivery and medical records were assessed. Information on demographics, education, and maternal risk factors was collected by questionnaire. We used multivariate logistic regression analyses to assess associations between H. pylori colonization and PE, SGA, and PTB. In total, 6348 pregnant women were assessed. H. pylori positivity was found in 2915 (46%) women, of whom 1023 (35%) also were CagA-positive. Pregnancy was complicated by PE, SGA, or PTB in 927 (15%) women. H. pylori colonization was associated with PE (aOR 1.51; 95%CI 1.03-2.25). Differentiation according to CagA status revealed the same risk. H. pylori was positively related with SGA, mainly explained by CagA-positive strains (aOR 1.34; 1.04-1.71). No association was observed between H. pylori and PTB. Our data suggest that H. pylori colonization may be a risk factor for PE and SGA. If these associations are confirmed by future studies and shown to be causal, H. pylori eradication may reduce related perinatal morbidity and mortality. © 2016 John Wiley & Sons Ltd.

A high resolution computer tomography scoring system to predict culture-positive pulmonary tuberculosis in the emergency department.

PubMed

Yeh, Jun-Jun; Neoh, Choo-Aun; Chen, Cheng-Ren; Chou, Christine Yi-Ting; Wu, Ming-Ting

2014-01-01

This study evaluated the use of high-resolution computed tomography (HRCT) to predict the presence of culture-positive pulmonary tuberculosis (PTB) in adult patients with pulmonary lesions in the emergency department (ED). The study included a derivation phase and validation phase with a total of 8,245 patients with pulmonary disease. There were 132 patients with culture-positive PTB in the derivation phase and 147 patients with culture-positive PTB in the validation phase. Imaging evaluation of pulmonary lesions included morphology and segmental distribution. The post-test probability ratios between both phases in three prevalence areas were analyzed. In the derivation phase, a multivariate analysis model identified cavitation, consolidation, and clusters/nodules in right or left upper lobe (except anterior segment) and consolidation of the superior segment of the right or left lower lobe as independent positive factors for culture-positive PTB, while consolidation of the right or left lower lobe (except superior segment) were independent negative factors. An ideal cutoff point based on the receiver operating characteristic (ROC) curve analysis was obtained at a score of 1. The sensitivity, specificity, positivity predictive value, and negative predictive value from derivation phase were 98.5% (130/132), 99.7% (3997/4008), 92.2% (130/141), and 99.9% (3997/3999). Based on the predicted positive likelihood ratio value of 328.33 in derivation phase, the post-test probability was observed to be 91.5% in the derivation phase, 92.5% in the validation phase, 94.5% in a high TB prevalence area, 91.0% in a moderate prevalence area, and 76.8% in moderate-to-low prevalence area. Our model using HRCT, which is feasible to perform in the ED, can promptly diagnose culture-positive PTB in moderate and moderate-to-low prevalence areas.

High precision time calibration of the Permian-Triassic boundary mass extinction event in a deep marine context

NASA Astrophysics Data System (ADS)

Baresel, Björn; Bucher, Hugo; Brosse, Morgane; Bagherpour, Borhan; Schaltegger, Urs

2015-04-01

To construct a revised and high resolution calibrated time scale for the Permian-Triassic boundary (PTB) we use (1) high-precision U-Pb zircon age determinations of a unique succession of volcanic ash layers interbedded with deep water fossiliferous sediments in the Nanpanjiang Basin (South China) combined with (2) accurate quantitative biochronology based on ammonoids, conodonts, radiolarians, and foraminifera and (3) tracers of marine bioproductivity (carbon isotopes) across the PTB. The unprecedented precision of the single grain chemical abrasion isotope-dilution thermal ionization mass spectrometry (CA-ID-TIMS) dating technique at sub-per mil level (radio-isotopic calibration of the PTB at the <100 ka level) now allows calibrating magmatic and biological timescales at resolution adequate for both groups of processes. Using these alignments allows (1) positioning the PTB in different depositional setting and (2) solving the age contradictions generated by the misleading use of the first occurrence (FO) of the conodont Hindeodus parvus, whose diachronous first occurrences are arbitrarily used for placing the base of the Triassic. This new age framework provides the basis for a combined calibration of chemostratigraphic records with high-resolution biochronozones of the Late Permian and Early Triassic. Here, we present new single grain U-Pb zircon data of volcanic ash layers from two deep marine sections (Dongpan and Penglaitan) revealing stratigraphic consistent dates over several volcanic ash layers bracketing the PTB. These analyses define weighted mean 206Pb/238U ages of 251.956±0.033 Ma (Dongpan) and 252.062±0.043 Ma (Penglaitan) for the last Permian ash bed. By calibration with detailed litho- and biostratigraphy new U-Pb ages of 251.953±0.038 Ma (Dongpan) and 251.907±0.033 Ma (Penglaitan) are established for the onset of the Triassic.

Risk factors for the treatment outcome of retreated pulmonary tuberculosis patients in China: an optimized prediction model.

PubMed

Wang, X-M; Yin, S-H; Du, J; Du, M-L; Wang, P-Y; Wu, J; Horbinski, C M; Wu, M-J; Zheng, H-Q; Xu, X-Q; Shu, W; Zhang, Y-J

2017-07-01

Retreatment of tuberculosis (TB) often fails in China, yet the risk factors associated with the failure remain unclear. To identify risk factors for the treatment failure of retreated pulmonary tuberculosis (PTB) patients, we analyzed the data of 395 retreated PTB patients who received retreatment between July 2009 and July 2011 in China. PTB patients were categorized into 'success' and 'failure' groups by their treatment outcome. Univariable and multivariable logistic regression were used to evaluate the association between treatment outcome and socio-demographic as well as clinical factors. We also created an optimized risk score model to evaluate the predictive values of these risk factors on treatment failure. Of 395 patients, 99 (25·1%) were diagnosed as retreatment failure. Our results showed that risk factors associated with treatment failure included drug resistance, low education level, low body mass index (6 months), standard treatment regimen, retreatment type, positive culture result after 2 months of treatment, and the place where the first medicine was taken. An Optimized Framingham risk model was then used to calculate the risk scores of these factors. Place where first medicine was taken (temporary living places) received a score of 6, which was highest among all the factors. The predicted probability of treatment failure increases as risk score increases. Ten out of 359 patients had a risk score >9, which corresponded to an estimated probability of treatment failure >70%. In conclusion, we have identified multiple clinical and socio-demographic factors that are associated with treatment failure of retreated PTB patients. We also created an optimized risk score model that was effective in predicting the retreatment failure. These results provide novel insights for the prognosis and improvement of treatment for retreated PTB patients.

iNKT-CELL ACTIVATION INDUCES LATE PRETERM BIRTH THAT IS ATTENUATED BY ROSIGLITAZONE1

PubMed Central

St Louis, Derek; Romero, Roberto; Plazyo, Olesya; Arenas-Hernandez, Marcia; Panaitescu, Bogdan; Xu, Yi; Milovic, Tatjana; Xu, Zhonghui; Bhatti, Gaurav; Qing-Sheng, Mi; Drewlo, Sascha; Tarca, Adi L.; Hassan, Sonia S.; Gomez-Lopez, Nardhy

2015-01-01

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality; however, its non-infection-related mechanisms are poorly understood. Herein, we show that the expansion of activated CD1d-restricted invariant NKT (iNKT) cells in the third trimester by administration of α-galactosylceramide (α-GalCer) induces late PTB and neonatal mortality. In vivo imaging revealed that fetuses from mice that underwent α-GalCer-induced late PTB had bradycardia and died shortly after delivery. Yet, administration of α-GalCer in the second trimester did not cause pregnancy loss. PPARγ activation, through rosiglitazone treatment, reduced the rate of α-GalCer-induced late PTB and improved neonatal survival. Administration of α-GalCer in the third trimester suppressed PPARγ activation as shown by the down-regulation of Fabp4 and Fatp4 in myometrial and decidual tissues, respectively; this suppression was rescued by rosiglitazone treatment. Administration of α-GalCer in the third trimester induced an increase in the activation of conventional CD4+ T cells in myometrial tissues and the infiltration of activated macrophages, neutrophils and mature DCs to myometrial and/or decidual tissues. All of these effects were blunted after rosiglitazone treatment. Administration of α-GalCer also up-regulated the expression of inflammatory genes at the maternal-fetal interface and systemically, and rosiglitazone treatment partially attenuated these responses. Finally, an increased infiltration of activated iNKT-like cells in human decidual tissues is associated with non-infection-related preterm labor/birth. Collectively, these results demonstrate that iNKT-cell activation in vivo leads to late PTB by initiating innate and adaptive immune responses and suggest that the PPARγ pathway has potential as a target for prevention of this syndrome. PMID:26740111

Diagnostic Delay among Adults with Pulmonary Tuberculosis in a High Gross Domestic Product Per Capita Country: Reasons and Magnitude of the Problem.

PubMed

Ibrahim, Wanis H; Alousi, Faraj H; Al-Khal, Abdulatif; Bener, Abdulbari; AlSalman, Ahmed; Aamer, Aaiza; Khaled, Ahmed; Raza, Tasleem

2016-01-01

To determine the mean and median delays in pulmonary tuberculosis (PTB) diagnosis among adults in one of the world's highest gross domestic product per capita countries and identify patient and health system-related reasons for these delays. This is a cross-sectional, face-to-face, prospective study of 100 subjects with confirmed PTB, conducted at main tuberculosis (TB) admitting facilities in Qatar. The mean and median diagnostic delays were measured. The Chi-square test with two-sided P < 0.05 was considered to determine the association between factors and diagnostic delay. The mean and median total diagnostic delays of PTB were 53 (95% confidence interval [CI] 42.61-63.59) and 30 (interquartile range; Q1-Q3, 15-60) days, respectively. The mean patient factor delay was 45.7 (95% CI 28.1-63.4) days, and the median was 30 (interquartile range; Q1-Q3, 15-60) days. The mean health system factor delay was 46.3 (95% CI 35.46-57.06) days, and the median was 30 (interquartile range; Q1-Q3, 18-60) days. The most common cause of patient factor delay was neglect of TB symptoms by patients (in 39% of cases), and for health-care system factor delay was a failure (mostly at general and private care levels) to suspect PTB by doctors (in 57% of cases). There were no significant associations between the presence of language barrier, patient occupation or nationality, and diagnostic delay. Despite a favorable comparison to other countries, there is a substantial delay in the diagnosis of PTB in Qatar. Relevant actions including health education on TB are required to minimize this delay.

Efficacy of T Regulatory Cells, Th17 Cells and the Associated Markers in Monitoring Tuberculosis Treatment Response

PubMed Central

Agrawal, Sonali; Parkash, Om; Palaniappan, Alangudi Natarajan; Bhatia, Ashok Kumar; Kumar, Santosh; Chauhan, Devendra Singh; Madhan Kumar, M.

2018-01-01

Treatment monitoring is an essential aspect for tuberculosis (TB) disease management. Sputum smear microscopy is the only available tool for monitoring, but it suffers from demerits. Therefore, we sought to evaluate markers and cellular subsets of T regulatory (Treg) cells and T helper (Th) 17 cells in pulmonary TB patients (PTB) for TB treatment monitoring. Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro (with purified protein derivative (PPD)) overnight which was followed by a polychromatic flow cytometry approach to study Treg and Th17 markers and cellular subsets in PTB (n = 12) undergoing antituberculous treatment (ATT). The baseline levels of these markers and cellular subsets were evaluated in normal healthy subjects (NHS). We observed a significant decrease in the expression of CD25 (p<0.01) marker and percentage of T-cell subsets like CD4+CD25+ (p<0.001) and CD4+CD25+CD39+ (p<0.05) at the end of intensive phase (IP) as well as in the continuation phase (CP) of ATT. A decrease in CD25 marker expression and percentage of CD4+CD25+ T cell subset showed a positive correlation to sputum conversion both in high and low sputum positive PTB. In eight PTB with cavitary lesions, only CD4+CD25+FoxP3 Treg subset manifested a significant decrease at the end of CP. Thus, results of this study show that CD25 marker and CD4+CD25+ T cells can serve as better markers for monitoring TB treatment efficacy. The Treg subset CD4+CD25+FoxP3 may be useful for prediction of favorable response in PTB with extensive lung lesions. However, these findings have to be evaluated in a larger patient cohort. PMID:29472922

Accumulation of FOXP3+T-cells in the tumor microenvironment is associated with an epithelial-mesenchymal-transition-type tumor budding phenotype and is an independent prognostic factor in surgically resected pancreatic ductal adenocarcinoma

PubMed Central

Wartenberg, Martin; Zlobec, Inti; Perren, Aurel; Koelzer, Viktor Hendrik; Gloor, Beat; Lugli, Alessandro; Eva, Karamitopoulou

2015-01-01

Here we explore the role of the interplay between host immune response and epithelial-mesenchymal-transition (EMT)-Type tumor-budding on the outcome of pancreatic adenocarcinoma (PDAC). CD4+, CD8+, and FOXP3+T-cells as well as iNOS+ (M1) and CD163+-macrophages (M2) were assessed on multipunch tissue-microarrays containing 120 well-characterized PDACs, precursor lesions (PanINs) and corresponding normal tissue. Counts were normalized for the percentage of tumor/spot and associated with the clinico-pathological features, including peritumoral (PTB) and intratumoral (ITB) EMT-Type tumor-budding and outcome. Increased FOXP3+T-cell-counts and CD163-macrophages and decreased CD8+T-cell-counts were observed in PDACs compared with normal tissues and PanINs (p < 0.0001). Increased peritumoral FOXP3+T-cell-counts correlated significantly with venous invasion, distant metastasis, R1-status, high-grade ITB, PTB and independently with reduced survival. Increased intratumoral FOXP3+T-cells correlated with lymphatic invasion, N1-stage, PTB and marginally with adverse outcome. High peritumoral CD163-counts correlated with venous invasion, PTB and ITB. High intratumoral CD163-counts correlated with higher T-stage and PTB. PDAC-microenvironment displays a tumor-favoring immune-cell composition especially in the immediate environment of the tumor-buds that promotes further growth and indicates a close interaction of the immune response with the EMT-process. Increased peritumoral FOXP3+T-cell density is identified as an independent adverse prognostic factor in PDAC. Patients with phenotypically aggressive PDACs may profit from targeted immunotherapy against FOXP3. PMID:25669968

Cost-benefit study of consumer product take-back programs using IBM's WIT reverse logistics optimization tool

NASA Astrophysics Data System (ADS)

Veerakamolmal, Pitipong; Lee, Yung-Joon; Fasano, J. P.; Hale, Rhea; Jacques, Mary

2002-02-01

In recent years, there has been increased focus by regulators, manufacturers, and consumers on the issue of product end of life management for electronics. This paper presents an overview of a conceptual study designed to examine the costs and benefits of several different Product Take Back (PTB) scenarios for used electronics equipment. The study utilized a reverse logistics supply chain model to examine the effects of several different factors in PTB programs. The model was done using the IBM supply chain optimization tool known as WIT (Watson Implosion Technology). Using the WIT tool, we were able to determine a theoretical optimal cost scenario for PTB programs. The study was designed to assist IBM internally in determining theoretical optimal Product Take Back program models and determining potential incentives for increasing participation rates.

Electronic Transitions of Palladium Monoboride and Platinum Monoboride

NASA Astrophysics Data System (ADS)

Ng, Y. W.; Pang, H. F.; Wong, Y. S.; Qian, Yue; Cheung, A. S.-C.

2012-06-01

Electronic transition spectrum of palladium monoboride (PdB) and platinum (PtB) monoboride have been studied using the technique of laser-ablation/reaction free jet expansion and laser induced fluorescence spectroscopy. The metal monoborides were produced by reacting laser ablated metal atoms and diborane ((B_2H_6) seeded in argon. Five and six vibrational bands were observed respectively for the PdB and PtB molecules. Preliminary analysis of the rotationally resolved structure showed that both molecules have X2 Σ+ ground state. Least-squares fit of the measured line positions yielded molecular constants for the electronic states involved. Molecular and electronic structures of PdB and PtB are discussed using a molecular orbital energy level diagram. Financial support from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKU 701008P) is gratefully acknowledged.

New measurements of W-values for protons and alpha particles.

PubMed

Giesen, U; Beck, J

2014-10-01

The increasing importance of ion beams in cancer therapy and the lack of experimental data for W-values for protons and heavy ions in air require new measurements. A new experimental set-up was developed at PTB and consistent measurements of W-values in argon, nitrogen and air for protons and alpha particles with energies from 0.7 to 3.5 MeV u(-1) at PTB, and for carbon ions between 3.6 and 7.0 MeV u(-1) at GSI were carried out. This publication concentrates on the measurements with protons and alpha particles at PTB. The experimental methods and the determination of corrections for recombination effects, beam-induced background radiation and additional effects are presented. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A linear lattice model for polyglutamine in CAG-expansion diseases.

PubMed

Bennett, Melanie J; Huey-Tubman, Kathryn E; Herr, Andrew B; West, Anthony P; Ross, Scott A; Bjorkman, Pamela J

2002-09-03

Huntington's disease and several other neurological diseases are caused by expanded polyglutamine [poly(Gln)] tracts in different proteins. Mechanisms for expanded (>36 Gln residues) poly(Gln) toxicity include the formation of aggregates that recruit and sequester essential cellular proteins [Preisinger, E., Jordan, B. M., Kazantsev, A. & Housman, D. (1999) Phil. Trans. R. Soc. London B 354, 1029-1034; Chen, S., Berthelier, V., Yang, W. & Wetzel, R. (2001) J. Mol. Biol. 311, 173-182] and functional alterations, such as improper interactions with other proteins [Cummings, C. J. & Zoghbi, H. Y. (2000) Hum. Mol. Genet. 9, 909-916]. Expansion above the "pathologic threshold" ( approximately 36 Gln) has been proposed to induce a conformational transition in poly(Gln) tracts, which has been suggested as a target for therapeutic intervention. Here we show that structural analyses of soluble huntingtin exon 1 fusion proteins with 16 to 46 glutamine residues reveal extended structures with random coil characteristics and no evidence for a global conformational change above 36 glutamines. An antibody (MW1) Fab fragment, which recognizes full-length huntingtin in mouse brain sections, binds specifically to exon 1 constructs containing normal and expanded poly(Gln) tracts, with affinity and stoichiometry that increase with poly(Gln) length. These data support a "linear lattice" model for poly(Gln), in which expanded poly(Gln) tracts have an increased number of ligand-binding sites as compared with normal poly(Gln). The linear lattice model provides a rationale for pathogenicity of expanded poly(Gln) tracts and a structural framework for drug design.

Triple Helical Recognition of Pyrimidine Inversions in Polypurine Tracts of RNA by Nucleobase-modified PNA

PubMed Central

Gupta, Pankaj; Zengeya, Thomas; Rozners, Eriks

2013-01-01

Peptide nucleic acids containing 2-pyrimidinone (P) and 3-oxo-2,3-dihydropyridazine (E) heterocycles recognized C-G and U-A inversions in a polypurine tract of double helical RNA with high affinity and sequence selectivity at pH 6.25. E-modified PNA bound strongly to bacterial A-site RNA, while no binding was observed to the human A-site RNA. PMID:21909545

Conformational and thermodynamic hallmarks of DNA operator site specificity in the copper sensitive operon repressor from Streptomyces lividans

PubMed Central

Tan, Benedict G.; Vijgenboom, Erik; Worrall, Jonathan A. R.

2014-01-01

Metal ion homeostasis in bacteria relies on metalloregulatory proteins to upregulate metal resistance genes and enable the organism to preclude metal toxicity. The copper sensitive operon repressor (CsoR) family is widely distributed in bacteria and controls the expression of copper efflux systems. CsoR operator sites consist of G-tract containing pseudopalindromes of which the mechanism of operator binding is poorly understood. Here, we use a structurally characterized CsoR from Streptomyces lividans (CsoRSl) together with three specific operator targets to reveal the salient features pertaining to the mechanism of DNA binding. We reveal that CsoRSl binds to its operator site through a 2-fold axis of symmetry centred on a conserved 5′-TAC/GTA-3′ inverted repeat. Operator recognition is stringently dependent not only on electropositive residues but also on a conserved polar glutamine residue. Thermodynamic and circular dichroic signatures of the CsoRSl–DNA interaction suggest selectivity towards the A-DNA-like topology of the G-tracts at the operator site. Such properties are enhanced on protein binding thus enabling the symmetrical binding of two CsoRSl tetramers. Finally, differential binding modes may exist in operator sites having more than one 5′-TAC/GTA-3′ inverted repeat with implications in vivo for a mechanism of modular control. PMID:24121681

War-gaming application for future space systems acquisition part 1: program and technical baseline war-gaming modeling and simulation approaches

NASA Astrophysics Data System (ADS)

Nguyen, Tien M.; Guillen, Andy T.

2017-05-01

This paper describes static Bayesian game models with "Pure" and "Mixed" games for the development of an optimum Program and Technical Baseline (PTB) solution for affordable acquisition of future space systems. The paper discusses System Engineering (SE) frameworks and analytical and simulation modeling approaches for developing the optimum PTB solutions from both the government and contractor perspectives.

The Balance Between Stress and Personal Capital during Pregnancy and the Relationship with Adverse Obstetric Outcomes: Findings from the 2007 Los Angeles Mommy and Baby (LAMB) Study

PubMed Central

Wakeel, Fathima; Wisk, Lauren E.; Gee, Rebekah; Chao, Shin M.; Witt, Whitney P.

2013-01-01

Purpose Stress during pregnancy is a salient risk factor for adverse obstetric outcomes. Personal capital during pregnancy, defined as internal and social resources that help women cope with or decrease their exposure to stress, may reduce the risk of poor obstetric outcomes. Methods Using data from the 2007 Los Angeles Mommy and Baby (LAMB) survey (N=3,353), we examined the relationships between the balance of stress and personal capital during pregnancy, or the Stress-to-Capital Ratio (SCR), and adverse obstetric outcomes ((i.e., pregnancy complications, preterm birth (PTB), low birthweight (LBW), and small-for-gestational-age (SGA)). Results Women with a higher SCR (i.e. greater stress relative to personal capital during pregnancy) were significantly more likely to experience at least one pregnancy complication, PTB, and lower gestational age, but not LBW or SGA. Accounting for pregnancy complications completely mediated the association between the SCR and PTB. Conclusions Our findings indicate that experiencing greater stress relative to personal capital during pregnancy is associated with an increased risk for pregnancy complications, PTB, and lower gestational age and that pregnancy complications may be a mechanism by which the SCR is related to adverse obstetric outcomes. PMID:23812738

Lung functions among patients with pulmonary tuberculosis in Dar es Salaam - a cross-sectional study.

PubMed

Manji, Mohamed; Shayo, Grace; Mamuya, Simon; Mpembeni, Rose; Jusabani, Ahmed; Mugusi, Ferdinand

2016-04-23

Approximately 40-60 % of patients remain sufferers of sequela of obstructive, restrictive or mixed patterns of lung disease despite treatment for pulmonary tuberculosis (PTB). The prevalence of these abnormalities in Tanzania remains unknown. A descriptive cross-sectional study was carried out among 501 patients with PTB who had completed at least 20 weeks of treatment. These underwent spirometry and their lung functions were classified as normal or abnormal (obstructive, restrictive or mixed). Logistic regression models were used to explore factors associated with abnormal lung functions. Abnormal lung functions were present in 371 (74 %) patients. There were 210 (42 %) patients with obstructive, 65 (13 %) patients with restrictive and 96 (19 %) patients with mixed patterns respectively. Significant factors associated with abnormal lung functions included recurrent PTB (Adj OR 2.8, CI 1.274 - 6.106), Human Immunodeficiency Virus (HIV) negative status (Adj OR 1.7, CI 1.055 - 2.583), age more than 40 years (Adj OR 1.7, CI 1.080 - 2.804) and male sex (Adj OR 1.7, CI 1.123 - 2.614). The prevalence of abnormal lung functions is high and it is associated with male sex, age older than 40 years, recurrent PTB and HIV negative status.

Interferon-gamma response to the treatment of active pulmonary and extra-pulmonary tuberculosis.

PubMed

Liang, L; Shi, R; Liu, X; Yuan, X; Zheng, S; Zhang, G; Wang, W; Wang, J; England, K; Via, L E; Cai, Y; Goldfeder, L C; Dodd, L E; Barry, C E; Chen, R Y

2017-10-01

Interferon-gamma (IFN-γ) release assays (IGRAs) are used to diagnose tuberculosis (TB) but not to measure treatment response. To measure IFN-γ response to active anti-tuberculosis treatment. Patients from the Henan Provincial Chest Hospital, Henan, China, with TB symptoms and/or signs were enrolled into this prospective, observational cohort study and followed for 6 months of treatment, with blood and sputum samples collected at 0, 2, 4, 6, 8, 16 and 24 weeks. The QuantiFERON® TB-Gold assay was run on collected blood samples. Participants received a follow-up telephone call at 24 months to determine relapse status. Of the 152 TB patients enrolled, 135 were eligible for this analysis: 118 pulmonary (PTB) and 17 extra-pulmonary TB (EPTB) patients. IFN-γ levels declined significantly over time among all patients (P = 0.002), with this decline driven by PTB patients (P = 0.001), largely during the initial 8 weeks of treatment (P = 0.019). IFN-γ levels did not change among EPTB patients over time or against baseline culture or drug resistance status. After 6 months of effective anti-tuberculosis treatment, IFN-γ levels decreased significantly in PTB patients, largely over the initial 8 weeks of treatment. IFN-γ concentrations may offer some value for monitoring anti-tuberculosis treatment response among PTB patients.

Surgical interventions for pulmonary tuberculosis in Mumbai, India: surgical outcomes and programmatic challenges.

PubMed

Shirodkar, S; Anande, L; Dalal, A; Desai, C; Corrêa, G; Das, M; Laxmeshwar, C; Mansoor, H; Remartinez, D; Trelles, M; Isaakidis, P

2016-09-01

Setting: While surgery for pulmonary tuberculosis (PTB) is considered an important adjunct for specific cases, including drug-resistant tuberculosis, operational evidence on its feasibility and effectiveness is limited. Objective: To describe surgical outcomes and programmatic challenges of providing surgery for PTB in Mumbai, India. Design: A descriptive study of routinely collected data of surgical interventions for PTB from 2010 to 2014 in two Mumbai hospitals, one public, one private. Results: Of 85 patients, 5 (6%) died and 17 (20%) had complications, with wound infection being the most frequent. Repeat operation was required in 12 (14%) patients. Most procedures were performed on an emergency basis, and eligibility was established late in the course of treatment. Median time from admission to surgery was 51 days. Drug susceptibility test (DST) patterns and final treatment outcomes were not systematically collected. Conclusion: In a high-burden setting such as Mumbai, important data on surgery for PTB were surprisingly limited in both the private and public sectors. Eligibility for surgery was established late, culture and DST were not systematically offered, the interval between admission and surgery was long and TB outcomes were not known. Systematic data collection would allow for proper evaluation of surgery as adjunctive therapy for all forms of TB under programmatic conditions.

Surgical interventions for pulmonary tuberculosis in Mumbai, India: surgical outcomes and programmatic challenges

PubMed Central

Shirodkar, S.; Anande, L.; Dalal, A.; Desai, C.; Corrêa, G.; Laxmeshwar, C.; Mansoor, H.; Remartinez, D.; Trelles, M.; Isaakidis, P.

2016-01-01

Setting: While surgery for pulmonary tuberculosis (PTB) is considered an important adjunct for specific cases, including drug-resistant tuberculosis, operational evidence on its feasibility and effectiveness is limited. Objective: To describe surgical outcomes and programmatic challenges of providing surgery for PTB in Mumbai, India. Design: A descriptive study of routinely collected data of surgical interventions for PTB from 2010 to 2014 in two Mumbai hospitals, one public, one private. Results: Of 85 patients, 5 (6%) died and 17 (20%) had complications, with wound infection being the most frequent. Repeat operation was required in 12 (14%) patients. Most procedures were performed on an emergency basis, and eligibility was established late in the course of treatment. Median time from admission to surgery was 51 days. Drug susceptibility test (DST) patterns and final treatment outcomes were not systematically collected. Conclusion: In a high-burden setting such as Mumbai, important data on surgery for PTB were surprisingly limited in both the private and public sectors. Eligibility for surgery was established late, culture and DST were not systematically offered, the interval between admission and surgery was long and TB outcomes were not known. Systematic data collection would allow for proper evaluation of surgery as adjunctive therapy for all forms of TB under programmatic conditions. PMID:27695683

COX-2 verexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Fraser M.; Reynolds, John V.; Kay, Elaine W.

2006-02-01

Purpose: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). Methods and Materials: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. Results: Good response (TRG 1 + 2), moderate response (TRG 3), and poor response (TRG 4 + 5) were seen in 21 patients (42%), 11 patientsmore » (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3 + 4) to treatment than were those with normal COX-2 expression (p = 0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p = 0.0007, chi-square test). Conclusions: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates.« less

The Poor Survival among Pulmonary Tuberculosis Patients in Chiapas, Mexico: The Case of Los Altos Region

PubMed Central

Nájera-Ortiz, J. C.; Sánchez-Pérez, H. J.; Ochoa-Díaz-López, H.; Leal-Fernández, G.; Navarro-Giné, A.

2012-01-01

Objective. To analyse survival in patients with pulmonary tuberculosis (PTB) and factors associated with such survival. Design. Study of a cohort of patients aged over 14 years diagnosed with PTB from January 1, 1998 to July 31, 2005. During 2004–2006 a home visit was made to each patient and, during 2008-2009, they were visited again. During these visits a follow-up interview was administered; when the patient had died, a verbal autopsy was conducted with family members. Statistical analysis consisted of survival tests, Kaplan-Meier log-rank test and Cox regression. Results. Of 305 studied patients, 68 had died due to PTB by the time of the first evaluation, 237 were followed-up for a second evaluation, and 10 of them had died of PTB. According to the Cox regression, age (over 45 years) and treatment duration (under six months) were associated with a poorer survival. When treatment duration was excluded, the association between poorer survival with age persisted, whereas with having been treated via DOTS strategy, was barely significant. Conclusions. In the studied area it is necessary that patients receive a complete treatment scheme, and to give priority to patients aged over 45 years. PMID:22701170

Predicting the effect of maternal docosahexaenoic acid (DHA) supplementation to reduce early preterm birth in Australia and the United States using results of within country randomized controlled trials.

PubMed

Yelland, L N; Gajewski, B J; Colombo, J; Gibson, R A; Makrides, M; Carlson, S E

2016-09-01

The DHA to Optimize Mother Infant Outcome (DOMInO) and Kansas DHA Outcomes Study (KUDOS) were randomized controlled trials that supplemented mothers with 800 and 600mg DHA/day, respectively, or a placebo during pregnancy. DOMInO was conducted in Australia and KUDOS in the United States. Both trials found an unanticipated and statistically significant reduction in early preterm birth (ePTB; i.e., birth before 34 weeks gestation). However, in each trial, the number of ePTBs were small. We used a novel Bayesian approach to estimate statistically derived low, moderate or high risk for ePTB, and to test for differences between the DHA and placebo groups. In both trials, the model predicted DHA would significantly reduce the expected proportion of deliveries in the high risk group under the trial conditions of the parent studies. Among the next 300,000 births in Australia we estimated that 1112 ePTB (95% credible interval 51-2189) could be avoided by providing DHA. And in the USA we estimated that 106,030 ePTB (95% credible interval 6400 to 175,700) could be avoided with DHA. Copyright © 2016 Elsevier Ltd. All rights reserved.

Substance P receptor binding sites are expressed by glia in vivo after neuronal injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mantyh, P.W.; Johnson, D.J.; Boehmer, C.G.

1989-07-01

In vitro studies have demonstrated that glia can express functional receptors for a variety of neurotransmitters. To determine whether similar neurotransmitter receptors are also expressed by glia in vivo, the authors examined the glial scar in the transected optic nerve of the albino rabbit by quantitative receptor autoradiography. Receptor binding sites for radiolabeled calcitonin gene-related peptide, cholecystokinin, galanin, glutamate, somatostatin, substance P, and vasoactive intestinal peptide were examined. Specific receptor binding sites for each of these neurotransmitters were identified in the rabbit forebrain but were not detected in the normal optic nerve or tract. In the transected optic nerve andmore » tract, only receptor binding sites for substance P were expressed at detectable levels. The density of substance P receptor binding sites observed in this glial scar is among the highest observed in the rabbit forebrain. Ligand displacement and saturation experiments indicate that the substance P receptor binding site expressed by the glial scar has pharmacological characteristics similar to those of substance P receptors in the rabbit striatum, rat brain, and rat and canine gut. The present study demonstrates that glial cells in vivo express high concentrations of substance P receptor binding sites after transection of retinal ganglion cell axons. Because substance P has been shown to regulate inflammatory and immune responses in peripheral tissues, substance P may also, by analogy, be involved in regulating the glial response to injury in the central nervous system.« less

Solution Model of the Intrinsically Disordered Polyglutamine Tract-Binding Protein-1

PubMed Central

Rees, Martin; Gorba, Christian; de Chiara, Cesira; Bui, Tam T.T.; Garcia-Maya, Mitla; Drake, Alex F.; Okazawa, Hitoshi; Pastore, Annalisa; Svergun, Dmitri; Chen, Yu Wai

2012-01-01

Polyglutamine tract-binding protein-1 (PQBP-1) is a 265-residue nuclear protein that is involved in transcriptional regulation. In addition to its role in the molecular pathology of the polyglutamine expansion diseases, mutations of the protein are associated with X-linked mental retardation. PQBP-1 binds specifically to glutamine repeat sequences and proline-rich regions, and interacts with RNA polymerase II and the spliceosomal protein U5-15kD. In this work, we obtained a biophysical characterization of this protein by employing complementary structural methods. PQBP-1 is shown to be a moderately compact but largely disordered molecule with an elongated shape, having a Stokes radius of 3.7 nm and a maximum molecular dimension of 13 nm. The protein is monomeric in solution, has residual β-structure, and is in a premolten globule state that is unaffected by natural osmolytes. Using small-angle x-ray scattering data, we were able to generate a low-resolution, three-dimensional model of PQBP-1. PMID:22500761

Altered respiratory response to substance P and reduced NK1 receptor binding in the nucleus of the solitary tract of aged rats.

PubMed

Mazzone, S B; Geraghty, D P

1999-04-24

The respiratory response to microinjection of substance P (SP) into the commissural nucleus of the solitary tract (cNTS) and binding of [125I]-Bolton-Hunter SP ([125I]-BHSP) to brain stem NK1 receptors were compared in young and aged rats. Injection of SP (750 pmol) into the cNTS of young rats (2 months) increased tidal volume (VT) but had no effect on respiratory rate (f). In aged rats (19-21 months), injection of SP had no significant effect on f or VT. The NTS of aged rats displayed significantly lower specific [125I]-BHSP binding than young rats, indicating a reduction in the number in NK1 receptors. These findings show that the respiratory response to microinjection of SP into the cNTS of aged rats is severely blunted and that this phenomenon may be due to a decrease in the number of NK1 receptors in the NTS. Copyright 1999 Elsevier Science B.V.

Time Transfer Between USNO and PTB: Operation and Calibration Results

DTIC Science & Technology

2004-09-01

transfer ( TWSTFT ) is routinely executed between USNO and PTB via two links, using a connection at Ku-band and X-band. The Ku-band measurements are...desirable. Up to now, three calibration experiments were carried out with a transportable TWSTFT station provided by USNO: in June 2002, January 2003...and July 2003. Because only a few TWSTFT calibrations of civil time laboratories were performed up to now, this first “semiannual” schedule

Use of Mueller matrix polarimetry and optical coherence tomography in the characterization of cervical collagen anisotropy

NASA Astrophysics Data System (ADS)

Chue-Sang, Joseph; Bai, Yuqiang; Stoff, Susan; Gonzalez, Mariacarla; Holness, Nola; Gomes, Jefferson; Jung, Ranu; Gandjbakhche, Amir; Chernomordik, Viktor V.; Ramella-Roman, Jessica C.

2017-08-01

Preterm birth (PTB) presents a serious medical health concern throughout the world. There is a high incidence of PTB in both developed and developing countries ranging from 11% to 15%, respectively. Recent research has shown that cervical collagen orientation and distribution changes during pregnancy may be useful in predicting PTB. Polarization imaging is an effective means to measure optical anisotropy in birefringent materials, such as the cervix's extracellular matrix. Noninvasive, full-field Mueller matrix polarimetry (MMP) imaging methodologies, and optical coherence tomography (OCT) imaging were used to assess cervical collagen content and structure in nonpregnant porcine cervices. We demonstrate that the highly ordered structure of the nonpregnant porcine cervix can be observed with MMP. Furthermore, when utilized ex vivo, OCT and MMP yield very similar results with a mean error of 3.46% between the two modalities.

Use of Mueller matrix polarimetry and optical coherence tomography in the characterization of cervical collagen anisotropy.

PubMed

Chue-Sang, Joseph; Bai, Yuqiang; Stoff, Susan; Gonzalez, Mariacarla; Holness, Nola; Gomes, Jefferson; Jung, Ranu; Gandjbakhche, Amir; Chernomordik, Viktor V; Ramella-Roman, Jessica C

2017-08-01

Preterm birth (PTB) presents a serious medical health concern throughout the world. There is a high incidence of PTB in both developed and developing countries ranging from 11% to 15%, respectively. Recent research has shown that cervical collagen orientation and distribution changes during pregnancy may be useful in predicting PTB. Polarization imaging is an effective means to measure optical anisotropy in birefringent materials, such as the cervix's extracellular matrix. Noninvasive, full-field Mueller matrix polarimetry (MMP) imaging methodologies, and optical coherence tomography (OCT) imaging were used to assess cervical collagen content and structure in nonpregnant porcine cervices. We demonstrate that the highly ordered structure of the nonpregnant porcine cervix can be observed with MMP. Furthermore, when utilized ex vivo, OCT and MMP yield very similar results with a mean error of 3.46% between the two modalities. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Impact of new clock technologies on the stability and accuracy of the International Atomic Time TAI.

NASA Astrophysics Data System (ADS)

Thomas, C.

1997-05-01

The BIPM Time Section is in charge of the generation of the reference time scales TAI and UTC. Both time scales are obtained in deferred-time by combining the data front a number of atomic clocks spread worldwide. The accuracy of TAI is estimated by the departure between the duration of the TAI scale interval and the SI second as produced on the rotating geoid by primary frequency standards. It is now possible to estimate TAI accuracy through the combination of results obtained from six different primary standards: LPTF-FO1, PTB CS1, PTB CS2, PTB CS3, NIST-7, and SU MCsR 102, all corrected for the black-body radiation shift. This led to a mean departure of the TAI scale interval of +2.0×10-14s over 1995, known with a relative uncertainty of 0.5×10-14(1σ).

Trilateral Intercomparison of Photometric Units Maintained at NIST (USA), NPL (UK), and PTB (Germany)

PubMed Central

Ohno, Yoshi; Goodman, Teresa; Sauter, Georg

1999-01-01

A trilateral intercomparison of photometric units between NIST (USA), NPL (UK), and PTB (Germany) has been conducted to update the knowledge of the relationship between the photometric units disseminated in the three countries. The luminous intensity unit (cd), the luminous responsivity scale (A/lx), and the luminous flux unit (lm) maintained at each laboratory were compared by circulating transfer standard lamps and photometers. The results showed that the relative luminous intensity values, with respect to the average, measured by NIST, NPL, and PTB were 1.0014, 1.0021, and 0.9966; the relative inverse values of the luminous responsivity (corresponding to illuminance) were 1.0023, 1.0011, and 0.9965; the relative luminous flux values were 0.9994, 1.0034, and 0.9972, respectively. The results agreed within the stated uncertainties of the units maintained at the three laboratories.

PRETERM BIRTH AND FETAL GROWTH RESTRICTION IN HIV-INFECTED BRAZILIAN PREGNANT WOMEN

PubMed Central

dos REIS, Helena Lucia Barroso; ARAUJO, Karina da Silva; RIBEIRO, Lilian Paula; da ROCHA, Daniel Ribeiro; ROSATO, Drielli Petri; PASSOS, Mauro Romero Leal; de VARGAS, Paulo Roberto Merçon

2015-01-01

Introduction: Maternal HIV infection and related co-morbidities may have two outstanding consequences to fetal health: mother-to-child transmission (MTCT) and adverse perinatal outcomes. After Brazilian success in reducing MTCT, the attention must now be diverted to the potentially increased risk for preterm birth (PTB) and intrauterine fetal growth restriction (IUGR). Objective: To determine the prevalence of PTB and IUGR in low income, antiretroviral users, publicly assisted, HIV-infected women and to verify its relation to the HIV infection stage. Patients and Methods: Out of 250 deliveries from HIV-infected mothers that delivered at a tertiary public university hospital in the city of Vitória, state of Espírito Santo, Southeastern Brazil, from November 2001 to May 2012, 74 single pregnancies were selected for study, with ultrasound validated gestational age (GA) and data on birth dimensions: fetal weight (FW), birth length (BL), head and abdominal circumferences (HC, AC). The data were extracted from clinical and pathological records, and the outcomes summarized as proportions of preterm birth (PTB, < 37 weeks), low birth weight (LBW, < 2500g) and small (SGA), adequate (AGA) and large (LGA) for GA, defined as having a value below, between or beyond the ±1.28 z/GA score, the usual clinical cut-off to demarcate the 10th and 90th percentiles. Results: PTB was observed in 17.5%, LBW in 20.2% and SGA FW, BL, HC and AC in 16.2%, 19.1%, 13.8%, and 17.4% respectively. The proportions in HIV-only and AIDS cases were: PTB: 5.9 versus 27.5%, LBW: 14.7% versus 25.0%, SGA BW: 17.6% versus 15.0%, BL: 6.0% versus 30.0%, HC: 9.0% versus 17.9%, and AC: 13.3% versus 21.2%; only SGA BL attained a significant difference. Out of 15 cases of LBW, eight (53.3%) were preterm only, four (26.7%) were SGA only, and three (20.0%) were both PTB and SGA cases. A concomitant presence of, at least, two SGA dimensions in the same fetus was frequent. Conclusions: The proportions of preterm birth and low birth weight were higher than the local and Brazilian prevalence and a trend was observed for higher proportions of SGA fetal dimensions than the expected population distribution in this small casuistry of newborn from the HIV-infected, low income, antiretroviral users, and publicly assisted pregnant women. A trend for higher prevalence of PTB, LBW and SGA fetal dimensions was also observed in infants born to mothers with AIDS compared to HIV-infected mothers without AIDS. PMID:25923889

A Meta-analysis of Depression During Pregnancy and the Risk of Preterm Birth, Low Birth Weight, and Intrauterine Growth Restriction

PubMed Central

Grote, Nancy K.; Bridge, Jeffrey A.; Gavin, Amelia R.; Melville, Jennifer L.; Iyengar, Satish; Katon, Wayne J.

2011-01-01

Context Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). Objective To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. Data Sources and Study Selection We searched for English-language and non–English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB (<37 weeks’ gestation), LBW (<2500 g), or IUGR (<10th percentile for gestational age). Of 862 reviewed studies, 29 US-published and non–US-published studies met the selection criteria. Data Extraction Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. Data Synthesis Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR [95% confidence interval]=1.39 [1.19–1.61], 1.49 [1.25–1.77], and 1.45 [1.05–2.02], respectively) compared with studies that used a continuous depression measure (1.03 [1.00–1.06], 1.04 [0.99–1.09], and 1.02 [1.00–1.04], respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR=2.05; 95% confidence interval, 1.43–2.93) compared with the United States (RR=1.10; 95% confidence interval, 1.01–1.21) or European social democracies (RR=1.16; 95% confidence interval, 0.92–1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. Conclusions Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated. PMID:20921117

A chicken influenza virus recognizes fucosylated α2,3 sialoglycan receptors on the epithelial cells lining upper respiratory tracts of chickens.

PubMed

Hiono, Takahiro; Okamatsu, Masatoshi; Nishihara, Shoko; Takase-Yoden, Sayaka; Sakoda, Yoshihiro; Kida, Hiroshi

2014-05-01

Influenza viruses recognize sialoglycans as receptors. Although viruses isolated form chickens preferentially bind to sialic acid α2,3 galactose (SAα2,3Gal) glycans as do those of ducks, chickens were not experimentally infected with viruses isolated from ducks. A chicken influenza virus, A/chicken/Ibaraki/1/2005 (H5N2) (Ck/IBR) bound to fucose-branched SAα2,3Gal glycans, whereas the binding towards linear SAα2,3Gal glycans was weak. On the epithelial cells of the upper respiratory tracts of chickens, fucose-branched SAα2,3Gal glycans were detected, but not linear SAα2,3Gal glycans. The growth of Ck/IBR in MDCK-FUT cells, which were genetically prepared to express fucose-branched SAα2,3Gal glycans, was significantly higher than that in the parental MDCK cells. The present results indicate that fucose-branched SAα2,3Gal glycans existing on the epithelial cells lining the upper respiratory tracts of chickens are critical for recognition by Ck/IBR. Copyright © 2014 Elsevier Inc. All rights reserved.

Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway

PubMed Central

Ge, Zhiyun; Quek, Bao Lin; Beemon, Karen L; Hogg, J Robert

2016-01-01

The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing long 3'UTRs to perform dual roles in mRNA quality control and gene expression regulation. However, expansion of vertebrate 3'UTR functions has required a physical expansion of 3'UTR lengths, complicating the process of detecting nonsense mutations. We show that the polypyrimidine tract binding protein 1 (PTBP1) shields specific retroviral and cellular transcripts from NMD. When bound near a stop codon, PTBP1 blocks the NMD protein UPF1 from binding 3'UTRs. PTBP1 can thus mark specific stop codons as genuine, preserving both the ability of NMD to accurately detect aberrant mRNAs and the capacity of long 3'UTRs to regulate gene expression. Illustrating the wide scope of this mechanism, we use RNA-seq and transcriptome-wide analysis of PTBP1 binding sites to show that many human mRNAs are protected by PTBP1 and that PTBP1 enrichment near stop codons correlates with 3'UTR length and resistance to NMD. DOI: http://dx.doi.org/10.7554/eLife.11155.001 PMID:26744779

Antibiotics for treating bacterial vaginosis in pregnancy.

PubMed

Brocklehurst, Peter; Gordon, Adrienne; Heatley, Emer; Milan, Stephen J

2013-01-31

Bacterial vaginosis is an imbalance of the normal vaginal flora with an overgrowth of anaerobic bacteria and a lack of the normal lactobacillary flora. Women may have symptoms of a characteristic vaginal discharge but are often asymptomatic. Bacterial vaginosis during pregnancy has been associated with poor perinatal outcomes and, in particular, preterm birth (PTB). Identification and treatment may reduce the risk of PTB and its consequences. To assess the effects of antibiotic treatment of bacterial vaginosis in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2012), searched cited references from retrieved articles and reviewed abstracts, letters to the editor and editorials. Randomised trials comparing antibiotic treatment with placebo or no treatment, or comparing two or more antibiotic regimens in pregnant women with bacterial vaginosis or intermediate vaginal flora whether symptomatic or asymptomatic and detected through screening. Two review authors independently assessed trials for inclusion, trial quality and extracted data. We contacted study authors for additional information. We included 21 trials of good quality, involving 7847 women diagnosed with bacterial vaginosis or intermediate vaginal flora.Antibiotic therapy was shown to be effective at eradicating bacterial vaginosis during pregnancy (average risk ratio (RR) 0.42; 95% confidence interval (CI) 0.31 to 0.56; 10 trials, 4403 women; random-effects, T² = 0.19, I² = 91%). Antibiotic treatment also reduced the risk of late miscarriage (RR 0.20; 95% CI 0.05 to 0.76; two trials, 1270 women, fixed-effect, I² = 0%).Treatment did not reduce the risk of PTB before 37 weeks (average RR 0.88; 95% CI 0.71 to 1.09; 13 trials, 6491 women; random-effects, T² = 0.06, I² = 48%), or the risk of preterm prelabour rupture of membranes (RR 0.74; 95% CI 0.30 to 1.84; two trials, 493 women). It did increase the risk of side-effects sufficient to stop or change treatment (RR 1.66; 95% CI 1.02 to 2.68; four trials, 2323 women, fixed-effect, I² = 0%).In this updated review, treatment before 20 weeks' gestation did not reduce the risk of PTB less than 37 weeks (average RR 0.85; 95% CI 0.62 to 1.17; five trials, 4088 women; random-effects, T² = 0.06, I² = 49%).In women with a previous PTB, treatment did not affect the risk of subsequent PTB (average RR 0.78; 95% CI 0.42 to 1.48; three trials, 421 women; random-effects, T² = 0.19, I² = 72%).In women with abnormal vaginal flora (intermediate flora or bacterial vaginosis), treatment may reduce the risk of PTB before 37 weeks (RR 0.53; 95% CI 0.34 to 0.84; two trials, 894 women).One small trial of 156 women compared metronidazole and clindamycin, both oral and vaginal, with no significant differences seen for any of the pre-specified primary outcomes. Statistically significant differences were seen for the outcomes of prolongation of gestational age (days) (mean difference (MD) 1.00; 95% CI 0.26 to 1.74) and birthweight (grams) (MD 75.18; 95% CI 25.37 to 124.99) however these represent relatively small differences in the clinical setting.Oral antibiotics versus vaginal antibiotics did not reduce the risk of PTB (RR 1.09; 95% CI 0.78 to 1.52; two trials, 264 women). Oral antibiotics had some advantage over vaginal antibiotics (whether metronidazole or clindamycin) with respect to admission to neonatal unit (RR 0.63; 95% CI 0.42 to 0.92, one trial, 156 women), prolongation of gestational age (days) (MD 9.00; 95% CI 8.20 to 9.80; one trial, 156 women) and birthweight (grams) (MD 342.13; 95% CI 293.04 to 391.22; one trial, 156 women).Different frequency of dosing of antibiotics was assessed in one small trial and showed no significant difference for any outcome assessed. Antibiotic treatment can eradicate bacterial vaginosis in pregnancy. The overall risk of PTB was not significantly reduced. This review provides little evidence that screening and treating all pregnant women with bacterial vaginosis will prevent PTB and its consequences. When screening criteria were broadened to include women with abnormal flora there was a 47% reduction in preterm birth, however this is limited to two included studies.

[Evaluation of T-SPOT.TB assay in the diagnosis of pulmonary tuberculosis within different age groups].

PubMed

Pan, Liping; Jia, Hongyan; Liu, Fei; Gao, Mengqiu; Sun, Huishan; Du, Boping; Sun, Qi; Xing, Aiying; Wei, Rongrong; Zhang, Zongde

2015-12-01

To evaluate the value of T-SPOT.TB assay in the diagnosis of pulmonary tuberculosis within different age groups. We analyzed 1 518 suspected pulmonary tuberculosis (PTB) patients who were admitted to the Beijing Chest Hospital from November 2012 to February 2014 and had valid T-SPOT.TB tests before anti-tuberculosis therapy. The 599 microbiologically and/or histopathologically-confirmed PTB patients (16-89 years old, 388 males and 211 females) and 235 non-TB patients (14-85 years old, 144 males and 91 females) were enrolled for the analysis of diagnostic performance of T-SPOT.TB, while patients with uncertain diagnosis or diagnosis based on clinical impression (n=684) were excluded from the analysis. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB were analyzed according to the final diagnosis. Furthermore, the diagnostic performance of T-SPOT.TB assay in the younger patients (14-59 years old) and elderly patients (60-89 years old) were also analyzed respectively. Categorical variables were compared by Pearson's Chi-square test, while continuous variables were compared by the Mann-Whitney U-test. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB in diagnosis of PTB were 90.1% (540/599), 65.5% (154/235), 86.9% (540/621), 72.3% (154/213), 2.61, and 0.15, respectively. The sensitivity and specificity of T-SPOT.TB assay were 92.6% (375/405) and 75.6% (99/131), respectively in the younger patients, and 85.0% (165/194), 52.9% (55/104) respectively in the elderly patients. The sensitivity and specificity of T-SPOT.TB assay in the younger patients were significantly higher than those in the elderly patients (P<0.01), and the spot forming cells in the younger PTB patients were significantly higher than in the elderly PTB patients [300 (126, 666)/10(6) PBMCs vs. 258 (79, 621)/10(6) PBMCs, P=0.037]. T-SPOT.TB is a promising test in the diagnosis of younger patients (14-59 years old) with suspected PTB, but the diagnostic performance in elderly patients (60-89 years old) is relatively reduced.

Cbl Associates with Pyk2 and Src to Regulate Src Kinase Activity, αvβ3 Integrin-Mediated Signaling, Cell Adhesion, and Osteoclast Motility

PubMed Central

Sanjay, Archana; Houghton, Adam; Neff, Lynn; DiDomenico, Emilia; Bardelay, Chantal; Antoine, Evelyne; Levy, Joan; Gailit, James; Bowtell, David; Horne, William C.; Baron, Roland

2001-01-01

The signaling events downstream of integrins that regulate cell attachment and motility are only partially understood. Using osteoclasts and transfected 293 cells, we find that a molecular complex comprising Src, Pyk2, and Cbl functions to regulate cell adhesion and motility. The activation of integrin αvβ3 induces the [Ca2+]i-dependent phosphorylation of Pyk2 Y402, its association with Src SH2, Src activation, and the Src SH3-dependent recruitment and phosphorylation of c-Cbl. Furthermore, the PTB domain of Cbl is shown to bind to phosphorylated Tyr-416 in the activation loop of Src, the autophosphorylation site of Src, inhibiting Src kinase activity and integrin-mediated adhesion. Finally, we show that deletion of c Src or c-Cbl leads to a decrease in osteoclast migration. Thus, binding of αvβ3 integrin induces the formation of a Pyk2/Src/Cbl complex in which Cbl is a key regulator of Src kinase activity and of cell adhesion and migration. These findings may explain the osteopetrotic phenotype in the Src−/− mice. PMID:11149930

First-trimester antihistamine exposure and risk of spontaneous abortion or preterm birth.

PubMed

Aldridge, Tiara D; Hartmann, Katherine E; Michels, Kara A; Velez Edwards, Digna R

2014-10-01

We tested whether antihistamine exposure during early pregnancy is associated with spontaneous abortion (SAB) or preterm birth (PTB). Women were enrolled in Right from the Start (2004-2010), a prospective pregnancy cohort. Data about first-trimester antihistamine use were obtained from screening and first-trimester interviews. Self-reported outcomes included SAB and PTB and were verified by medical records. Cox proportional hazards models were used to test for an association between antihistamine use and each outcome, both performed adjusting for confounders. Among the 2685 pregnancies analyzed, 14% (n = 377) reported use of antihistamines. Among antihistamine users, 12% (n = 44) experienced SABs, and 6% (n = 21) had PTBs. Antihistamine exposure was not associated with SAB (adjusted hazard ratio [aHR] = 0.88, 95% confidence interval [CI] 0.64, 1.21) or PTB, which was modified by maternal race (aHR = 1.03, 95%CI 0.61, 1.72 among White women and aHR = 0.43, 95%CI 0.14, 1.34 among Black women). Despite the biologic plausibility that antihistamine use may influence pregnancy outcomes, we did not detect evidence of an association with SAB or PTB. These data demonstrate the utility of large prospective cohorts for evaluating drug safety in pregnancy when concerns are raised from animal models. Copyright © 2014 John Wiley & Sons, Ltd.

Increased risk of pulmonary and extra-pulmonary tuberculosis in patients with rheumatic diseases.

PubMed

Lu, M-C; Lai, C-L; Tsai, C-C; Koo, M; Lai, N-S

2015-12-01

Impaired immunity in patients with rheumatic diseases can increase the risk of pulmonary tuberculosis (PTB). However, it is less clear whether rheumatic diseases affect the risk of extra-pulmonary tuberculosis (EPTB). To investigate the risk of PTB and EPTB in patients with rheumatic diseases using a population-based database. From Taiwan's National Health Insurance Research Database, 8536 patients with tuberculosis (TB) were frequency-matched with 42,680 controls for sex, 10-year age group and index year. Subjects were retrospectively traced back for their first diagnosis of rheumatic diseases. The association between TB and rheumatic diseases was assessed using multivariate logistic regression analyses. The risk of developing PTB was significantly higher in patients with systemic lupus erythematosus (adjusted odds ratio [aOR] 4.90, P < 0.001), rheumatoid arthritis (RA) (aOR 2.00, P < 0.001) and Sjögren's syndrome (aOR 6.11, P < 0.001). In addition, the risks of developing EPTB were significantly higher in RA patients (aOR 4.67, P < 0.001), those with Sjögren's syndrome (aOR 5.94, P < 0.001), and the group comprising progressive systemic sclerosis, polymyositis or dermatomyositis (aOR 8.31, P = 0.021). Elevated risks of PTB and EPTB were associated with various rheumatic diseases. Rheumatologists should be vigilant to the possibility of TB, and particularly EPTB, in their patients.

Final report on bilateral supplementary comparison APMP.M.P-S5 in hydraulic gauge pressure from 1 MPa to 10 MPa

NASA Astrophysics Data System (ADS)

Yue, J.; Yang, Y.; Sabuga, W.

2016-01-01

This report summarizes the results of the Asia-Pacific Metrology Programme (APMP) supplementary comparison APMP.M.P-S5 for hydraulic gauge pressure in the range of 1 MPa to 10 MPa, which is a bilateral comparison carried out at the National Institute of Metrology, China (NIM) and the Physikalisch-Technische Bundesanstalt, Germany (PTB) during the period June 2014 to June 2015. NIM piloted the comparison and provided the transfer standard, which was a piston-cylinder assembly (PCA) of 1 cm2 nominal effective area built in a hydraulic pressure balance manufactured by Fluke Corporation. The laboratory standards of NIM and PTB are both hydraulic pressure balances equipped with PCAs, of which the nominal effective area is 1 cm2 for NIM and 5 cm2 for PTB. The results of the comparison successfully demonstrated that the hydraulic gauge pressure standards of NIM and PTB in the range of 1 MPa to 10 MPa are equivalent within their claimed uncertainties. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

The vitamin D hypothesis revisited: race-based disparities in birth outcomes in the United States and ultraviolet light availability.

PubMed

Thayer, Zaneta M

2014-04-15

Skin color has been proposed to contribute to race-based health disparities in the United States because of differences in ultraviolet (UV) light-induced vitamin D synthesis. The prediction of this hypothesis, herein named the UVD hypothesis, is that racial disparities in health outcomes are correlated with UV light availability. This paper investigates whether UV light availability is associated with disparities in the rates of low birth weight (LBW) and preterm birth (PTB) between whites and blacks, because these outcomes are thought to be influenced by vitamin D status and to shape disease risk in later life. Data on LBW and PTB from 2007 (n = 2,825,620 births) were compared with data on UV light exposure across the United States. Contrary to the predictions of the UVD hypothesis, LBW and PTB rate disparities were greatest in states with the highest UV light exposure. Notably, income inequality was positively and significantly related to LBW and PTB disparities, even after controlling for UV light availability. The results of this analysis demonstrate that there is a significant environmental gradient in racial disparities in birth outcomes in the United States, but other social or environmental factors associated with living in the southern United States are likely stronger contributors to disparities in birth outcomes than UV light-induced vitamin D status.

Perinatal outcomes after gestational surrogacy versus autologous IVF: analysis of national data.

PubMed

Sunkara, Sesh Kamal; Antonisamy, Belavendra; Selliah, Hepsy Y; Kamath, Mohan S

2017-12-01

Anonymized data were obtained from the Human Fertilization and Embryology Authority to determine whether gestational surrogacy influences perinatal outcomes compared with pregnancies after autologous IVF. A total of 103,160 singleton live births, including 244 after gestational surrogacy, 87,571 after autologous fresh IVF and intractyoplasmic sperm injection (ICSI) and 15,345 after autologous frozen embryo transfers were analysed. Perinatal outcomes of pretern birth (PTB), low birth weight (LBW) and high birth weight (HBW) were compared. No difference was found in the risk of PTB and LBW after gestational surrogacy compared with autologous fresh IVF-ICSI: PTB (adjusted OR 0.90, 95% CI 0.56 to 1.42), LBW (adjusted OR 0.90, 95% CI 0.57 to 1.43) and gestational surrogacy compared with autologous frozen embryo transfers: PTB (adjusted OR 0.96, 95% CI 0.58 to 1.60), LBW (adjusted OR 1.16, 95% CI 0.69 to 1.96). The incidence of HBW was significantly higher after gestational surrogacy compared with fresh IVF-ICSI (adjusted OR 1.94, 95% CI 1.38 to 2.75); no difference was found in HBW between gestational surrogacy and autologous frozen embryo transfers. The dataset is limited by lack of information on confounders, i.e. ethnicity, body mass index, underlying medical history, which could result in residual confounding. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Residential segregation and the health of African-American infants: does the effect vary by prevalence?

