Retrospective Analysis of the Serologic Response to the Treatment of Syphilis During Pregnancy

Objective: The purpose of this study was to assess the effect of several maternal variables on the serologic response following the treatment of syphilis in pregnancy

Intravenous Penicillin for Antenatal Syphilotherapy

A 21 year old woman (G2 P0101) of 24 weeks gestation presented with syphilis of unknown duration. Sonography revealed fetal hydrops and placental thickening. Weekly intramuscular injections of 2.4 million U Bicillin for 3 weeks was initiated as recommended by the Centers for Disease Control. Repeat sonogram 1 week after starting treatment revealed increased ascites and a new pericardial effusion. Due to the worsening fetal condition, therapy was altered and the patient was admitted for IV penicillin. She received a continuous infusion of 18 million U penicillin G daily for 10 days. Serial sonograms showed improvement offetal ascites and pericardial effusion with 10 days of IV therapy, and complete resolution of hydrops was noted within 3 weeks. The fetus was born at term with no stigmata of congenital syphilis on newborn exam, and laboratory tests suggested adequate treatment in utero

Umbilical uptakes and transplacental concentration ratios of amino acids in severe fetal growth restriction

Background: This study examines the relationship between placental amino acid (AA) transport and fetal AA demand in an ovine fetal growth restriction (FGR) model in which placental underdevelopment induces fetal hypoxemia and hypoglycemia. Methods: Umbilical uptakes of AA, oxygen, glucose, and lactate were measured near term in eight experimental ewes (FGR group) and in eight controls (C group). Results: The FGR group demonstrated significantly reduced umbilical uptakes of oxygen, glucose, lactate, and 11 AAs per kg fetus. The combined uptake of glucose, lactate, and AAs, expressed as nutrient/oxygen quotients, was reduced almost to 1.00 (FGR: 1.05 vs. C: 1.32, P ≤ 0.02). In contrast to a decrease in umbilical glucose concentration, all but one of the AAs that were transported from placenta to fetus demonstrated normal or elevated fetal concentrations, and five of the essential AAs were transported against a significantly higher feto/maternal (F/M) concentration ratio. This ratio peaked at the lowest fetal oxygen levels. Conclusion: We conclude that, in the hypoxic FGR fetus, the reduction in AA uptake is not due to a disproportionally small placental AA transport capacity. It is the consequence of decreased fetal oxidative metabolism and growth rate, which together reduce fetal AA demand. © 2013 International Pediatric Research Foundation, Inc

Analysis of Interactions of Salmonella Type Three Secretion Mutants with 3-D Intestinal Epithelial Cells

The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS) is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2), double (SPI-1/2) and complete T3SS knockout (SPI-1/SPI-2: flhDC) also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms

SN 2022oqm: A Multi-peaked Calcium-rich Transient from a White Dwarf Binary Progenitor System

We present the photometric and spectroscopic evolution of SN 2022oqm, a nearby multi-peaked hydrogen- and helium-weak calcium-rich transient (CaRT). SN 2022oqm was detected 19.9 kpc from its host galaxy, the face-on spiral galaxy NGC 5875. Extensive spectroscopic coverage reveals a hot (T >= 40,000 K) continuum and carbon features observed ~1 day after discovery, SN Ic-like photospheric-phase spectra, and strong forbidden calcium emission starting 38 days after discovery. SN 2022oqm has a relatively high peak luminosity (MB = -17 mag) for CaRTs, making it an outlier in the population. We determine that three power sources are necessary to explain SN 2022oqm's light curve, with each power source corresponding to a distinct peak in its light curve. The first peak of the light curve is powered by an expanding blackbody with a power law luminosity, consistent with shock cooling by circumstellar material. Subsequent peaks are powered by a double radioactive decay model, consistent with two separate sources of photons diffusing through an optically thick ejecta. From the optical light curve, we derive an ejecta mass and 56Ni mass of ~0.89 solar masses and ~0.09 solar masses, respectively. Detailed spectroscopic modeling reveals ejecta that is dominated by intermediate-mass elements, with signs that Fe-peak elements have been well-mixed. We discuss several physical origins for SN 2022oqm and favor a white dwarf progenitor model. The inferred ejecta mass points to a surprisingly massive white dwarf, challenging models of CaRT progenitors.Comment: 33 pages, 17 figures, 5 tables, Submitted to Ap

The Pore-Forming Toxin Listeriolysin O Mediates a Novel Entry Pathway of L. monocytogenes into Human Hepatocytes

Intracellular pathogens have evolved diverse strategies to invade and survive within host cells. Among the most studied facultative intracellular pathogens, Listeria monocytogenes is known to express two invasins-InlA and InlB-that induce bacterial internalization into nonphagocytic cells. The pore-forming toxin listeriolysin O (LLO) facilitates bacterial escape from the internalization vesicle into the cytoplasm, where bacteria divide and undergo cell-to-cell spreading via actin-based motility. In the present study we demonstrate that in addition to InlA and InlB, LLO is required for efficient internalization of L. monocytogenes into human hepatocytes (HepG2). Surprisingly, LLO is an invasion factor sufficient to induce the internalization of noninvasive Listeria innocua or polystyrene beads into host cells in a dose-dependent fashion and at the concentrations produced by L. monocytogenes. To elucidate the mechanisms underlying LLO-induced bacterial entry, we constructed novel LLO derivatives locked at different stages of the toxin assembly on host membranes. We found that LLO-induced bacterial or bead entry only occurs upon LLO pore formation. Scanning electron and fluorescence microscopy studies show that LLO-coated beads stimulate the formation of membrane extensions that ingest the beads into an early endosomal compartment. This LLO-induced internalization pathway is dynamin-and F-actin-dependent, and clathrin-independent. Interestingly, further linking pore formation to bacteria/bead uptake, LLO induces F-actin polymerization in a tyrosine kinase-and pore-dependent fashion. In conclusion, we demonstrate for the first time that a bacterial pathogen perforates the host cell plasma membrane as a strategy to activate the endocytic machinery and gain entry into the host cell

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexit

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP