Human Plasmacytoid Dendritic Cells Express C-Type Lectin Receptors and Attach and Respond to Aspergillus fumigatus.

Plasmacytoid dendritic cells (pDCs) have been implicated as having a role in antifungal immunity, but mechanisms of their interaction with fungi and the resulting cellular responses are not well understood. In this study, we identify the direct and indirect biological response of human pDCs to the fungal pathogen Aspergillus fumigatus and characterize the expression and regulation of antifungal receptors on the pDC surface. Results indicate pDCs do not phagocytose Aspergillus conidia, but instead bind hyphal surfaces and undergo activation and maturation via the upregulation of costimulatory and maturation markers. Measuring the expression of C-type lectin receptors dectin-1, dectin-2, dectin-3, and mannose receptor on human pDCs revealed intermediate expression of each receptor compared with monocytes. The specific dectin-1 agonist curdlan induced pDC activation and maturation in a cell-intrinsic and cell-extrinsic manner. The indirect activation of pDCs by curdlan was much stronger than direct stimulation and was mediated through cytokine production by other PBMCs. Overall, our data indicate pDCs express various C-type lectin receptors, recognize and respond to Aspergillus hyphal Ag, and serve as immune enhancers or modulators in the overarching fungal immune response.

Maternal antepartum antibiotic administration and patterns of bacterial resistance in early preterm neonates.

OBJECTIVE: The objective of this study was to determine the relationship between maternal antepartum antibiotic administration and antibiotic resistance patterns in preterm neonates admitted to the neonatal intensive care unit (NICU). METHODS: This was a retrospective cohort study of women and their preterm neonates delivered at a single tertiary care center over a 5-year period. Women and neonates were included if they delivered between 23 weeks 0 days and 28 weeks 6 days of gestation and neonates were admitted to the NICU. Subjects were excluded if there was incomplete antibiotic administration data or incomplete laboratory or bacterial culture data for either mothers or neonates. Data collected from maternal and neonatal charts included the type, duration, and total number of antibiotics administered to subjects, neonatal culture results within the first 7 days of life, and bacterial antibiotic resistance information. Women with neonates that cultured positive for bacteria demonstrating antibiotic resistance were compared to those whose neonates did not have antibiotic-resistant bacteria. RESULTS: 79 women with 90 neonates met inclusion criteria. Of the 79 women, 71 (89.9%) received at least 1 antibiotic antepartum. 14 neonatal bacterial isolates were resistant to at least 1 antibiotic. Antibiotic-resistant bacteria were present in 11 neonates; 3 neonates had more than 1 resistant bacteria cultured. The most common resistant bacteria cultured were Coagulase-negative Staphylococcus (6/14, 42.9%), S. aureus (3/14, 21.4%), and E. coli (2/14, 14.3%). Enterobacter spp (2) and Klebsiella pneumoniae (1) made up the remainder. Of the 11 neonates with resistant bacteria isolated, 10 of their mothers received antibiotics antepartum. Neonates with antibiotic-resistant bacterial isolates were more likely to be born at lower gestational ages (24.6 vs 25.9 weeks, p = .013) and have lower mean birth weights (679.5 vs 849.3 g, p = .009) than those without resistant bacteria. In 8 of 11 (73%) neonates with resistant bacteria, the mother received an antibiotic to which the bacteria cultured were resistant: 6 coagulase-negative Staphylococcus, 1 MRSA, and 1 S. aureus. CONCLUSIONS: Although preterm neonates are often treated for presumed sepsis, they infrequently have positive bacterial cultures. In this study, those that had positive bacterial cultures for resistant bacteria were born at earlier gestational ages and had lower birth weights. These bacteria cultured in neonates are likely to be resistant to antibiotics received by mothers in the antepartum period. Careful selection of maternal and neonatal antibiotics in the preterm setting with consideration for local antibiotic resistance patterns is suggested.

Senescence-associated ß-galactosidase reveals the abundance of senescent CD8+ T cells in aging humans.

Aging leads to a progressive functional decline of the immune system, rendering the elderly increasingly susceptible to disease and infection. The degree to which immune cell senescence contributes to this decline remains unclear, however, since markers that label immune cells with classical features of cellular senescence accurately and comprehensively have not been identified. Using a second-generation fluorogenic substrate for ß-galactosidase and multi-parameter flow cytometry, we demonstrate here that peripheral blood mononuclear cells (PBMCs) isolated from healthy humans increasingly display cells with high senescence-associated ß-galactosidase (SA-ßGal) activity with advancing donor age. The greatest age-associated increases were observed in CD8+ T-cell populations, in which the fraction of cells with high SA-ßGal activity reached average levels of 64% in donors in their 60s. CD8+ T cells with high SA-ßGal activity, but not those with low SA-ßGal activity, were found to exhibit features of telomere dysfunction-induced senescence and p16-mediated senescence, were impaired in their ability to proliferate, developed in various T-cell differentiation states, and had a gene expression signature consistent with the senescence state previously observed in human fibroblasts. Based on these results, we propose that senescent CD8+ T cells with classical features of cellular senescence accumulate to levels that are significantly higher than previously reported and additionally provide a simple yet robust method for the isolation and characterization of senescent CD8+ T cells with predictive potential for biological age.

Challenges and opportunities to understand, discuss, and decrease maternal mortality rates in the United States. The New Jersey experience.

Maternal mortality improvement depends on the proper classification used in defining maternal deaths. Since there are several definitions of maternal deaths depending upon the proximate cause of the death, if the death is related to the physiologic changes during pregnancy or not and the timing of the death, some opportunities for improvement may be missed to decrease the overall maternal mortality rate in the USA if the correct definition is not utilized appropriately.

Maternal morbidity after early preterm delivery (23-28 weeks).

BACKGROUND: Previous research has focused mainly on neonatal outcomes associated with preterm and periviable delivery, but maternal outcomes with preterm delivery are less well described. OBJECTIVE: This study aimed to determine if early preterm delivery results in an increase in maternal morbidity. STUDY DESIGN: This is a retrospective cohort study conducted at a tertiary care center over a 5-year time period. Subjects were women identified by review of neonatal intensive care unit admission logs. Women were included if they delivered between 23 0/7 and 28 6/7 weeks' gestation and their neonate was admitted to the neonatal intensive care unit. The prevalence of maternal morbidities was assessed, including blood transfusion, maternal infection, placental abruption, postpartum depression or positive depression screen, hemorrhage, and prolonged maternal postpartum hospitalization. A composite outcome comprising blood transfusion, maternal infectious morbidity, placental abruption, and postpartum depression was developed. Outcomes for women who delivered between 23 0/7 and 25 6/7 weeks' gestation (early group) and 26 0/7 and 28 6/7 weeks' gestation (late group) were compared. Multivariate logistic regression analysis was performed to evaluate contributors to the composite morbidity, controlling for confounding. RESULTS: A total of 82 women met the inclusion criteria: 38 in the early group and 44 in the late group. Maternal demographics were similar between the groups. The early group was significantly more likely to experience composite maternal morbidity (60.5% vs 27.3%; P=.004) and infection (42.1% vs 13.6%; P=.006). Regression analysis determined that delivery at a later gestational age was associated with lower rates of composite morbidity (odds ratio, 0.6; 95% confidence interval, 0.41-0.83). CONCLUSION: In this study, data suggest that maternal morbidity is higher with delivery at periviable gestational ages. Composite morbidity and maternal infection were more frequent in women who delivered at less than 26 weeks' gestation. The management of women at risk for delivery at early gestational ages should include a discussion of increased maternal complications.

Factors associated with attendance at the postpartum blood pressure visit in pregnancies complicated by hypertension.

OBJECTIVES: Women with hypertensive disorders of pregnancy should have a blood pressure evaluation no later than 7-10 days after delivery. The objective of this study was to identify the factors associated with patient attendance at the postpartum blood pressure follow-up visit. STUDY DESIGN: This was a retrospective cohort study of postpartum women who had a hypertensive disorder of pregnancy. Postpartum follow-up rates were recorded, and characteristics of women who attended a postpartum visit for blood pressure evaluation were compared to women who did not return for the visit. Multiple logistic regression was performed. MAIN OUTCOME MEASURES: Characteristics of women who returned for a blood pressure visit. RESULTS: There were 378 women who met inclusion criteria; 193(51.1%) attended the blood pressure visit. Women who returned were older and more likely to have preeclampsia, severe features, magnesium sulfate use, or severe hypertension during hospitalization. They were less likely to have gestational hypertension. Adjusted analysis demonstrated that black/non-Hispanic women (OR 0.53, 95% CI 0.34-0.83), the presence of any preeclampsia diagnosis (OR 2.19, 95% CI 1.03-4.81), and whether the woman underwent a cesarean delivery (OR 3.06, 95% CI 1.85-5.14) remained significant factors in predicting adherence. CONCLUSIONS: Women who returned for a blood pressure visit were more likely to have had significant hypertensive disease or a cesarean delivery. Non-Hispanic black women had the lowest rate of follow-up. Given black women have the highest rates of maternal morbidity and mortality nationwide, effective interventions to increase follow-up for them are needed.