PubMed

Nyarko, Kwame A; Wehby, George L

2012-10-01

Segregation effects may vary between areas (e.g., counties) of low and high low birth weight (LBW; <2,500 g) and preterm birth (PTB; <37 weeks of gestation) rates due to interactions with area differences in risks and resources. We assess whether the effects of residential segregation on county-level LBW and PTB rates for African-American infants vary by the prevalence of these conditions. The study sample includes 368 counties of 100,000 or more residents and at least 50 African-American live births in 2000. Residentially segregated counties are identified alternatively by county-level dissimilarity and isolation indices. Quantile regression is used to assess how residential segregation affects the entire distributions of county-level LBW and PTB rates (i.e. by prevalence). Residential segregation increases LBW and PTB rates significantly in areas of low prevalence, but has no such effects for areas of high prevalence. As a sensitivity analysis, we use metropolitan statistical area level data and obtain similar results. Our findings suggest that residential segregation has adverse effects mainly in areas of low prevalence of LBW and preterm birth, which are expected overall to have fewer risk factors and more resources for infant health, but not in high prevalence areas, which are expected to have more risk factors and fewer resources. Residential policies aimed at area resource improvements may be more effective.

Synergistic effect of maternal obesity and periodontitis on preterm birth in women with pre-eclampsia: a prospective study.

PubMed

Lee, Hyo-Jin; Ha, Jung-Eun; Bae, Kwang-Hak

2016-08-01

The aim of this study was to investigate if pregnant women with both obesity and periodontitis are more likely to experience preterm birth (PTB) in women with pre-eclampsia (PE) than pregnant women with only obesity or only periodontitis. The study examined a total of 328 pregnant women at 21-24 weeks of gestation. Overweight and obesity was defined based on criteria proposed by the WHO Expert Consultation. Periodontal conditions were assessed by measuring periodontal clinical attachment loss. PTB was defined as delivery at <37 weeks, and PE was defined as blood pressure higher than 140/90 mmHg on two separate occasions with at least 1+ proteinuria on a random urine screen after the 20th week of pregnancy. After adjusting for other important cofactors, pregnant women with periodontitis were 5.56 times [95% confidence interval (CI) = 1.22-25.39] more likely to have PTB with PE than women without periodontitis. The association was much stronger (odds ratio = 15.94, 95% CI = 3.31-76.71) in women with both obesity and periodontitis. Our results of this study indicate that pregnant women with both pre-pregnancy obesity and periodontitis are significantly more likely to have PTB with PE than pregnant women with only periodontitis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Visualizing nanoscale phase morphology for understanding photovoltaic performance of PTB7: PC71BM solar cell

NASA Astrophysics Data System (ADS)

Supasai, Thidarat; Amornkitbamrung, Vittaya; Thanachayanont, Chanchana; Tang, I.-Ming; Sutthibutpong, Thana; Rujisamphan, Nopporn

2017-11-01

Visualizing and controlling the phase separation of the donor and acceptor domains in organic bulk-hetero-junction (BHJ) solar devices made with poly([4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2-ethyl-hexyl)carbon-yl]thieno[3,4-bthiophenediyl]) (PTB7) and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) are needed to achieve high power conversion efficiency (PCE). Traditional bright-field (BF) imaging, especially of polymeric materials, produces images of poor contrast when done at the nanoscale level. Clear nanoscale morphologies of the PTB7:PC71BM blends prepared with different 1,8-diiodooctane (DIO) concentrations were seen when using the energy-filtered transmission electron microscopy (EFTEM). The electron energy loss (EELS) spectra of the pure PTB7 and PC71BM samples are centered at 22.7 eV and 24.5 eV, respectively. Using the electrons whose energy losses are in the range of 16-30 eV, detail information of the phase morphology at the nanoscale was obtained. Correlations between the improvement in the photovoltaic performances and the increased electron mobility were seen. These correlations are discussed in terms of the changes (at the nanoscale level) in blending phase morphology when different DIO concentrations are added.

SIMPLE MEASURES ARE AS EFFECTIVE AS INVASIVE TECHNIQUES IN THE DIAGNOSIS OF PULMONARY TUBERCULOSIS IN MALAWI

PubMed Central

Bell, David J; Dacombe, Russell; Graham, Stephen M; Hicks, Alexander; Cohen, Danielle; Chikaonda, Tarsizio; French, Neil; Molyneux, Malcolm E; Zijlstra, Ed E; Squire, S Bertel; Gordon, Stephen B

2010-01-01

Setting Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital for tuberculosis control. Methods to augment sputum collection are available but their additional benefit is uncertain in resource-limited settings. Objective To compare the diagnostic yields using five methods to obtain sputum from adults diagnosed with smear-negative PTB in Malawi. Design Self-expectorated sputum was collected under supervision for microscopy and mycobacterial culture in the study laboratory. Confirmed smear-negative patients, provided physiotherapy-assisted sputum and induced sputum followed, the next morning, by gastric washing and bronchoalveolar-lavage samples. Results 150 patients, diagnosed with smear-negative PTB by the hospital service, were screened. 39 (26%) were smear-positive from supervised self-expectorated sputum examined in the study laboratory. The remaining 111 confirmed smear-negative patients were enrolled; 89% were HIV positive. Seven additional smear-positive cases were diagnosed using the augmented sputum collection techniques. No differences were observed in the numbers of cases detected using the different methods. 44 (95.6%) of the 46 smear-positive cases could be detected from self-expectorated and physiotherapy-assisted samples Conclusions For countries like Malawi, the best use of limited resources to detect smear-positive PTB cases would be to improve the quality of self-expectorated sputum collection and microscopy. The additional diagnostic yield using bronchoalveolar-lavage after induced sputum is limited. PMID:19105886

An epidemiological assessment of the effect of ambient temperature on the incidence of preterm births: Identifying windows of susceptibility during pregnancy.

PubMed

Zheng, Xiangrong; Zhang, Weishe; Lu, Chan; Norbäck, Dan; Deng, Qihong

2018-05-01

It is well known that exposure to thermal stress during pregnancy can lead to an increased incidence of premature births. However, there is little known regarding window(s) of susceptibility during the course of a pregnancy. We attempted to identify possible windows of susceptibility in a cohort study of 3604 children in Changsha with a hot-summer and cold winter climatic characteristics. We examined the association between PTB and ambient temperature during different timing windows of pregnancy: conception month, three trimesters, birth month and entire pregnancy. We found a U-shaped relation between the prevalence of PTB and mean ambient temperature during pregnancy. Both high and low temperatures were associated with PTB risk, adjusted OR (95% CI) respectively 2.57 (1.98-3.33) and 2.39 (1.93-2.95) for 0.5 °C increase in high temperature range (>18.2°C) and 0.5°C decrease in low temperature range (< 18.2°C). Specifically, PTB was significantly associated with ambient temperature and extreme heat/cold days during conception month and the third trimester. Sensitivity analysis indicated that female fetus were more susceptible to the risk of ambient temperature. Our study indicates that the risk of preterm birth due to high or low temperature may exist early during the conception month. Copyright © 2018 Elsevier Ltd. All rights reserved.

Community education on preterm birth. Does it change practice?

PubMed Central

Sprague, Ann; Stewart, Paula; Niday, Patricia; Nimrod, Carl; Walker, Robin

2002-01-01

OBJECTIVE: To evaluate how well physicians and other prenatal care providers educate women about early recognition of and appropriate response to the signs and symptoms of preterm labour (PTL). To assess use of antenatal steroids for babies born at less than 34 weeks' gestation. DESIGN: Before-after study using a population-based approach. SETTING: Health care providers' offices, hospitals, and prenatal classes in Ottawa, Ont. PARTICIPANTS: Prenatal care providers, women in hospital after giving birth, prenatal class participants. INTERVENTIONS: Prenatal care providers received information and educational materials on PTL and preterm birth (PTB). They passed this information on to pregnant women at their 18- to 20-week prenatal visits. Teachers of prenatal classes gave the same information in early-series classes. Clinical practice guidelines were developed, and hospital staff received education on appropriate response to PTL. MAIN OUTCOME MEASURES: Use of educational materials and steroid treatment. RESULTS: Statistically significant increases were seen in the numbers of care providers who had educational material about PTL and PTB, who reported giving the educational material to all women, and who reported discussing signs and symptoms of PTL and PTB with all women; women who reported that their care providers talked with them about PTL and PTB, and women delivering preterm (< 34 weeks) babies who received steroids. CONCLUSION: Providing knowledge and standardized educational materials to health care providers can help improve preventive practice for PTL and educate women about PTL. PMID:12046368

Community education on preterm birth. Does it change practice?

PubMed

Sprague, Ann; Stewart, Paula; Niday, Patricia; Nimrod, Carl; Walker, Robin

2002-04-01

To evaluate how well physicians and other prenatal care providers educate women about early recognition of and appropriate response to the signs and symptoms of preterm labour (PTL). To assess use of antenatal steroids for babies born at less than 34 weeks' gestation. Before-after study using a population-based approach. Health care providers' offices, hospitals, and prenatal classes in Ottawa, Ont. Prenatal care providers, women in hospital after giving birth, prenatal class participants. Prenatal care providers received information and educational materials on PTL and preterm birth (PTB). They passed this information on to pregnant women at their 18- to 20-week prenatal visits. Teachers of prenatal classes gave the same information in early-series classes. Clinical practice guidelines were developed, and hospital staff received education on appropriate response to PTL. Use of educational materials and steroid treatment. Statistically significant increases were seen in the numbers of care providers who had educational material about PTL and PTB, who reported giving the educational material to all women, and who reported discussing signs and symptoms of PTL and PTB with all women; women who reported that their care providers talked with them about PTL and PTB, and women delivering preterm (< 34 weeks) babies who received steroids. Providing knowledge and standardized educational materials to health care providers can help improve preventive practice for PTL and educate women about PTL.

Permeability and toxicity characteristics of L-cysteine and 2-methyl-thiazolidine-4-carboxylic acid in Caco-2 cells.

PubMed

Kartal-Hodzic, Alma; Marvola, Tuuli; Schmitt, Mechthild; Harju, Kirsi; Peltoniemi, Marikki; Sivén, Mia

2013-01-01

Acetaldehyde is a known mutagenic substance and has been classified as a group-one carcinogen by the WHO. It is possible to bind acetaldehyde locally in the gastrointestinal (GI) tract with the semi-essential amino acid l-cysteine, which reacts covalently with acetaldehyde and forms compound 2-methyl-thiozolidine-4-carboxylic acid (MTCA). The Caco-2 cell line was used to determine the permeation of l-cysteine and MTCA, as well as the possible cell toxicity of both substances. Neither of the substances permeated through the Caco-2 cells at the concentrations used in this study, and only the highest concentration of MTCA affected the viability of the cells in the MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide) test. These results showed that when l-cysteine is administered in formulations releasing it locally in the lower parts of GI tract, it is not absorbed but can react with acetaldehyde, and that neither l-cysteine nor MTCA is harmful to the cells when present locally in the upper parts of GI tract. This study also shows that MTCA is sensitive at a lower pH of 5.5. Since stable MTCA is desired in different parts of the GI tract, this observation raises concern over the influence of lower pH on l-cysteine-containing product ability to bind and eliminate carcinogenic acetaldehyde.

The associations between environmental quality and preterm birth in the United States, 2000-2005: a cross-sectional analysis.

PubMed

Rappazzo, Kristen M; Messer, Lynne C; Jagai, Jyotsna S; Gray, Christine L; Grabich, Shannon C; Lobdell, Danelle T

2015-06-09

Many environmental factors have been independently associated with preterm birth (PTB). However, exposure is not isolated to a single environmental factor, but rather to many positive and negative factors that co-occur. The environmental quality index (EQI), a measure of cumulative environmental exposure across all US counties from 2000-2005, was used to investigate associations between ambient environment and PTB. With 2000-2005 birth data from the National Center for Health Statistics for the United States (n = 24,483,348), we estimated the association between increasing quintiles of the EQI and county-level and individual-level PTB; we also considered environmental domain-specific (air, water, land, sociodemographic and built environment) and urban-rural stratifications. Effect estimates for the relationship between environmental quality and PTB varied by domain and by urban-rural strata but were consistent across county- and individual-level analyses. The county-level prevalence difference (PD (95% confidence interval) for the non-stratified EQI comparing the highest quintile (poorest environmental quality) to the lowest quintile (best environmental quality) was -0.0166 (-0.0198, -0.0134). The air and sociodemographic domains had the strongest associations with PTB; PDs were 0.0196 (0.0162, 0.0229) and -0.0262 (-0.0300, -0.0224) for the air and sociodemographic domain indices, respectively. Within the most urban strata, the PD for the sociodemographic domain index was 0.0256 (0.0205, 0.0307). Odds ratios (OR) for the individual-level analysis were congruent with PDs. We observed both strong positive and negative associations between measures of broad environmental quality and preterm birth. Associations differed by rural-urban stratum and by the five environmental domains. Our study demonstrates the use of a large scale composite environment exposure metric with preterm birth, an important indicator of population health and shows potential for future research.

Area-level poverty and preterm birth risk: A population-based multilevel analysis

PubMed Central

DeFranco, Emily A; Lian, Min; Muglia, Louis A; Schootman, Mario

2008-01-01

Background Preterm birth is a complex disease with etiologic influences from a variety of social, environmental, hormonal, genetic, and other factors. The purpose of this study was to utilize a large population-based birth registry to estimate the independent effect of county-level poverty on preterm birth risk. To accomplish this, we used a multilevel logistic regression approach to account for multiple co-existent individual-level variables and county-level poverty rate. Methods Population-based study utilizing Missouri's birth certificate database (1989–1997). We conducted a multilevel logistic regression analysis to estimate the effect of county-level poverty on PTB risk. Of 634,994 births nested within 115 counties in Missouri, two levels were considered. Individual-level variables included demographics factors, prenatal care, health-related behavioral risk factors, and medical risk factors. The area-level variable included the percentage of the population within each county living below the poverty line (US census data, 1990). Counties were divided into quartiles of poverty; the first quartile (lowest rate of poverty) was the reference group. Results PTB < 35 weeks occurred in 24,490 pregnancies (3.9%). The rate of PTB < 35 weeks was 2.8% in counties within the lowest quartile of poverty and increased through the 4th quartile (4.9%), p < 0.0001. High county-level poverty was significantly associated with PTB risk. PTB risk (< 35 weeks) was increased for women who resided in counties within the highest quartile of poverty, adjusted odds ratio (adjOR) 1.18 (95% CI 1.03, 1.35), with a similar effect at earlier gestational ages (< 32 weeks), adjOR 1.27 (95% CI 1.06, 1.52). Conclusion Women residing in socioeconomically deprived areas are at increased risk of preterm birth, above other underlying risk factors. Although the risk increase is modest, it affects a large number of pregnancies. PMID:18793437

Area-level poverty and preterm birth risk: a population-based multilevel analysis.

PubMed

DeFranco, Emily A; Lian, Min; Muglia, Louis A; Schootman, Mario

2008-09-15

Preterm birth is a complex disease with etiologic influences from a variety of social, environmental, hormonal, genetic, and other factors. The purpose of this study was to utilize a large population-based birth registry to estimate the independent effect of county-level poverty on preterm birth risk. To accomplish this, we used a multilevel logistic regression approach to account for multiple co-existent individual-level variables and county-level poverty rate. Population-based study utilizing Missouri's birth certificate database (1989-1997). We conducted a multilevel logistic regression analysis to estimate the effect of county-level poverty on PTB risk. Of 634,994 births nested within 115 counties in Missouri, two levels were considered. Individual-level variables included demographics factors, prenatal care, health-related behavioral risk factors, and medical risk factors. The area-level variable included the percentage of the population within each county living below the poverty line (US census data, 1990). Counties were divided into quartiles of poverty; the first quartile (lowest rate of poverty) was the reference group. PTB < 35 weeks occurred in 24,490 pregnancies (3.9%). The rate of PTB < 35 weeks was 2.8% in counties within the lowest quartile of poverty and increased through the 4th quartile (4.9%), p < 0.0001. High county-level poverty was significantly associated with PTB risk. PTB risk (< 35 weeks) was increased for women who resided in counties within the highest quartile of poverty, adjusted odds ratio (adj OR) 1.18 (95% CI 1.03, 1.35), with a similar effect at earlier gestational ages (< 32 weeks), adj OR 1.27 (95% CI 1.06, 1.52). Women residing in socioeconomically deprived areas are at increased risk of preterm birth, above other underlying risk factors. Although the risk increase is modest, it affects a large number of pregnancies.

Timing of global regression and microbial bloom linked with the Permian-Triassic boundary mass extinction: implications for driving mechanisms

NASA Astrophysics Data System (ADS)

Baresel, Bjoern; Bucher, Hugo; Bagherpour, Borhan; Brosse, Morgane; Guodun, Kuang; Schaltegger, Urs

2017-04-01

High-precision U-Pb dating of single-zircon crystals by chemical abrasion-isotope dilution-thermal ionization mass spectrometry (CA-ID-TIMS) is applied to volcanic beds that are intercalated in sedimentary sequences across the Permian-Triassic boundary (PTB). By assuming that the zircon crystallization age closely approximate that of the volcanic eruption and subsequent deposition, U-Pb zircon geochronology is the preferred approach for dating abiotic and biotic events, such as the formational PTB and the Permian-Triassic boundary mass extinction (PTBME). We will present new U-Pb zircon dates for a series of volcanic ash beds in shallow-marine Permian-Triassic sections in the Nanpanjiang Basin, South China. These high-resolution U-Pb dates indicate a duration of 90 ± 38 kyr for the Permian sedimentary hiatus and a duration of 13 ± 57 kyr for the overlying Triassic microbial limestone in the shallow water settings of the Nanpanjiang pull apart Basin. The age and duration of the hiatus coincides with the formational PTB and the extinction interval in the Meishan Global Stratotype Section and Point, thus strongly supporting a glacio-eustatic regression, which best explains the genesis of the worldwide hiatus straddling the PTB in shallow water records. In adjacent deep marine troughs, rates of sediment accumulation display a six-fold decrease across the PTB compatible with a dryer and cooler climate during the Griesbachian as indicated by terrestrial plants. Our model of the PTBME hinges on the synchronicity of the hiatus with the onset of the Siberian Traps volcanism. This early eruptive phase likely released sulfur-rich volatiles into the stratosphere, thus simultaneously eliciting a short-lived ice age responsible for the global regression and a brief but intense acidification. Abrupt cooling, shrunk habitats on shelves and acidification may all have synergistically triggered the PTBME. Subsequently, the build-up of volcanic CO2 induced this transient cool climate whose early phase saw the deposition of the microbial limestone.

Altered expression of histone deacetylases, inflammatory cytokines and contractile-associated factors in uterine myometrium of Long Evans rats gestationally exposed to benzo[a]pyrene

PubMed Central

Laknaur, Archana; Foster, Terri-Lee; Bobb, Lesley E.; Ramesh, Aramandla; Ladson, Gwinnett M.; Hood, Darryl B.; Al-Hendy, Ayman; Thota, Chandrasekhar

2017-01-01

Etiology of preterm birth (PTB) is multifactorial; therefore, decreasing the incidence of PTB is a major challenge in the field of obstetrics. Epidemiological studies have reported an association between toxicants and PTB. However, there are no studies on the role of benzo[a]pyrene (BaP), an environmental toxicant, in the incidence of PTB. We first assessed the effects of BaP (150 and 300 μg kg−1 body weight) dosed via gavage from day 14 to 17 of pregnancy on gestation length in Long Evans rats. We further assessed the histopathology of the uterus, expression of inflammatory cytokines, contractile-associated factors, histone deacetylases (HDACs) and NFқB-p65 in myometrium collected on day 22 postpartum versus vehicle-treated controls. In our study, rats exposed to BaP delivered prematurely (P < 0.05) compared to control. Hematoxylin and eosin staining of uterus showed squamous metaplasia, glandular and stromal hyperplasia in BaP-exposed rats versus control. The concentrations of BaP metabolites measured by high-pressure liquid chromatography were higher in uterine myometrium of BaP-exposed rats while they were undetectable in controls. Quantitative real-time polymerase chain reaction showed significant increases in mRNA expression of interleukin-1β and -8, tumor necrosis factor-α, connexin 43, cyclo-oxygenase-2 and prostaglandin F2α receptor as compared to controls (P < 0.05). Western blot analysis revealed that BaP exposure caused decreases in class I HDACs 1 and 3 and increases in class II HDAC 5, cyclo-oxygenase-2 and nuclear translocation of NFκB-p65 relative to controls. Our results suggest that gestational exposure to BaP increases incidence of PTB through epigenetic changes that causes increases in the expression of contractile-associated factors through the NFκB pathway. PMID:26358852

Adverse pregnancy outcomes after in vitro fertilization: effect of number of embryos transferred and plurality at conception.

