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Background: The United States has one of the highest maternal mortality rates of developing countries, but the contribution of perinatal drug overdose is not known. Communities of color also have higher rates of maternal morbidity and mortality when compared to White communities, however the contribution due to overdose has not yet been examined in this population., Objectives: To quantify the years of life lost due to unintentional overdose in perinatal individuals from 2010 to 2019 and assess for disparity by race., Study Design: This was a cross-sectional retrospective study with summary-level mortality statistics for the years 2010-2019 obtained from the Centers for Disease Control (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) mortality file. A total of 1,586 individuals of childbearing age (15-44 years) who died during pregnancy or six weeks postpartum (perinatal) from unintentional overdose in the United States from January 1, 2010 to December 31, 2019 were included. Total years of life lost (YLL) was calculated and summated for White, Black, Hispanic, Asian/Pacific Islander, and American Indian/Native Alaska women. Additionally, the top three overall causes of death were also identified for women in this age group for comparison., Results: Unintentional drug overdose accounted for 1,586 deaths and 83,969.78 YLL in perinatal individuals from 2010 to 2019 in the United States. Perinatal American Indian/Native American individuals had a disproportionate amount of YLL when compared to other ethnic groups, with 2.39% of YLL due to overdose, while only making up 0.80% of the population. During the last two years of the study, only American Indian/Native American and Black individuals had increased rates of mortality when compared to other races. During the ten-year study period, when including the top three causes of mortality, unintentional drug overdoses made up 11.98% of the YLL overall and 46.39% of accidents. For the years 2016-2019, YLL due to unintentional overdose was the third leading cause of YLL overall for this population., Conclusions: Unintentional drug overdose is a leading cause of death for perinatal individuals in the United States, claiming nearly 84,000 years of life over a ten-year period. When examining by race, American Indian/Native American women are most disproportionately affected., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: We performed RNA sequencing with the primary goal of discovering key placental villous trophoblast (VT) and decidua basalis (DB) transcripts differentially expressed in intra-amniotic infection (IAI)-induced preterm birth (PTB)., Methods: RNA was extracted from 15 paired VT and DB specimens delivered of women with: 1) spontaneous PTB in the setting of amniocentesis-proven IAI and histological chorioamnionitis (n = 5); 2) spontaneous idiopathic PTB (iPTB, n = 5); and 3) physiologic term pregnancy (n = 5). RNA sequencing was performed using the Illumina HiSeq 2500 platform, and a spectrum of computational tools was used for gene prioritization and pathway analyses., Results: In the VT specimens, 128 unique long transcripts and 7 mature microRNAs differed significantly between pregnancies complicated by IAI relative to iPTB (FDR<0.1). The up-regulated transcripts included many characteristic of myeloblast-derived cells, and bioinformatic analyses revealed enrichment for multiple pathways associated with acute inflammation. In an expanded cohort including additional IAI and iPTB specimens, the expression of three proteins (cathepsin S, lysozyme, and hexokinase 3) and two microRNAs (miR-133a and miR-223) was validated using immunohistochemistry and quantitative PCR, respectively. In the DB specimens, only 11 long transcripts and no microRNAs differed significantly between IAI cases and iPTB controls (FDR<0.1). Comparison of the VT and DB specimens in each clinical scenario revealed signatures distinguishing these placental regions., Discussion: IAI is associated with a transcriptional signature consistent with acute inflammation in the villous trophoblast. The present findings illuminate novel signaling pathways involved in IAI, and suggest putative therapeutic targets and potential biomarkers associated with this condition., (Copyright © 2016. Published by Elsevier Ltd.)

Arsenic trioxide, As2O3 (ATO), has been found to be an effective chemotherapeutic for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSaII tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5 to 42.5 degrees C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFalpha are noticeably increased in tumors 2 to 6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.

The interaction between recombinant Strongylocentrotus purpuratus sperm bindin and a recombinant fragment of the putative egg bindin receptor of the same species was measured in vitro. In solution these molecules interact with simple bimolecular kinetics, displaying an equilibrium dissociation constant of about 0.1 microM. Thus, as implied by many observations in vivo and in vitro, bindin and the putative egg receptor display a specific affinity for one another.

We have analyzed the binding of Sp1, a ubiquitously expressed transactivator, to the promoter region of the gamma genes. Low-affinity Sp1 sites were found at -50 and -200. A high-affinity site was detected at -140, over the CACCC sequence. To analyze the function of these sites, Drosophila SL-2 cells, which lack Sp1, were cotransfected with an Sp1 expression plasmid and gamma globin promoter-CAT constructs. In these assays, the gamma promoter was significantly stronger in the presence than in the absence of Sp1. Thus, the three Sp1 sites in the gamma promoter allow binding as well as transactivation of the promoter. The majority of this transactivation was due to the strong binding site at -140 because introduction of a point mutation at -144 (CACCC----AACCC) reduced Sp1-dependent promoter strength by 57%. Analysis of the -200 region suggested that in the wild-type promoter, Sp1 binding at this site contributes little to promoter strength. However, a point mutation (-198 T----C) associated with hereditary persistence of fetal hemoglobin (HPFH) dramatically increased the affinity of this site for Sp1 and significantly increased Sp1 dependent promoter strength in SL-2 cells. Three other point mutations associated with HPFH did not significantly affect the interaction of Sp1 with the -200 region.