PubMed

Luke, Barbara; Stern, Judy E; Kotelchuck, Milton; Declercq, Eugene R; Hornstein, Mark D; Gopal, Daksha; Hoang, Lan; Diop, Hafsatou

2015-07-01

To evaluate risks for adverse pregnancy outcomes by number of embryos transferred (ET) and fetal heartbeats (FHB) in assisted reproductive technology-conceived singleton live births. Longitudinal cohort using cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System between 2004 and 2008 among women who were treated and gave birth in Massachusetts. Not applicable. Assisted reproductive technology data on 6,073 births between 2004 and 2008 were linked to vital records and hospital data. Likelihood of ET ≥3 vs. 1-2, FHB >1 vs. 1, and risks of preterm birth (PTB, <37 weeks' gestation), low birth weight (LBW, <2,500 g), and small-for-gestational-age birth weight (SGA, <10th percentile) with FHB >1 were modeled with binary logistic regression using a backward-stepping algorithm, and presented as adjusted odds ratios (95% confidence intervals). None. ET ≥3, FHB >1, PTB, LBW, and SGA. Higher ET was significantly more likely with older maternal age, intracytoplasmic sperm injection, assisted hatching, cleavage-stage embryos, and thawed embryos. The likelihood of FHB >1 with ≥3 ET vs. 1-2 ET was 2.04 (1.68-2.48). Risks of PTB and LBW with FHB >1 were 1.63 (1.27-2.09) and 1.81 (1.36-2.39), respectively; the risk of SGA was not significant. Nulliparity was associated with higher risks of PTB (1.34 [1.12-1.59]), LBW (1.48 [1.20-1.83]), and SGA (2.17 [1.69-2.78]). Number of embryos transferred was strongly associated with FHBs, with twice the risk of FHB >1 with ≥3 ET vs. 1-2 ET. Increasing FHBs were associated with significantly greater risks for PTB and LBW outcomes. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function.

PubMed

Hemingway, Cheryl; Berk, Maurice; Anderson, Suzanne T; Wright, Victoria J; Hamilton, Shea; Eleftherohorinou, Hariklia; Kaforou, Myrsini; Goldgof, Greg M; Hickman, Katy; Kampmann, Beate; Schoeman, Johan; Eley, Brian; Beatty, David; Pienaar, Sandra; Nicol, Mark P; Griffiths, Michael J; Waddell, Simon J; Newton, Sandra M; Coin, Lachlan J; Relman, David A; Montana, Giovanni; Levin, Michael

2017-01-01

The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies.

Bed rest and activity restriction for women at risk for preterm birth: a survey of Canadian prenatal care providers.

PubMed

Sprague, Ann E; O'Brien, Beverley; Newburn-Cook, Christine; Heaman, Maureen; Nimrod, Carl

2008-04-01

To explore the practices of Canadian obstetricians, family physicians, and midwives in recommending bed rest or activity restriction for women at risk for preterm birth (PTB) and to assess the decisional conflict experienced by care providers when they recommend these therapies. A self-administered mail survey of prenatal care providers was carried out using Dillman's Tailored Design Method. Analysis included descriptive statistics and analysis of variance. The survey was distributed to 1441 potential participants; of these, 1172 were eligible participants, and 516 (44.2%) completed the survey. For women at risk of PTB, 60 of 170 obstetricians (35%), 88 of 206 family practitioners (42.7%), and 30 of 140 midwives (21.4%) recommended bed rest in hospital; 110 of 170 obstetricians (64.7%), 144 of 206 family practitioners (69.9%), and 73 of 140 midwives (52.1%) recommended bed rest at home. These recommendations occurred despite the response from about two thirds of each professional group that the effectiveness of bed rest was in the fair-to-poor range in helping to prevent PTB. The mean score on the Provider Decision Process Assessment Instrument, measuring decisional conflict for all care provider groups, was 30 (SD 7.4) (possible score range 12-60). There were no significant differences in decisional conflict scores among provider groups (F [2,347] = 2.24; P = 0.11). Care providers have been discouraged from routinely recommending bed rest for women at risk of PTB because of potential adverse side effects. This study demonstrates that most Canadian prenatal care providers have not been persuaded to incorporate these recommendations into practice. Except for women with multiple gestation, there is inconsistent practice in recommending bed rest and activity restriction. Additionally, Canadian prenatal care providers have some decisional conflict about using this therapy. These results provide some of the first Canadian perspectives on the practice of prescribing therapeutic bed rest for PTB.

TWSTFT Link Calibration Report

DTIC Science & Technology

2015-09-01

1 Annex II. TWSTFT link calibration with a GPS calibrator Calibration reference: CI-888-2015 Version history: ZJ/V0/25Feb2015, V0a,b/HE/ZJ...7Mar; V0s/VZ9Mar; V0d,e,f+/DM10,17Mar; V1.0/1Apr; Final version 1Sept2015 TWSTFT link calibration report -- Calibration of the Lab(k)-PTB UTC...bipm.org * Coordinator Abstract This report includes the calibration results of the Lab(k)-PTB TWSTFT link and closure measurements of the BIPM

PTB’S Time and Frequency Activities in 2006: New DCF77 Electronics, New NTP Servers, and Calibration Activities

DTIC Science & Technology

2007-01-01

PTTI) Meeting ( TWSTFT ) is being routinely performed with several European and US stations. On the initiative of NICT, a TWSTFT link was...During the last 2 years, PTB has upgraded its TWSTFT and GPS capabilities in order to achieve better reliability and robustness against system failures...NTP-server, and, briefly, the calibration of the international time links, i.e. the result of the latest calibration of the TWSTFT links to the USNO

BQ-123 prevents LPS-induced preterm birth in mice via the induction of uterine and placental IL-10.

PubMed

Olgun, Nicole S; Hanna, Nazeeh; Reznik, Sandra E

2015-02-01

Preterm birth (PTB), defined as any delivery occurring prior to the completion of 37 weeks' gestation, currently accounts for 11-12% of all births in the United States. Maternal genito-urinary infections account for up to 40% of all PTBS and induce a pro-inflammatory state in the host. The potent vasoconstrictor Endothelin-1 (ET-1) is known to be upregulated in the setting of infection, and elicits its effect by binding to the ETA receptor. We have previously shown that antagonism of the ETA receptor with BQ-123 is capable of preventing LPS-induced PTB in mice. We hypothesize that the administration of BQ-123 post LPS exposure will dismantle a positive feedback loop observed with pro-inflammatory cytokines upstream of ET-1. On GD 15.5, pregnant C57BL/6 mice were injected with PBS, LPS, BQ-123, or LPS+BQ-123. Changes at both the level of transcription and translation were observed in uterus and placenta in the ET-1 axis and in pro- and anti-inflammatory cytokines over the course of 12h. We discovered that BQ-123, when administered 10h post LPS, is capable of increasing production of uterine and placental Interleukin-10, causing a shift away from the pro-inflammatory state. We also observed that antagonism of the ETA receptor decreased IL-1β and TNFα in the placenta while also decreasing transcription of ET-1 in the uterus. Our results reinforce the role of ET-1 at the maternal fetal interface and highlight the potential benefit of ETA receptor blockade via the suppression of ET-1, and induction of a Th2 cytokine dominant state. Copyright © 2014. Published by Elsevier Inc.

Pre-term birth and low birth weight following preimplantation genetic diagnosis: analysis of 88 010 singleton live births following PGD and IVF cycles.

PubMed

Sunkara, Sesh Kamal; Antonisamy, Belavendra; Selliah, Hepsy Y; Kamath, Mohan S

2017-02-01

Is PGD associated with the risk of adverse perinatal outcomes such as pre-term birth (PTB) and low birth weight (LBW)? There was no increase in the risk of adverse perinatal outcomes of PTB, and LBW following PGD compared with autologous IVF. Pregnancies resulting from ART are associated with a higher risk of pregnancy complications compared with spontaneously conceived pregnancies. The possible reason of adverse obstetric outcomes following ART has been attributed to the underlying infertility itself and embryo specific epigenetic modifications due to the IVF techniques. It is of interest whether interventions such as embryo biopsy as performed in PGD affect perinatal outcomes. Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of ART in the UK. The HFEA has collected data prospectively on all ART performed in the UK since 1991. Data from 1996 to 2011 involving a total of 88 010 singleton live births were analysed including 87 571 following autologous stimulated IVF ± ICSI and 439 following PGD cycles. Data on all women undergoing either a stimulated fresh IVF ± ICSI treatment cycle or a PGD cycle during the period from 1996 to 2011 were analysed to compare perinatal outcomes of PTB and LBW among singleton live births. Logistic regression analysis was performed adjusting for female age category, year of treatment, previous IVF cycles, infertility diagnosis, number of oocytes retrieved, whether IVF or ICSI was used and day of embryo transfer. There was no increase in the risk of PTB and LBW following PGD versus autologous stimulated IVF ± ICSI treatment, unadjusted odds of PTB (odds ratio (OR) 0.68, 95% CI: 0.46-0.99) and LBW (OR 0.56, 95% CI: 0.37-0.85). After adjusting for the potential confounders, there was again no increase in the risk of the adverse perinatal outcomes following PGD: PTB (adjusted odds ratio (aOR) 0.66, 95% CI: 0.45-0.98) and LBW (aOR 0.58, 95% CI: 0.38-0.88). Although the analysis was adjusted for a number of important confounders, the data set had no information on confounders such as smoking, body mass index and the medical history of women during pregnancy to allow adjustment. There was no information on the stage of embryo at biopsy, whether blastomere or trophectoderm biopsy. The demonstration that PGD is not associated with higher risk of PTB and LBW provides reassurance towards its current expanding application. No funding was obtained. There are no competing interests to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Design and evaluation of an economic taste-masked dispersible tablet of pyridostigmine bromide, a highly soluble drug with an extremely bitter taste.

PubMed

Tan, Qunyou; Zhang, Li; Zhang, Liangke; Teng, Yongzhen; Zhang, Jingqing

2012-01-01

Pyridostigmine bromide (PTB) is a highly soluble and extremely bitter drug. Here, an economic complexation technology combined with direct tablet compression method has been developed to meet the requirements of a patient friendly dosage known as taste-masked dispersible tablets loaded PTB (TPDPTs): (1) TPDPTs should have optimal disintegration and good physical resistance (hardness); (2) a low-cost, simple but practical preparation method suitable for industrial production is preferred from a cost perspective. Physicochemical properties of the inclusion complex of PTB with beta-cyclodextrin were investigated by Fourier transformed infrared spectroscopy, differential scanning calorimetry and UV spectroscopy. An orthogonal design was chosen to properly formulate TPDPTs. All volunteers regarded acceptable bitterness of TPDPTs. The properties including disintegration time, weight variation, friability, hardness, dispersible uniformity and drug content of TPDPTs were evaluated. The dissolution profile of TPDPTs in distilled water exhibited a fast rate. Pharmacokinetic results demonstrated that TPDPTs and the commercial tablets were bioequivalent.

Pathophysiology of preterm labor with intact membranes.

PubMed

Talati, Asha N; Hackney, David N; Mesiano, Sam

2017-11-01

Preterm labor with intact membranes is a major cause of spontaneous preterm birth (sPTB). To prevent sPTB a clear understanding is needed of the hormonal interactions that initiate labor. The steroid hormone progesterone acting via its nuclear progesterone receptors (PRs) in uterine cells is essential for the establishment and maintenance of pregnancy and disruption of PR signaling (i.e., functional progesterone/PR withdrawal) is key trigger for labor. The process of parturition is also associated with inflammation within the uterine tissues and it is now generally accepted that inflammatory stimuli from multiple extrinsic and intrinsic sources induce labor. Recent studies suggest inflammatory stimuli induce labor by affecting PR transcriptional activity in uterine cells to cause functional progesterone/PR withdrawal. Advances in understanding the functional interaction of inflammatory load on the pregnancy uterus and progesterone/PR signaling is opening novel areas of research and may lead to rational therapeutic strategies to effectively prevent sPTB. Copyright © 2017 Elsevier Inc. All rights reserved.

Pressure-induced multiband superconductivity in pyrite PtB i2 with perfect electron-hole compensation

NASA Astrophysics Data System (ADS)

Chen, Xuliang; Shao, Dexi; Gu, Chuanchuan; Zhou, Yonghui; An, Chao; Zhou, Ying; Zhu, Xiangde; Chen, Tong; Tian, Mingliang; Sun, Jian; Yang, Zhaorong

2018-05-01

We report on the discovery of pressure-induced superconductivity in the compensated semimetal pyrite PtB i2 , which exhibits extreme magnetoresistance (XMR) and nontrivial band structure at ambient pressure. The appearance of superconductivity, first observed at PC˜13 GPa with an onset critical temperature TC of ˜2.2 K , is accompanied by a pronounced enhancement of the density of electrons and holes based on Hall-effect measurements. Upon further compression, TC remains almost unchanged up to 50.0 GPa; remarkably, the perfect electron-hole compensation still holds, while the carrier mobility greatly reduces. No evident trace of structural phase transitions is detected through synchrotron x-ray diffraction over the measured pressure range of 1.5-51.2 GPa. These results highlight a multiband characteristic of the observed superconductivity, making pyrite PtB i2 unique among the compensated XMR materials where the pressure-induced superconductivity usually links to structural transitions and carrier imbalance.

Study of series-connected polymer tandem solar cells based on a highly efficient donor material of PTB7-Th

NASA Astrophysics Data System (ADS)

Zang, Yue; Gao, Xiumin; Xin, Qing; Lin, Jun; Zhao, Jufeng

2017-06-01

A highly efficient donor polymer, PTB7-Th, combined with acceptor fullerene PC71BM was introduced as the subcell in the series-connected tandem devices to achieve high-performance polymer tandem solar cells. Design of the device architecture was investigated using modeling and simulation methods to identify the optimal structure and to predict performance of the tandem cells. To address the challenge of current matching between the constituent subcells, the effect of active layer thickness, different device structure, and use of ultrathin Ag film were analyzed. It was found that the distribution of optical intensity in the tandem structure can be optimized through the optical spacer effect of interfacial layers and micro-cavity effect derived from the embedded ultrathin Ag film. Our results indicate that the efficient light utilization with appropriate subcells can allow achievement of power conversion efficiency of 12%, which can be 25% higher than that of a single cell of PTB7-Th.

Improved GPS-based time link calibration involving ROA and PTB.

PubMed

Esteban, Héctor; Palacio, Juan; Galindo, Francisco Javier; Feldmann, Thorsten; Bauch, Andreas; Piester, Dirk

2010-03-01

The calibration of time transfer links is mandatory in the context of international collaboration for the realization of International Atomic Time. In this paper, we present the results of the calibration of the GPS time transfer link between the Real Instituto y Observatorio de la Armada (ROA) and the Physikalisch-Technische Bundesanstalt (PTB) by means of a traveling geodetic-type GPS receiver and an evaluation of the achieved type A and B uncertainty. The time transfer results were achieved by using CA, P3, and also carrier phase PPP comparison techniques. We finally use these results to re-calibrate the two-way satellite time and frequency transfer (TWSTFT) link between ROA and PTB, using one month of data. We show that a TWSTFT link can be calibrated by means of GPS time comparisons with an uncertainty below 2 ns, and that potentially even sub-nanosecond uncertainty can be achieved. This is a novel and cost-effective approach compared with the more common calibration using a traveling TWSTFT station.

Modeling the Free Carrier Recombination Kinetics in PTB7:PCBM Organic Photovoltaics

DOE PAGES

Oosterhout, Stefan D.; Ferguson, Andrew J.; Larson, Bryon W.; ...

2016-10-03

Currently the exact recombination mechanism of free carriers in organic photovoltaic (OPV) devices is poorly understood. Often a reduced Langevin model is used to describe the decay behavior of electrons and holes. Here we propose a novel, simple kinetic model that accurately describes the decay behavior of free carriers in the PTB7:PCBM organic photovoltaic blend. In order to accurately describe the recombination behavior of free carriers as measured by time-resolved microwave conductivity (TRMC), this model needs to only take into account free and trapped holes in the polymer, and free electrons in the fullerene. The model is consistent for differentmore » PTB7:PCBM blend ratios and spans a light intensity range of over 3 orders of magnitude. Furthermore, the model demonstrates that dark carriers exist in the polymer and interact with photoinduced charge carriers, and that the trapping and detrapping rates of the holes are of high importance to the overall carrier lifetime.« less

Analysis of polyglutamine-coding repeats in the TATA-binding protein in different human populations and in patients with schizophrenia an bipolar affective disorder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubinsztein, D.C.; Leggo, J.; Crow, T.J.

A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close tomore » the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tract-lengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus. 22 refs., 1 tab.« less

Disparities in Maternal Child and Health Outcomes Attributable to Prenatal Tobacco Use.

PubMed

Mohlman, Mary Katherine; Levy, David T

2016-03-01

Previous estimates of smoking-attributable adverse outcomes, such as preterm births (PTBs), low birth weight (LBW) and Sudden Infant Death Syndrome (SIDs) generally do not address disparities by maternal age, racial/ethnic group or socioeconomic status (SES). This study develops estimates of smoking-attributable PTB, LBW and SIDS for the US by age, SES and racial/ethnic groupings. Data on the number of births and the prevalence of PTB, LBW and SIDS were used to develop the number of outcomes by age, race/ethnicity, and SES. The prevalence of prenatal smoking by age, race/ethnic and education and the relative risk of outcomes for smokers were used to calculate smoking-attributable fractions of outcomes. Prenatal smoking among ages 15-24 is above 12 %, with 20-24 year olds representing at least 35 % of PTB, LBW SIDS cases. Women with a high school education or less represented more than 50 % of PTB and LBW births, and 44 % of SIDS cases. While non-Hispanic Whites had the majority of smoking-attributable outcomes, non-Hispanic Blacks represented a disproportionately high percentage of PTBs (18 %), LBW births (22 %), and SIDS cases (13 %). Reducing prenatal smoking has the potential to reduce adverse birth outcomes and costs with long-term implications, especially among the young, non-Hispanic Blacks and those of lower SES. Stricter tobacco control policies, especially higher cigarette taxes, higher minimum purchase ages for tobacco and improved cessation interventions can help reduce disparities and the cost to insurers, especially public costs through Medicaid.

Risk for latent and active tuberculosis in Germany.

PubMed

Herzmann, Christian; Sotgiu, Giovanni; Bellinger, Oswald; Diel, Roland; Gerdes, Silke; Goetsch, Udo; Heykes-Uden, Helga; Schaberg, Tom; Lange, Christoph

2017-06-01

Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany. Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs. From 2008-2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up. Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis.

Assessment of critical exposure and outcome windows in time-to-event analysis with application to air pollution and preterm birth study.

PubMed

Chang, Howard H; Warren, Joshua L; Darrow, Lnydsey A; Reich, Brian J; Waller, Lance A

2015-07-01

In reproductive epidemiology, there is a growing interest to examine associations between air pollution exposure during pregnancy and the risk of preterm birth (PTB). One important research objective is to identify critical periods of exposure and estimate the associated effects at different stages of pregnancy. However, population studies have reported inconsistent findings. This may be due to limitations from the standard analytic approach of treating PTB as a binary outcome without considering time-varying exposures together over the course of pregnancy. To address this research gap, we present a Bayesian hierarchical model for conducting a comprehensive examination of gestational air pollution exposure by estimating the joint effects of weekly exposures during different vulnerable periods. Our model also treats PTB as a time-to-event outcome to address the challenge of different exposure lengths among ongoing pregnancies. The proposed model is applied to a dataset of geocoded birth records in the Atlanta metropolitan area between 1999-2005 to examine the risk of PTB associated with gestational exposure to ambient fine particulate matter [Formula: see text]m in aerodynamic diameter (PM[Formula: see text]). We find positive associations between PM[Formula: see text] exposure during early and mid-pregnancy, and evidence that associations are stronger for PTBs occurring around week 30. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Contrasting microbial community changes during mass extinctions at the Middle/Late Permian and Permian/Triassic boundaries

NASA Astrophysics Data System (ADS)

Xie, Shucheng; Algeo, Thomas J.; Zhou, Wenfeng; Ruan, Xiaoyan; Luo, Genming; Huang, Junhua; Yan, Jiaxin

2017-02-01

Microbial communities are known to expand as a result of environmental deterioration during mass extinctions, but differences in microbial community changes between extinction events and their underlying causes have received little study to date. Here, we present a systematic investigation of microbial lipid biomarkers spanning ∼20 Myr (Middle Permian to Early Triassic) at Shangsi, South China, to contrast microbial changes associated with the Guadalupian-Lopingian boundary (GLB) and Permian-Triassic boundary (PTB) mass extinctions. High-resolution analysis of the PTB crisis interval reveals a distinct succession of microbial communities based on secular variation in moretanes, 2-methylhopanes, aryl isoprenoids, steranes, n-alkyl cyclohexanes, and other biomarkers. The first episode of the PTB mass extinction (ME1) was associated with increases in red algae and nitrogen-fixing bacteria along with evidence for enhanced wildfires and elevated soil erosion, whereas the second episode was associated with expansions of green sulfur bacteria, nitrogen-fixing bacteria, and acritarchs coinciding with climatic hyperwarming, ocean stratification, and seawater acidification. This pattern of microbial community change suggests that marine environmental deterioration was greater during the second extinction episode (ME2). The GLB shows more limited changes in microbial community composition and more limited environmental deterioration than the PTB, consistent with differences in species-level extinction rates (∼71% vs. 90%, respectively). Microbial biomarker records have the potential to refine our understanding of the nature of these crises and to provide insights concerning possible outcomes of present-day anthropogenic stresses on Earth's ecosystems.

High bisphenol A (BPA) concentration in the maternal, but not fetal, compartment increases the risk of spontaneous preterm delivery.

PubMed

Behnia, Faranak; Peltier, Morgan; Getahun, Darios; Watson, Cheryl; Saade, George; Menon, Ramkumar

2016-11-01

The objective of this study is to determine if BPA exposure, as measured by maternal plasma (MP) and amniotic fluid (AF) BPA concentrations is associated with an increased risk of spontaneous preterm birth (PTB) and preterm premature rupture of membranes (pPROM). In this nested case-control study, MP samples from women in term labor (n = 30), preterm labor that ended with preterm delivery (n = 25), or who had pPROM (n = 30) and amniotic fluid samples from term labor (n= 45), preterm labor (n = 60), and pPROM (n = 35) were assayed for BPA by enzyme immunoassay. BPA was detectible in 100% of MP and AF samples. Women with MP BPA concentrations in the fourth quartile were at increased risk of PTB (cOR = 4.12, 95% CI = 1.32-12.87; aOR = 4.78, 95% CI = 1.14-20) but not pPROM. High (fourth quartile) AF BPA values also tended to increase the risk of pPROM (cOR = 2.47, 95% CI = 0.96-6.37) but results were not statistically significant. Increased BPA concentration is associated with an increased risk for PTB or pPROM depending on the maternal-fetal compartment(s) affected. High MP plasma BPA concentrations are associated with PTB with intact membranes but high AF BPA concentrations may weakly be associated with pPROM.

The CYP7A1 gene rs3808607 variant is associated with susceptibility of tuberculosis in Moroccan population

PubMed Central

Qrafli, Mounia; Amar, Youssef; Bourkadi, Jamaleddine; Ben Amor, Jouda; Iraki, Ghali; Bakri, Youssef; Amzazi, Saaîd; Lahlou, Ouafae; Seghrouchni, Fouad; El Aouad, Rajae; Sadki, Khalid

2014-01-01

Introduction Despite the medical progress in treatment. Tuberculosis (TB) continues to be a serious global health problem. A genome-wide linkage study identified a major susceptibility locus on chromosomal region 8q12-q13 in Moroccan TB patients. The CYP7A1 gene is located in this region and codes for cholesterol 7a-hydroxylase, an enzyme involved in cholesterol catabolism. Methods We selected three SNPs (rs3808607, rs8192875 and rs8192879) and studied their genotype and allele frequencies distribution in patients with pulmonary (PTB) or pleural TB (pTB), and compared them to Healthy Controls (HC). Genotyping of rs8192875 and rs8192879 SNPs was carried out using the Taq Man SNP genotyping Assay while rs3808607 was investigated by PCR-RFLP. Results We reported here for the first time a statistically significant increase in the AA homozygote genotype frequency of rs3808607 in PTB patients compared to HC (p = 0.02, OR = 1.93, 95% CI: 1.93 (1.07;3.49). The increased risk of developing TB was maintained when we combined the groups of patients (PTB-pTB) (p = 0.01, OR= 1.91, 95% CI = (1.07 - 3.42). In contrast, no genetic association was observed between the rs8192875 or rs8192879 polymorphisms and TB. Conclusion Our investigations suggest that rs3808607 may play a role in susceptibility to TB in a Moroccan population. PMID:25360185

High-risk of preterm birth and low birth weight after oocyte donation IVF: analysis of 133,785 live births.

PubMed

Kamath, Mohan Shashikant; Antonisamy, Belavendra; Mascarenhas, Mariano; Sunkara, Sesh Kamal

2017-09-01

A higher risk of pregnancy complications occurs after assisted reproductive techniques compared with spontaneously conceived pregnancies. This is attributed to the underlying infertility and assisted reproduction technique procedures involved during treatment. It is a matter of interest whether use of donor oocytes affects perinatal outcomes compared with pregnancies after autologous IVF. Anonymized data were obtained from the Human Fertilization and Embryology Authority. The analysis included 5929 oocyte donation and 127,856 autologous IVF live births. Data from all women who underwent donor oocyte recipient or autologous IVF cycles, both followed with fresh embryo transfer, were analysed to compare perinatal outcomes of preterm birth (PTB) and low birthweight (LBW) after singleton and multiple live births. The risk of adverse perinatal outcomes after oocyte donation was increased: adjusted OR (aOR) 1.56, 99.5% CI 1.34 to 1.80 for PTB and aOR 1.43, 99.5% CI 1.24 to 1.66 for LBW were significantly higher after oocyte donation compared with autologous IVF singletons. The adjusted odds PTB (aOR 1.21, 99.5% CI 1.02 to 1.43) was significantly higher after oocyte donation compared with autologous IVF multiple births. Analysis of this large dataset suggests significantly higher risk of PTB and LBW after ooctye donation compared with autologous IVF pregnancies. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Air pollution exposure and adverse pregnancy outcomes in a large UK birth cohort: use of a novel spatio-temporal modelling technique.

PubMed

Hannam, Kimberly; McNamee, Roseanne; Baker, Philip; Sibley, Colin; Agius, Raymond

2014-09-01

Previous work suggests an association between air pollution exposure and adverse pregnancy outcomes, even at relatively low concentrations. Our aim was to quantify the effect of air pollution having an adverse effect on preterm birth (PTB) and fetal growth in a large UK cohort using a novel exposure estimation technique [spatio-temporal (S-T) model] alongside a traditional nearest stationary monitor technique (NSTAT). All available postcodes from a Northwest England birth outcome dataset during 2004-2008 were geocoded (N=203 562 deliveries). Pollution estimates were linked to corresponding pregnancy periods using temporally adjusted background modelled concentrations as well as NSTAT. Associations with PTB, small for gestational age (SGA), and birth weight were investigated using regression models adjusting for maternal age, ethnicity, parity, birth season, socioeconomic status (SES), body mass index (BMI), and smoking. Based on the novel S-T model, a small statistically significant association was observed for particulate matter (PM10) and SGA, particularly with exposure in the first and third trimesters. Similar effects on SGA were also found for nitrogen dioxide (NO 2), particulate matter (PM 2,5), and carbon monoxide (CO) in later pregnancy, but no overall increased risk was observed. No associations were found with NO xor the outcomes PTB and reduction in birth weight. Our findings suggest an association between air pollution exposure and birth of a SGA infant, particularly in the later stages of pregnancy but not with PTB or mean birth weight change.

Prevalence of pulmonary tuberculosis among expatriates subjected to medical visa screening in Abu Dhabi, United Arab Emirates.

PubMed

Al Hosani, Farida I; Yahia, Ghada A

2013-03-01

All applicants for work and/or residence in Abu Dhabi are screened for tuberculosis at the time of issuing or renewing their residence visa. The purpose of this study is to assess the prevalence of TB among visa applicants and the likelihood of testing positive among different subgroups. Data from the electronic visa screening system was used for a total of 948,504 applicants screened for residence in Abu Dhabi from January to December 2010. The screening identified 4577 suspected cases of pulmonary tuberculosis (PTB); 1558 people with chest X-ray findings suggestive of prior PTB; 235 smear-positives; and 132 culture-positive cases. The prevalence of active PTB was 39/100,000, with new applicants significantly more likely to test positive compared with renewals (OR: 2.05, 95% CI: 1.5-2.7, P<.001). People coming from African countries had the highest prevalence of TB compared with people from other regions (OR: 21.25, 95% CI: 6.72-67.17, P<.001). The number of active PTB cases among applicants for visa screening is still of a real concern. Without a rigorous screening system, the disease can spread to the community and hit other people. Certain subgroups were more likely to have the disease; this could provide the scientific foundation for future amendments in the screening requirements. Copyright © 2012 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospital-based retrospective study.

PubMed

Sreeramareddy, Chandrashekhar T; Panduru, Kishore V; Verma, Sharat C; Joshi, Hari S; Bates, Michael N

2008-01-24

Studies from developed countries have reported on host-related risk factors for extra-pulmonary tuberculosis (EPTB). However, similar studies from high-burden countries like Nepal are lacking. Therefore, we carried out this study to compare demographic, life-style and clinical characteristics between EPTB and PTB patients. A retrospective analysis was carried out on 474 Tuberculosis (TB) patients diagnosed in a tertiary care hospital in western Nepal. Characteristics of demography, life-style and clinical features were obtained from medical case records. Risk factors for being an EPTB patient relative to a PTB patient were identified using logistic regression analysis. The age distribution of the TB patients had a bimodal distribution. The male to female ratio for PTB was 2.29. EPTB was more common at younger ages (< 25 years) and in females. Common sites for EPTB were lymph nodes (42.6%) and peritoneum and/or intestines (14.8%). By logistic regression analysis, age less than 25 years (OR 2.11 95% CI 1.12-3.68) and female gender (OR 1.69, 95% CI 1.12-2.56) were associated with EPTB. Smoking, use of immunosuppressive drugs/steroids, diabetes and past history of TB were more likely to be associated with PTB. Results suggest that younger age and female gender may be independent risk factors for EPTB in a high-burden country like Nepal. TB control programmes may target young and female populations for EPTB case-finding. Further studies are necessary in other high-burden countries to confirm our findings.

Impact of preterm birth on infant mortality for newborns with congenital heart defects: The EPICARD population-based cohort study.

PubMed

Laas, Enora; Lelong, Nathalie; Ancel, Pierre-Yves; Bonnet, Damien; Houyel, Lucile; Magny, Jean-François; Andrieu, Thibaut; Goffinet, François; Khoshnood, Babak

2017-05-15

Congenital heart defects (CHD) and preterm birth (PTB) are major causes of infant mortality. However, limited data exist on risk of mortality associated with PTB for newborns with CHD. Our objective was to assess impact of PTB on risk of infant mortality for newborns with CHD, while taking into account the role of associated anomalies and other potentially confounding factors. We used data on 2172 live births from a prospective population-based cohort study of CHD (the EPICARD Study) and compared neonatal, post-neonatal and overall infant mortality for infants born at <32, 32-34 and 35-36 weeks vs. those born at term (37-41 weeks). Preterm newborns had a 3.8-fold higher risk of infant death (17.9%) than term newborns (4.7%), RR 3.8, 95%CI 2.7-5.2; the risk associated with PTB was more than four-fold higher for neonatal (RR 4.3, 95% CI 2.9-6.6) and three-fold higher for post-neonatal deaths (RR 3.0, 95% CI 1.7-5.2). Survival analysis showed that newborns <35 weeks had a higher risk of mortality, which decreased but persisted after exclusion of associated anomalies and adjustment for potential confounders. Preterm birth is associated with an approximately four-fold higher risk of infant mortality for newborns with CHD. This excess risk appears to be mostly limited to newborns <35 weeks of gestation and is disproportionately due to early deaths.

Broadly neutralizing antibody specificities detected in the genital tract of HIV-1 infected women.

PubMed

Mkhize, Nonhlanhla N; Durgiah, Raveshni; Ashley, Vicki; Archary, Derseree; Garrett, Nigel J; Karim, Quarraisha Abdool; Karim, Salim S Abdool; Moore, Penny L; Yates, Nicole; Passmore, Jo-Ann S; Tomaras, Georgia D; Morris, Lynn

2016-04-24

Broadly neutralizing antibodies (bNAbs) targeting conserved epitopes on the HIV envelope glycoprotein have been identified in blood from HIV-1 infected women. We investigated whether antibodies in the genital tract from these women share similar epitope specificities and functional profiles as those in blood. Immunoglobulin (Ig)G and IgA antibodies were isolated from cervicovaginal lavages or Softcups from 13 HIV-infected women in the CAPRISA cohort using Protein G and Peptide M, respectively. Binding antibodies to envelope antigens were quantified by ELISA and binding antibody multiplex assay. Neutralizing antibody titers and epitope targets were measured using the TZM-bl assay with Env-pseudotyped wild-type and mutated viruses. HIV-specific IgG, but not IgA, was detected in genital secretions and the ratio of total IgG to HIV-specific IgG was similar to plasma. HIV-specific IgG reacted with multiple envelope antigens, including V1V2, gp120, gp140 and gp41. Two women had high plasma titers of HIV-specific IgG3 which was also detected in their genital tract samples. IgG from the genital tract had neutralizing activity against both Tier 1 and Tier 2 primary HIV-isolates. Antibodies targeting well known glycan epitopes and the membrane proximal region of gp41 were detected in genital secretions, and matched specificities in plasma. Women with plasma bNAbs have overlapping specificities in their genital secretions, indicating that these predominantly IgG isotype antibodies may transudate from blood to the genital tract. These data provide evidence that induction of systemic HIV-specific bNAbs can lead to antiviral immunity at the portal of entry.

Optical-Fiber Power Meter Comparison Between NIST and PTB.

PubMed

Vayshenker, I; Haars, H; Li, X; Lehman, J H; Livigni, D J

2003-01-01

We describe the results of a comparison of reference standards between the National Institute of Standards and Technology (NIST-USA) and Physikalisch-Technische Bundesanstalt (PTB-Germany) at nominal wavelengths of 1300 nm and 1550 nm using an optical-fiber cable. Both laboratories used thermal detectors as reference standards. A novel temperature-controlled, optical-trap detector was used as a transfer standard to compare two reference standards. Measurement results showed differences of less than 1.5 × 10(-3), which is within the combined uncertainty for both laboratories.

Avian pathogenic Escherichia coli bind fibronectin and laminin.

PubMed

Ramírez, Rosa María; Almanza, Yolanda; González, Rafael; García, Santos; Heredia, Norma

2009-04-01

Avian colisepticemia frequently occurs after respiratory tract damage, the primary site for infection allows bacteria to encounter an exposed basement membrane, where laminin and fibronectin are important components. We investigated the ability of an isolate of avian pathogenic Escherichia coli to bind fibronectin and laminin. Using Far-western dot blot analysis, we demonstrated the ability of this microorganism to bind basement membrane proteins fibronectin and laminin. Results from an ELISA-based approach indicate that the binding to these membrane proteins was bacterial-dose dependent. Furthermore, two specific E. coli polypeptides, of 32 kDa and 130 kDa, reacted with laminin and fibronectin, respectively. Further evaluation of these potential bacterial adhesins may provide insights into the pathogenesis of colibacillosis.

Substance P binding sites in the nucleus tractus solitarius of the cat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maley, B.E.; Sasek, C.A.; Seybold, V.S.

1988-11-01

Substance P binding sites in the nucleus tractus solitarius were visualized with receptor autoradiography using Bolton-Hunter (/sup 125/I)substance P. Substance P binding sites were found to have distinct patterns within the cat nucleus tractus solitarius. The majority of substance P binding sites were present in the medial, intermediate and the peripheral rim of the parvocellular subdivisions. Lower amounts of substance P binding sites were present in the commissural, ventrolateral, interstitial and dorsolateral subdivisions. No substance P binding sites were present in the central region of the parvocellular subdivision or the solitary tract. The localization of substance P binding sites inmore » the nucleus tractus solitarius is very similar to the patterns of substance P immunoreactive fibers previously described for this region. Results of this study add further support for a functional role of substance P in synaptic circuits of the nucleus tractus solitarius.« less

Final report on APMP.M.P-S4: Results of the bilateral supplementary comparison on pressure measurements in the range (60 to 350) kPa of gauge pressure in gas media

NASA Astrophysics Data System (ADS)

Priruenrom, T.; Sabuga, W.; Konczak, T.

2013-01-01

The bilateral supplementary comparison APMP.M.P-S4 on pressure measurements in the range (60 to 350) kPa of gauge pressure in gas media was organized by National Institute of Metrology of Thailand, NIMT, as the pilot laboratory, comparing with Physikalisch-Technische Bundesanstalt of Germany, PTB. The objective of this comparison is to check equivalence of gas pressure standards between NIMT and PTB. The period of measurement covered November to December 2012. NIMT provided a transfer standard, which was a WC-WC piston-cylinder assembly (PCA) with a nominal effective area of 10 cm2 manufactured by Fluke Corporation, DHI. The measurements were performed at pressures (60, 100, 150, 200, 250, 300 and 350) kPa. The NIMT laboratory standard used was a pressure balance with a PCA of 10 cm2 manufactured by DHI and identified by serial number 0693. The PTB laboratory standard used was a pressure balance with a PCA of 10 cm2 manufactured by Desgranges et Huot (DH) and identified by serial number 288. The results of this comparison show that the relative difference of the effective area values obtained by NIMT and PTB is not larger than 4.3 ppm, which corresponds to En = 0.26. Therefore, it confirms that the gas pressure standards maintained by the two institutes, NIMT and PTB, in the pressure range (60 to 350) kPa in gauge mode are equivalent under their uncertainties claimed. The result of this comparison is essential to support the calibration and measurement capabilities (CMC) of NIMT in this pressure range. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the APMP, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

[Analysis of the numbers and subsets of MTB-HAg specific TNF-α+ γδ T cells in peripheral blood of patients with active pulmonary tuberculosis].

PubMed

Tang, Jie; Chen, Ce; Zha, Cheng; Wang, Zhaohua; Zhang, Chen; Zeng, Linli; Li, Baiqing

2016-11-01

Objective To investigate the differences of proportions of tumor necrosis factor α (TNF-α)-producing cells in peripheral blood γδ T cells stimulated with Mycobacterium tuberculosis heat resistant antigen (MTB-HAg) among patients with pulmonary tuberculosis (PTB), latent tuberculosis infection (LTBI) and healthy subjects (HC). Methods The peripheral blood specimens were collected from 15 normal adults, which were divided into HC group (n=9) and LTBI group (n=6), by enzyme-linked immunospot (ELISPOT) kit for diagnosis of Mycobacterium tuberculosis infection, and 12 patients with active PTB. The peripheral blood mononuclear cells (PBMCs) were separated by density gradient centrifugation and simulated with MTB-HAg for 20 hours. Then the cells were collected, and the proportions of TNF-α-producing cells in TCRαβ + T cells, TCRγδ + T cells, CD4 + αβ T cells, CD8 + αβ T cells, and TCR-Vδ2 + T cells were measured with flow cytometry. Results The proportion of TNF-α-producing cells in γδ T cells in patients with PTB was obviously lower than that in LTBI group and HC group; the proportion of TNF-α-producing cells in Vδ2 T cells in PTB patients was apparently lower than that in LTBI and HC; the proportion of Vδ2 T cells in TNF-α + γδ T cells in the peripheral blood of PTB patients was remarkably lower than that in LTBI and HC groups. The proportions of TNF-α-producing cells in peripheral αβ T cells, CD4 + and CD8 + αβ T cells were dramatically lower than those in γδ T cells of the three according groups. Moreover, there were no statistical differences in regard with the proportions of TNF-α-producing cells in αβ T cells, and CD4 + and CD8 + αβ T cells among the three groups. Conclusion The TNF-α production capacity of MTB-HAg specific γδ T cells and Vδ2 T cell subsets in patients with tuberculosis is obviously lower than that of LTBI and HC.

A flexible Bayesian hierarchical model of preterm birth risk among US Hispanic subgroups in relation to maternal nativity and education

PubMed Central

2011-01-01

Background Previous research has documented heterogeneity in the effects of maternal education on adverse birth outcomes by nativity and Hispanic subgroup in the United States. In this article, we considered the risk of preterm birth (PTB) using 9 years of vital statistics birth data from New York City. We employed finer categorizations of exposure than used previously and estimated the risk dose-response across the range of education by nativity and ethnicity. Methods Using Bayesian random effects logistic regression models with restricted quadratic spline terms for years of completed maternal education, we calculated and plotted the estimated posterior probabilities of PTB (gestational age < 37 weeks) for each year of education by ethnic and nativity subgroups adjusted for only maternal age, as well as with more extensive covariate adjustments. We then estimated the posterior risk difference between native and foreign born mothers by ethnicity over the continuous range of education exposures. Results The risk of PTB varied substantially by education, nativity and ethnicity. Native born groups showed higher absolute risk of PTB and declining risk associated with higher levels of education beyond about 10 years, as did foreign-born Puerto Ricans. For most other foreign born groups, however, risk of PTB was flatter across the education range. For Mexicans, Central Americans, Dominicans, South Americans and "Others", the protective effect of foreign birth diminished progressively across the educational range. Only for Puerto Ricans was there no nativity advantage for the foreign born, although small numbers of foreign born Cubans limited precision of estimates for that group. Conclusions Using flexible Bayesian regression models with random effects allowed us to estimate absolute risks without strong modeling assumptions. Risk comparisons for any sub-groups at any exposure level were simple to calculate. Shrinkage of posterior estimates through the use of random effects allowed for finer categorization of exposures without restricting joint effects to follow a fixed parametric scale. Although foreign born Hispanic women with the least education appeared to generally have low risk, this seems likely to be a marker for unmeasured environmental and behavioral factors, rather than a causally protective effect of low education itself. PMID:21504612

A flexible Bayesian hierarchical model of preterm birth risk among US Hispanic subgroups in relation to maternal nativity and education.

PubMed

Kaufman, Jay S; MacLehose, Richard F; Torrone, Elizabeth A; Savitz, David A

2011-04-19

Previous research has documented heterogeneity in the effects of maternal education on adverse birth outcomes by nativity and Hispanic subgroup in the United States. In this article, we considered the risk of preterm birth (PTB) using 9 years of vital statistics birth data from New York City. We employed finer categorizations of exposure than used previously and estimated the risk dose-response across the range of education by nativity and ethnicity. Using Bayesian random effects logistic regression models with restricted quadratic spline terms for years of completed maternal education, we calculated and plotted the estimated posterior probabilities of PTB (gestational age < 37 weeks) for each year of education by ethnic and nativity subgroups adjusted for only maternal age, as well as with more extensive covariate adjustments. We then estimated the posterior risk difference between native and foreign born mothers by ethnicity over the continuous range of education exposures. The risk of PTB varied substantially by education, nativity and ethnicity. Native born groups showed higher absolute risk of PTB and declining risk associated with higher levels of education beyond about 10 years, as did foreign-born Puerto Ricans. For most other foreign born groups, however, risk of PTB was flatter across the education range. For Mexicans, Central Americans, Dominicans, South Americans and "Others", the protective effect of foreign birth diminished progressively across the educational range. Only for Puerto Ricans was there no nativity advantage for the foreign born, although small numbers of foreign born Cubans limited precision of estimates for that group. Using flexible Bayesian regression models with random effects allowed us to estimate absolute risks without strong modeling assumptions. Risk comparisons for any sub-groups at any exposure level were simple to calculate. Shrinkage of posterior estimates through the use of random effects allowed for finer categorization of exposures without restricting joint effects to follow a fixed parametric scale. Although foreign born Hispanic women with the least education appeared to generally have low risk, this seems likely to be a marker for unmeasured environmental and behavioral factors, rather than a causally protective effect of low education itself.

Maternal vitamin D insufficiency and risk of adverse pregnancy and birth outcomes: A systematic review and meta-analysis of longitudinal studies

PubMed Central

Klevor, Moses K.; Wagner, Carol L.

2017-01-01

Background Three previous reviews on the association of vitamin D insufficiency in pregnancy with preterm birth (PTB) and stillbirth were limited in scope and deemed inconclusive. With important new evidence accumulating, there is the need to update the previous estimates and assess evidence on other clinically important outcomes such as spontaneous abortion and Apgar score. We conducted a systematic review and meta-analysis to evaluate the quality and strength of the available evidence on the relations between vitamin D nutritional status, and pregnancy and birth outcomes. Methods PubMed and Scopus databases were searched from their inception to June, 2015 with no language restrictions imposed. Eighteen longitudinal studies satisfied the inclusion criteria. Random effects model was applied in computing the summary effect estimates and their corresponding 95% confidence intervals. Results Serum 25(OH)D levels <75 nmol/l was associated with 83% (95% CI: 1.23, 2.74) and 13% (95% CI: 0.94, 1.36) increased risk of PTB measured at <32–34 weeks and <35–37 weeks, respectively. An inverse dose-response relation was observed for both PTB outcome. Serum 25(OH)D levels <75 nmol/l was also associated with 11% increased risk of spontaneous PTB (<35–37 weeks; RR = 1.11; 95% CI: 0.75, 1.65) with a dose-response relation also noted. Vitamin D insufficiency was not associated with risk of spontaneous abortion and stillbirth (RR of 1.04 [95% CI: 0.95, 1.13] and 1.02 [95% CI: 0.96, 1.09], respectively), as well as short gestational length (ES = -0.24, 95% CI: -0.69, 0.22), and low Apgar score. Conclusions We found vitamin D insufficiency to be associated with risk of PTB. Regarding spontaneous abortion and stillbirth, the available evidence suggest no association with low vitamin D levels. The evidence on vitamin D nutrition and Apgar score is conflicting and controversial. Overall, the experimental evidence uncovered was small and weak. Hence, the benefits of vitamin D supplementation during pregnancy should be further evaluated through rigorous intervention studies. PMID:28306725

Maternal vitamin D insufficiency and risk of adverse pregnancy and birth outcomes: A systematic review and meta-analysis of longitudinal studies.

PubMed

Amegah, A Kofi; Klevor, Moses K; Wagner, Carol L

2017-01-01

Three previous reviews on the association of vitamin D insufficiency in pregnancy with preterm birth (PTB) and stillbirth were limited in scope and deemed inconclusive. With important new evidence accumulating, there is the need to update the previous estimates and assess evidence on other clinically important outcomes such as spontaneous abortion and Apgar score. We conducted a systematic review and meta-analysis to evaluate the quality and strength of the available evidence on the relations between vitamin D nutritional status, and pregnancy and birth outcomes. PubMed and Scopus databases were searched from their inception to June, 2015 with no language restrictions imposed. Eighteen longitudinal studies satisfied the inclusion criteria. Random effects model was applied in computing the summary effect estimates and their corresponding 95% confidence intervals. Serum 25(OH)D levels <75 nmol/l was associated with 83% (95% CI: 1.23, 2.74) and 13% (95% CI: 0.94, 1.36) increased risk of PTB measured at <32-34 weeks and <35-37 weeks, respectively. An inverse dose-response relation was observed for both PTB outcome. Serum 25(OH)D levels <75 nmol/l was also associated with 11% increased risk of spontaneous PTB (<35-37 weeks; RR = 1.11; 95% CI: 0.75, 1.65) with a dose-response relation also noted. Vitamin D insufficiency was not associated with risk of spontaneous abortion and stillbirth (RR of 1.04 [95% CI: 0.95, 1.13] and 1.02 [95% CI: 0.96, 1.09], respectively), as well as short gestational length (ES = -0.24, 95% CI: -0.69, 0.22), and low Apgar score. We found vitamin D insufficiency to be associated with risk of PTB. Regarding spontaneous abortion and stillbirth, the available evidence suggest no association with low vitamin D levels. The evidence on vitamin D nutrition and Apgar score is conflicting and controversial. Overall, the experimental evidence uncovered was small and weak. Hence, the benefits of vitamin D supplementation during pregnancy should be further evaluated through rigorous intervention studies.

Long-Term Effects of a Randomised Controlled Trial Comparing High Protein or High Carbohydrate Weight Loss Diets on Testosterone, SHBG, Erectile and Urinary Function in Overweight and Obese Men

PubMed Central

Moran, Lisa J.; Brinkworth, Grant D.; Martin, Sean; Wycherley, Thomas P.; Stuckey, Bronwyn; Lutze, Janna; Clifton, Peter M.; Wittert, Gary A.; Noakes, Manny

2016-01-01

Introduction Obesity is associated with reduced testosterone and worsened erectile and sexual function in men. Weight loss improves these outcomes. High protein diets potentially offer anthropometric and metabolic benefits, but their effects on reproductive and sexual outcomes is not known. Aim To examine the long-term effects of weight loss with a higher protein or carbohydrate diet on testosterone, sex hormone binding globulin, erectile dysfunction, lower urinary tract symptoms and sexual desire in overweight and obese men. Methods One-hundred and eighteen overweight or obese men (body mass index 27–40 kg/m2, age 20–65 years) were randomly assigned to an energy restricted higher protein low fat (35% protein, 40% carbohydrate, 25% fat; n = 57) or higher carbohydrate low fat diet (17% protein, 58% carbohydrate, 25% fat, n = 61) diet for 52 weeks (12 weeks weight loss, 40 weeks weight maintenance). Primary outcomes were serum total testosterone, sex hormone binding globulin and calculated free testosterone. Secondary outcomes were erectile function as assessed by the International Index of Erectile Function (IIEF) (total score and erectile function domain), lower urinary tract symptoms and sexual desire. Results Total testosterone, sex hormone binding globulin and free testosterone increased (P<0.001) and the total IIEF increased (P = 0.017) with no differences between diets (P≥0.244). Increases in testosterone (P = 0.037) and sex hormone binding globulin (P<0.001) and improvements in the total IIEF (P = 0.041) occurred from weeks 0–12 with a further increase in testosterone from week 12–52 (P = 0.002). Increases in free testosterone occurred from week 12–52 (p = 0.002). The IIEF erectile functon domain, lower urinary tract symptoms and sexual desire did not change in either group (P≥0.126). Conclusions In overweight and obese men, weight loss with both high protein and carbohydrate diets improve testosterone, sex hormone binding globulin and overall sexual function. Trial Registration Anzctr.org.au ACTRN12606000002583 PMID:27584019

Antibody-Based Therapy for Enterococcal Catheter-Associated Urinary Tract Infections.

PubMed

Flores-Mireles, Ana L; Walker, Jennifer N; Potretzke, Aaron; Schreiber, Henry L; Pinkner, Jerome S; Bauman, Tyler M; Park, Alyssa M; Desai, Alana; Hultgren, Scott J; Caparon, Michael G

2016-10-25

Gram-positive bacteria in the genus Enterococcus are a frequent cause of catheter-associated urinary tract infection (CAUTI), a disease whose treatment is increasingly challenged by multiantibiotic-resistant strains. We have recently shown that E. faecalis uses the Ebp pilus, a heteropolymeric surface fiber, to bind the host protein fibrinogen as a critical step in CAUTI pathogenesis. Fibrinogen is deposited on catheters due to catheter-induced inflammation and is recognized by the N-terminal domain of EbpA (EbpA NTD ), the Ebp pilus's adhesin. In a murine model, vaccination with EbpA NTD confers significant protection against CAUTI. Here, we explored the mechanism of protection using passive transfer of immune sera to show that antisera blocking EbpA NTD -fibrinogen interactions not only is prophylactic but also can act therapeutically to reduce bacterial titers of an existing infection. Analysis of 55 clinical CAUTI, bloodstream, and gastrointestinal isolates, including E. faecalis, E. faecium, and vancomycin-resistant enterococci (VRE), revealed a diversity of levels of EbpA expression and fibrinogen-binding efficiency in vitro Strikingly, analysis of 10 strains representative of fibrinogen-binding diversity demonstrated that, irrespective of EbpA levels, EbpA NTD antibodies were universally protective. The results indicate that, despite diversity in levels of fibrinogen binding, strategies that target the disruption of EbpA NTD -fibrinogen interactions have considerable promise for treatment of CAUTI. Urinary catheterization is a routine medical procedure, and it has been estimated that 30 million Foley catheters are used annually in the United States. Importantly, placement of a urinary catheter renders the patient susceptible to developing a catheter-associated urinary tract infection, accounting for 1 million cases per year. Additionally, these infections can lead to serious complications, including bloodstream infection and death. Enterococcus strains are a common cause of these infections, and management of enterococcal infections has been more difficult in recent years due to the development of antibiotic resistance and the ability of strains to disseminate, resulting in a major threat in hospital settings. In this study, we developed an antibiotic-sparing treatment that is effective against diverse enterococcal isolates, including vancomycin-resistant enterococci, during catheter-associated urinary tract infections. Copyright © 2016 Flores-Mireles et al.

Effect of power toothbrushing on simulated wear of dental cement margins.

PubMed

Black, Marsha A; Bayne, Stephen C; Peterson, Charlotte A

2007-01-01

Power toothbrushes (PTBs), in combination with abrasive dentifrices, may encourage wear of dental cements at crown margins. The objective of this in vitro simulation was to control the clinical variables associated with PTB use and measure the potential side effects of PTBs with mild and abrasive dentifrices. Four PTBs ( Braun-Oral-B-Professional Care at 150 g brushing force, Sonicare-Elite at 90 g, Colgate-Actibrush at 200 g and Crest-Spinbrush-Pro at 250 g) and 2 dentifrices mixed 1:1 with tap water (Mild= Colgate-Total, Colgate-Palmolive; Abrasive= Close-up, Chesebrough-Ponds) versus tap water alone (control) were used to abrade 2 cements (Fleck's Mizzy Zinc Phosphate [ZP]; 3M-ESPE Unicem universal cement [UC]) using cement-filled slots (160 m wide) cut into wear-resistant ceramic blocks. A custom fixture controlled PTB/block alignment, PTB loads, and other testing variables. Wear was measured (3 profilometer traces/slot, 5 slots/block/group, baseline to 5-year differences) and analyzed (3-way ANOVA, p < or = 0.05, Bonferroni). Wear for ZP was much greater than UC (p<0.05) for all 4 PTBs and both dentifrices. Brushing with water showed no effects (p<0.05). Cement-PTB-dentifrice interactions did occur. Only minor differences occurred among PTBs. Pooled 5y-wear levels for ZP for both dentifrices approximately 21 microm /5y) were similar to values for current-day posterior composite materials. Combinations of PTBs with mild and abrasive dentifrices produced significant wear with ZP but not UC; thus, resin-composite cements seem to represent a better choice for wear resistance.

Disparities in Maternal Child and Health Outcomes Attributable to Prenatal Tobacco Use

PubMed Central

Mohlman, Mary Katherine; Levy, David T.

2015-01-01

Objectives Previous estimates of smoking-attributable adverse outcomes, such as preterm births (PTBs), low birth weight (LBW) and Sudden Infant Death Syndrome (SIDs) generally do not address disparities by maternal age, racial/ethnic group or socioeconomic status (SES). This study develops estimates of smoking-attributable PTB, LBW and SIDS for the US by age, SES and racial/ethnic groupings. Methods Data on the number of births and the prevalence of PTB, LBW and SIDS were used to develop the number of outcomes by age, race/ethnicity, and SES. The prevalence of prenatal smoking by age, race/ethnic and education and the relative risk of outcomes for smokers were used to calculate smoking-attributable fractions of outcomes. Results Prenatal smoking among ages 15-24 is above 12%, with 20-24 year olds representing at least 35% of PTB, LBW SIDS cases. Women with a high school education or less represented more than 50% of PTB and LBW births, and 44% of SIDS cases. While non-Hispanic Whites had the majority of smoking-attributable outcomes, non-Hispanic Blacks represented a disproportionately high percentage of PTBs (18%), LBW births (22%), and SIDS cases (13%). Conclusions: Reducing prenatal smoking has the potential to reduce adverse birth outcomes and costs with long-term implications, especially among the young, non-Hispanic Blacks and those of lower SES. Stricter tobacco control policies, especially higher cigarette taxes, higher minimum purchase ages for tobacco and improved cessation interventions can help reduce disparities and the cost to insurers, especially public costs through Medicaid. PMID:26645613

Transcriptome signature identifies distinct cervical pathways induced in lipopolysaccharide-mediated preterm birth.

PubMed

Willcockson, Alexandra R; Nandu, Tulip; Liu, Cheuk-Lun; Nallasamy, Shanmugasundaram; Kraus, W Lee; Mahendroo, Mala

2018-03-01

With half a million babies born preterm each year in the USA and about 15 million worldwide, preterm birth (PTB) remains a global health issue. Preterm birth is a primary cause of infant morbidity and mortality and can impact lives long past infancy. The fact that there are numerous, and many currently unidentified, etiologies of PTB has hindered development of tools for risk evaluation and preventative therapies. Infection is estimated to be involved in nearly 40% of PTBs of known etiology; therefore, understanding how infection-mediated inflammation alters the cervical milieu and leads to preterm tissue biomechanical changes are questions of interest. Using RNA-seq, we identified enrichment of components involved in inflammasome activation and unique proteases in the mouse cervix during lipopolysaccharide (LPS)-mediated PTB and not physiologically at term before labor. Despite transcriptional induction of inflammasome components, there was no evidence of functional activation based on assessment of mature IL1B and IL18 proteins. The increased transcription of proteases that target both elastic fibers and collagen and concentration of myeloid-derived cells capable of protease synthesis in the cervical stroma support the structural disruption of elastic fibers as a functional output of protease activity. The recent demonstration that elastic fibers contribute to the biomechanical function of the pregnant cervix suggests their protease-induced disruption in the infection model of LPS-mediated PTB and may contribute to premature loss of mechanical competency and preterm delivery. Collectively, the transcriptomics and ultrastructural data provide new insights into the distinct mechanisms of premature cervical remodeling in response to infection.

The impact of postpartum cervical tear on the occurrence of preterm birth in subsequent pregnancy.

PubMed

Zafran, Noah; Gerszman, Eden; Garmi, Gali; Zuaretz-Easton, Sivan; Salim, Raed

2017-08-01

To examine the occurrence of subsequent preterm birth (PTB) among women who experienced a cervical tear during prior delivery. A retrospective study conducted at a single teaching hospital on data from January 1994 to March 2014. The study group included all women who had a cervical tear detected at uterine and cervical examination, performed due to early postpartum hemorrhage. The control group consisted of women who delivered vaginally, experienced an early postpartum hemorrhage, and had an intact cervix at uterine and cervical examination. The control group was matched for maternal age and ethnicity at a ratio of 1:2. Women who had a cervical tear but then did not have a subsequent delivery, or had multiple fetal gestations or cervical cerclage at subsequent pregnancies were excluded. Primary outcome was spontaneous PTB rate (<37 weeks) in the subsequent pregnancy. Secondary outcomes included any PTBs in other subsequent pregnancies. Overall, 389 women were included. Of all cases of cervical tear, 129 were identified eligible and included in the final analysis. The control group included 260 women with an intact cervix. No significant differences were found between the study and control groups in the incidence of spontaneous PTB in the immediate subsequent pregnancy [1.6% (2/129) vs. 3.8% (10/260), respectively, p = 0.35]. The incidence of any spontaneous PTBs in all subsequent pregnancies did not differ also [4.7% (6/129) vs. 7.3% (19/260), respectively, p = 0.31]. Cervical tear detected after delivery does not increase the risk of spontaneous PTB in subsequent pregnancies.

Epstein-Barr virus-induced gene 3 (EBI3) polymorphisms and expression are associated with susceptibility to pulmonary tuberculosis.

PubMed

Zheng, Ruijuan; Liu, Haipeng; Song, Peng; Feng, Yonghong; Qin, Lianhua; Huang, Xiaochen; Chen, Jianxia; Yang, Hua; Liu, Zhonghua; Cui, Zhenglin; Hu, Zhongyi; Ge, Baoxue

2015-07-01

Tuberculosis (TB) remains a major global health problem and host genetic factors play a critical role in susceptibility and resistance to TB. The aim of this study was to identify novel candidate genes associated with TB susceptibility. We performed a population-based case-control study to genotype 13 tag SNPs spanning Epstein-Barr virus-induced gene 3 (EBI3), colony stimulating factor 2 (CSF2), IL-4, interferon beta 1 (IFNB1), chemokine (C-X-C motif) ligand 14 (CXCL14) and myeloid differentiation primary response gene 88 (Myd88) genes in 435 pulmonary TB patients and 375 health donors from China. We observed that EBI3 gene rs4740 polymorphism was associated with susceptibility to pulmonary tuberculosis (PTB) and the allele G was associated with a protective effect against PTB. Furthermore, EBI3 deficiency led to reduced bacterial burden and histopathological impairment in the lung of mice infected with Mycobacterium bovis BCG. Meanwhile, higher abundance of EBI3 was observed in the granuloma of PTB patients and in the lung tissue of BCG-infected mice. Of note, the expression of EBI3 in macrophages was remarkably induced by mycobacteria infection at both mRNA and protein level. In conclusion, EBI3 gene rs4740 polymorphism is closely associated with susceptibility to PTB and the elevation and enrichment of EBI3 in the lung which at least partially derived from macrophages may contribute to the exacerbation of mycobacterial infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low-Density Granulocytes Are Elevated in Mycobacterial Infection and Associated with the Severity of Tuberculosis

PubMed Central

Luo, Qing; Huang, Zhikun; Peng, Yiping; Xiong, Guoliang; Guo, Yang; Jiang, Hong; Li, Junming

2016-01-01

Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis. PMID:27073889

Do transportation subsidies and living allowances improve tuberculosis control outcomes among internal migrants in urban Shanghai, China?

PubMed

Lu, Hui; Yan, Fei; Wang, Wei; Wu, Laiwa; Ma, Weiping; Chen, Jing; Shen, Xin; Mei, Jian

2013-01-01

Tuberculosis (TB) in internal migrants is one of three threats for TB control in China. To address this threat, a project was launched in eight of the 19 districts of Shanghai in 2007 to provide transportation subsidies and living allowances for all migrant TB cases. This study aims to determine if this project contributed to improved TB control outcomes among migrants in urban Shanghai. This was a community intervention study. The data were derived from the TB Management Information System in three project districts and three non-project districts in Shanghai between 2006 and 2010. The impact of the project was estimated in a difference-in-difference (DID) analysis framework, and a multivariable binary logistic regression analysis. A total of 1872 pulmonary TB (PTB) cases in internal migrants were included in the study. The treatment success rate (TSR) for migrant smear-positive cases in project districts increased from 59.9% in 2006 to 87.6% in 2010 (P < 0.001). The crude DID improvement of TSR was 18.9%. There was an increased probability of TSR in the project group before and after the project intervention period (coefficient = 1.156, odds ratio = 3.178, 95% confidence interval: 1.305-7.736, P = 0.011). The study showed the project could improve treatment success in migrant PTB cases. This was a short-term programme using special financial subsidies for all migrant PTB cases. It is recommended that project funds be continuously invested by governments with particular focus on the more vulnerable PTB cases among migrants.

Iloprost improves ventricular function in the hypertrophic and functionally impaired right heart by direct stimulation.

PubMed

Holmboe, Sarah; Andersen, Asger; Vildbrad, Mads D; Nielsen, Jan M; Ringgaard, Steffen; Nielsen-Kudsk, Jens E

2013-12-01

Right heart function is an important predictor of morbidity and mortality in patients suffering from pulmonary arterial hypertension and congenital heart diseases. We investigated whether the prostacyclin analog iloprost has a direct inotropic effect in the pressure-overloaded hypertrophic and dysfunctional right ventricle (RV). Rats were randomized to monocrotaline injection (60 mg/kg; [Formula: see text]), pulmonary trunk banding (PTB; [Formula: see text]), or a sham operation ([Formula: see text]). RV function was evaluated with magnetic resonance imaging, echocardiography, and invasive pressure measurements at baseline, after intravenous administration of placebo, iloprost 10 ng/kg/min, or iloprost 100 ng/kg/min (Ilo100). Infusion of Ilo100 induced a [Formula: see text] ([Formula: see text]) increase in stroke volume in the sham group and a [Formula: see text] ([Formula: see text]) increase in the PTB group. RV [Formula: see text] was elevated by [Formula: see text] ([Formula: see text]) in the sham group and by [Formula: see text] ([Formula: see text]) in the PTB group. An elevation in cardiac output of [Formula: see text] ([Formula: see text]) and an [Formula: see text] ([Formula: see text]) increase in RV systolic pressure were found in the PTB group. Iloprost caused a decrease in mean arterial blood pressure (MAP) in all groups of animals. An equal reduction in MAP induced by the arterial vasodilator nitroprusside did not improve any of the measured parameters of RV function. We conclude that iloprost has inotropic properties directly improving ventricular function in the hypertrophic and dysfunctional right heart of the rat.

Role of maternal occupational physical activity and psychosocial stressors on adverse birth outcomes

PubMed Central

Lee, Laura J; Symanski, Elaine; Lupo, Philip J; Tinker, Sarah C; Razzaghi, Hilda; Chan, Wenyaw; Hoyt, Adrienne T; Canfield, Mark A

2016-01-01

Objectives We examined the association of an array of estimated maternal occupational physical activities and psychosocial stressors during pregnancy with odds for preterm birth (PTB) and small-for-gestational age (SGA). Methods Data for infants born without major birth defects delivered from 1997 to 2009 whose mothers reported working at least 1 month during pregnancy were obtained from the National Birth Defects Prevention Study. We linked occupational codes to the US Department of Labor’s Occupational Information Network, which provides estimates of exposure for multiple domains of physical activity and psychosocial stressors by occupational categories. We conducted factor analysis using principal components extraction with 17 occupational activities and calculated factor scores. ORs for PTB and SGA across quartiles of factor scores in each trimester were computed using logistic regression. Results Factor analysis grouped occupational domains into 4 groups based on factor loadings. These groups were ‘occupational physical activity’, ‘interpersonal stressor’, ‘automated work’ and ‘job responsibility’. High levels of ‘occupational physical activity’ were significantly associated with SGA (adjusted OR (AOR) for highest quartile compared with lowest quartile of factor score: 1.36; 95% CIs 1.02 to 1.82; p for trend=0.001) and were also positively associated with PTB (AOR: 1.24; 95% CI 0.93 to 1.64; p for trend=0.01). No clear results were observed across domains of psychosocial stressors. Conclusions Our findings expand understanding of associations between occupational physical activity and psychosocial stressors and PTB and SGA and suggest that additional research is needed to further examine these relationships. PMID:27919059

Final report on COOMET.EM-S11: Supplementary bilateral comparison of the measurement of current transformers between UNIIM and PTB

NASA Astrophysics Data System (ADS)

Mohns, Enrico; Sychev, Y.; Roeissle, G.

2014-01-01

A bilateral comparison of the measurement of current transformers was carried out between UNIIM (Russia) and PTB (Germany). For all of the current ratio error measurements and the phase displacement measurements there is a close agreement between PTB and UNIIM. Extensive measurements with the travelling standards were carried out at 18 different current ratios and at 5 different test points (1%, 5%, 20%, 100% and 120%) each. The range of tested primary currents was from 10 mA to 60 kA. It can therefore be concluded that the results of each laboratory agree very well within the calculated measurement uncertainties. No outliers were observed. Considering especially the En factors, the calculated uncertainties seem to be too conservative to some extent. Here there is the possibility to slightly improve the uncertainty budgets in the future if there is a need. The worst En factors are within ±0.6 at 1 kA/5 A and ±0.8 at 3 kA. The current comparator 'IW 32' from PTB may have caused that. This was subsequently confirmed. The primary current induced a small voltage in the compensation winding. This problem has now been solved. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospital-based retrospective study

PubMed Central

Sreeramareddy, Chandrashekhar T; Panduru, Kishore V; Verma, Sharat C; Joshi, Hari S; Bates, Michael N

2008-01-01

Background Studies from developed countries have reported on host-related risk factors for extra-pulmonary tuberculosis (EPTB). However, similar studies from high-burden countries like Nepal are lacking. Therefore, we carried out this study to compare demographic, life-style and clinical characteristics between EPTB and PTB patients. Methods A retrospective analysis was carried out on 474 Tuberculosis (TB) patients diagnosed in a tertiary care hospital in western Nepal. Characteristics of demography, life-style and clinical features were obtained from medical case records. Risk factors for being an EPTB patient relative to a PTB patient were identified using logistic regression analysis. Results The age distribution of the TB patients had a bimodal distribution. The male to female ratio for PTB was 2.29. EPTB was more common at younger ages (< 25 years) and in females. Common sites for EPTB were lymph nodes (42.6%) and peritoneum and/or intestines (14.8%). By logistic regression analysis, age less than 25 years (OR 2.11 95% CI 1.12–3.68) and female gender (OR 1.69, 95% CI 1.12–2.56) were associated with EPTB. Smoking, use of immunosuppressive drugs/steroids, diabetes and past history of TB were more likely to be associated with PTB. Conclusion Results suggest that younger age and female gender may be independent risk factors for EPTB in a high-burden country like Nepal. TB control programmes may target young and female populations for EPTB case-finding. Further studies are necessary in other high-burden countries to confirm our findings. PMID:18218115

Trace elements in blood samples of smoker and nonsmoker active pulmonary tuberculosis patients from Jamshoro, Pakistan.

PubMed

Memon, Zainab Manzoor; Yilmaz, Erkan; Shah, Afsheen Mushtaque; Sahin, Ugur; Kazi, Tasneem Gul; Devrajani, Bikha Ram; Soylak, Mustafa

2017-12-01

Pulmonary tuberculosis (PTB) is a serious public threat throughout the world. PTB and smoking have a strong correlation. Malnutrition, poverty, addiction, overcrowding, illiteracy, unemployment, and poor hygienic conditions are the collective aspects for the disease progress. Pakistan is the fifth among 22 high tuberculosis (TB) burden countries and the fourth regarding multidrug-resistant tuberculosis (MDR-TB). The aim of study was to determine the concentration of essential and toxic elements from blood samples of smoker and nonsmoker PTB patients by inductively coupled plasma mass spectrometry (ICP-MS) followed by microwave acid digestion and compared with control subjects (n = 30). Eighty PTB patients were selected from different hospitals with age ranging 20-70 years. It was interpreted that the mean age among males and females was found to be 35.6 ± 1.4 and 33.5 ± 1.2, respectively, and the male patients were highly affected in contrast to females. Essential elements such as Mn, Fe, Zn, and Se were statistically found to be lower while Ca, Co, and Cu were found to be higher compared to the control group (p = 0.00). However, toxic elements like Al, Cr, Ni, As, Cd, and Pb were statistically elevated in smokers than nonsmokers. Further research is needed to understand the degree of the impact of essential trace elements on treatment outcome (follow-up) followed by balanced healthy nutritional supplementation along with medical therapy, consequently improving the pulmonary tuberculosis outcome and survival as well.

A screening system for smear-negative pulmonary tuberculosis using artificial neural networks.

PubMed

de O Souza Filho, João B; de Seixas, José Manoel; Galliez, Rafael; de Bragança Pereira, Basilio; de Q Mello, Fernanda C; Dos Santos, Alcione Miranda; Kritski, Afranio Lineu

2016-08-01

Molecular tests show low sensitivity for smear-negative pulmonary tuberculosis (PTB). A screening and risk assessment system for smear-negative PTB using artificial neural networks (ANNs) based on patient signs and symptoms is proposed. The prognostic and risk assessment models exploit a multilayer perceptron (MLP) and inspired adaptive resonance theory (iART) network. Model development considered data from 136 patients with suspected smear-negative PTB in a general hospital. MLP showed higher sensitivity (100%, 95% confidence interval (CI) 78-100%) than the other techniques, such as support vector machine (SVM) linear (86%; 95% CI 60-96%), multivariate logistic regression (MLR) (79%; 95% CI 53-93%), and classification and regression tree (CART) (71%; 95% CI 45-88%). MLR showed a slightly higher specificity (85%; 95% CI 59-96%) than MLP (80%; 95% CI 54-93%), SVM linear (75%, 95% CI 49-90%), and CART (65%; 95% CI 39-84%). In terms of the area under the receiver operating characteristic curve (AUC), the MLP model exhibited a higher value (0.918, 95% CI 0.824-1.000) than the SVM linear (0.796, 95% CI 0.651-0.970) and MLR (0.782, 95% CI 0.663-0.960) models. The significant signs and symptoms identified in risk groups are coherent with clinical practice. In settings with a high prevalence of smear-negative PTB, the system can be useful for screening and also to aid clinical practice in expediting complementary tests for higher risk patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Gentrification and preterm birth in New York City, 2008–2010.

PubMed

Huynh, M; Maroko, A R

2014-02-01

Adverse birth outcomes have been linked to neighborhood level socioeconomic status. However, little work has examined the influence of social and economic change over time (i.e., gentrification) on health. This study aims to assess the association between gentrification and preterm birth (PTB) while examining the modifying effect of maternal race/ethnicity and educational attainment. New York City births, 2008–2010, (n=126,165) were linked to a measure of gentrification at the community district level (n=59). The gentrification measure was calculated using percent change in education level, poverty level, and median household income (MHI) between the 2005–2009 American Community Survey and the 1990 Census. PTB was defined as clinical gestational age less than 37 weeks. Generalized estimating equations were utilized to examine the association. Gentrification (i.e., increase in residents with a college education, increase in MHI, and decrease in residents living below the poverty line) was not associated with PTB. However, among Non-Hispanic Blacks, very high gentrification was adversely associated with PTB (AOR, 1.16; 95 % CI, 1.01–1.33) as compared to those who lived in a very low gentrified neighborhood. Among non- Hispanic Whites, living in a very high gentrified neighborhood was protective as compared to living in a very low gentrified neighborhood (AOR, 0.78; 95 % CI, 0.64– 0.94). Although there is a need to develop a more nuanced measure of gentrification, these results indicate that changes in the economic character of a neighborhood may have a significant influence on birth outcomes.

Pharmacokinetics of Antiretrovirals in Mucosal Tissue

PubMed Central

Cottrell, M.L.; Srinivas, N.; Kashuba, A.D.M.

2015-01-01

Introduction In the absence of an HIV vaccine or cure, antiretroviral (ARV) based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site HIV exposure which is most commonly the mucosal tissues of the lower gastrointestinal tract and the female genital tract. Areas covered This article collates all known data regarding drug exposure in these vulnerable mucosal tissues, and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing antiretroviral pharmacokinetics in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport, and endogenous hormones, are also reviewed. Expert opinion ARVs exhibit highly variable pharmacokinetics in mucosal tissues. In general, antiretroviral exposure is higher in the lower gastrointestinal tract compared to the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing antiretroviral based prevention strategies. PMID:25797064

Glycomic Characterization of Respiratory Tract Tissues of Ferrets

PubMed Central

Jia, Nan; Barclay, Wendy S.; Roberts, Kim; Yen, Hui-Ling; Chan, Renee W. Y.; Lam, Alfred K. Y.; Air, Gillian; Peiris, J. S. Malik; Dell, Anne; Nicholls, John M.; Haslam, Stuart M.

2014-01-01

The initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid-terminated glycoconjugates on the host cell surface. The sialic acid residues can be linked to the adjacent monosaccharide by α2–3- or α2–6-type glycosidic bonds. It is this linkage difference that primarily defines the species barrier of the influenza virus infection with α2–3 binding being associated with avian influenza viruses and α2–6 binding being associated with human strains. The ferret has been extensively used as an animal model to study the transmission of influenza. To better understand the validity of this model system, we undertook glycomic characterization of respiratory tissues of ferret, which allows a comparison of potential viral receptors to be made between humans and ferrets. To complement the structural analysis, lectin staining experiments were performed to characterize the regional distributions of glycans along the respiratory tract of ferrets. Finally, the binding between the glycans identified and the hemagglutinins of different strains of influenza viruses was assessed by glycan array experiments. Our data indicated that the respiratory tissues of ferret heterogeneously express both α2–3- and α2–6-linked sialic acids. However, the respiratory tissues of ferret also expressed the Sda epitope (NeuAcα2-3(GalNAcβ1–4)Galβ1–4GlcNAc) and sialylated N,N′-diacetyllactosamine (NeuAcα2–6GalNAcβ1–4GlcNAc), which have not been observed in the human respiratory tract surface epithelium. The presence of the Sda epitope reduces potential binding sites for avian viruses and thus may have implications for the usefulness of the ferret in the study of influenza virus infection. PMID:25135641

Glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies.

PubMed

Jia, Nan; Barclay, Wendy S; Roberts, Kim; Yen, Hui-Ling; Chan, Renee W Y; Lam, Alfred K Y; Air, Gillian; Peiris, J S Malik; Dell, Anne; Nicholls, John M; Haslam, Stuart M

2014-10-10

The initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid-terminated glycoconjugates on the host cell surface. The sialic acid residues can be linked to the adjacent monosaccharide by α2-3- or α2-6-type glycosidic bonds. It is this linkage difference that primarily defines the species barrier of the influenza virus infection with α2-3 binding being associated with avian influenza viruses and α2-6 binding being associated with human strains. The ferret has been extensively used as an animal model to study the transmission of influenza. To better understand the validity of this model system, we undertook glycomic characterization of respiratory tissues of ferret, which allows a comparison of potential viral receptors to be made between humans and ferrets. To complement the structural analysis, lectin staining experiments were performed to characterize the regional distributions of glycans along the respiratory tract of ferrets. Finally, the binding between the glycans identified and the hemagglutinins of different strains of influenza viruses was assessed by glycan array experiments. Our data indicated that the respiratory tissues of ferret heterogeneously express both α2-3- and α2-6-linked sialic acids. However, the respiratory tissues of ferret also expressed the Sda epitope (NeuAcα2-3(GalNAcβ1-4)Galβ1-4GlcNAc) and sialylated N,N'-diacetyllactosamine (NeuAcα2-6GalNAcβ1-4GlcNAc), which have not been observed in the human respiratory tract surface epithelium. The presence of the Sda epitope reduces potential binding sites for avian viruses and thus may have implications for the usefulness of the ferret in the study of influenza virus infection. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Transcriptional profiles discriminate patients with pulmonary tuberculosis from non-tuberculous individuals depending on the presence of non-insulin diabetes mellitus.

PubMed

Serrano, Carmen J; Cuevas-Córdoba, Betzaida; Macías-Segura, Noé; González-Curiel, Rosa Angélica; Martínez-Balderas, Víctor Yordani; Enciso-Moreno, Leonor; Small, Peter; Hernández-Pando, Rogelio; Enciso-Moreno, José Antonio

2016-01-01

Our objective was to identify transcriptional biomarkers in peripheral blood mononuclear cells (PBMC) that discriminate individuals with latent tuberculosis infection (LTBI) from those with pulmonary tuberculosis (PTB) in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in individuals without NIDDM. Using gene expression microarrays we identified differentially expressed genes from lungs of mice infected with Mycobacterium tuberculosis (Mtb) or a mutant (ΔsigH) representing a non-inflammatory model. Genes expressed in blood, with inflammatory related functions were evaluated in humans by RT-qPCR. NCF1 and ORM transcripts have the better discriminatory capacity to identify PTB subjects from LTBI and non-infected controls (NICs) independently of the presence of NIDDM. The sequential evaluation of the mRNA levels of NCF1 and ORM as multiple diagnostic tests showed 95% Sensitivity (Se) and 80% Specificity (Sp). In addition, FPR2 promises to be a good biomarker for the PTB detection in subjects with NIDDM (Se=100%; Sp=90%). Copyright © 2015 Elsevier Inc. All rights reserved.

Explaining Racial Disparities in Infant Health in Brazil

PubMed Central

Nyarko, Kwame A.; Lopez-Camelo, Jorge; Castilla, Eduardo E.

2015-01-01

Objectives. We sought to quantify how socioeconomic, health care, demographic, and geographic effects explain racial disparities in low birth weight (LBW) and preterm birth (PTB) rates in Brazil. Methods. We employed a sample of 8949 infants born between 1995 and 2009 in 15 cities and 7 provinces in Brazil. We focused on disparities in LBW (< 2500 g) and PTB (< 37 gestational weeks) prevalence between infants of African ancestry alone or African mixed with other ancestries, and European ancestry alone. We used a decomposition model to quantify the contributions of conceptually relevant factors to these disparities. Results. The model explained 45% to 94% of LBW and 64% to 94% of PTB disparities between the African ancestry groups and European ancestry. Differences in prenatal care use and geographic location were the most important contributors, followed by socioeconomic differences. The model explained the majority of the disparities for mixed African ancestry and part of the disparity for African ancestry alone. Conclusions. Public policies to improve children’s health should target prenatal care and geographic location differences to reduce health disparities between infants of African and European ancestries in Brazil. PMID:26313046