Impact of Immigration and Duration of Residence in US on Length of Gestation Among Black Women in Newark, New Jersey.

Little is known about pregnancy outcomes of black immigrant women to the US. We surveyed 447 black women post-partum in two hospitals in Newark, NJ. Length of gestation was obtained from medical records. Covariates and information on immigration were collected by in-person interview. Risks ratios for preterm birth (< 37 weeks) comparing immigrant to US-born women were calculated using log-binomial regression. Associations with gestational age at delivery were estimated using linear regression. Multivariable models adjusted for socioeconomic and social/behavioral variables. Immigrant women relative to US-born women had a 60% lower risk of preterm birth (adjusted risk ratio = 0.4; 95% confidence interval (CI) 0.2, 0.8) and longer gestation (adjusted difference = 1.4 weeks, 95%CI 0.6, 2.1). Gestation was 1.9 weeks longer for recent immigrants compared to US-born women (95%CI 0.2, 3.6), whereas for those who lived in the US for at least 10 years there was no difference. The healthy immigrant effect found among black immigrants may erode with time in the US.

Evaluation of a Multilevel Intervention to Reduce Preterm Birth Among Black Women in Newark, New Jersey: A Controlled Interrupted Time Series Analysis.

Objective To evaluate the effectiveness of a multilevel intervention, Healthy Babies are Worth the Wait (HBWW), in reducing preterm birth (PTB) and very preterm birth (VPTB) among black women in Newark, NJ. Methods HBWW is a program linking the local March of Dimes office, providers, community-based organizations, and public health institutions to increase uptake of evidence based preterm birth interventions. We used birth certificate data before (2009-2011) and after (2012-2015) the introduction of HBWW in Newark. We estimated differences in PTB and VPTB between these periods among black women in Newark and compared them to rate differences among black women in the rest of NJ (difference-in-differences). We used interrupted time series analysis (ITSA) to examine declines in PTB and VPTB following the introduction of HBWW controlling for secular trends. All models adjusted for maternal age, education and parity. Results PTB declined in Newark 1.1 case per 100 (95% confidence interval (CI) - 2.3, 0) and in the rest of NJ 0.5 case per 100 (- 1.4, 0.4) (difference-in-differences = 0.6 fewer cases per 100 in Newark, 95% CI - 1.6, 0.3). VPTB declined in both Newark (- 0.6 cases per 100, 95% CI - 1.0, 0) and the rest of NJ (- 0.2 cases per 100, 95% CI - 0, 0.3) (difference-in-differences = 0.4 fewer cases per 100 in Newark, 95% CI - 0.9, 0). However, using ITSA the downward VPTB trend in Newark was not different from the rest of NJ or pre-intervention trends. Conclusions for Practice Our study supports the importance of critically evaluating and advancing complex interventions to reduce PTB among black women.

Genital tract GBS and rate of histologic chorioamnionitis in patients with preterm premature rupture of membrane.

INTRODUCTION: Histologic chorioamnionitis (HC) is a common finding in the placenta from patients with preterm premature rupture of membranes (PPROM). The purpose of this study is to determine if HC differs based on the Group B streptococcus (GBS) status in patients managed expectantly with PPROM <34 weeks gestation. METHODS: A retrospective study was performed of patients admitted with PPROM between 23 0/7 and 33 6/7 weeks from 2003 to 2014 at one institution. Patients were excluded if in labor, evidence of clinical chorioamnionitis, nonreassuring fetal status, multifetal gestation, HIV positive, or if GBS specimens or placental histology were not available. Placental pathology results were compared using Fisher's exact test. RESULTS: One hundred eighty-one patients met inclusion criteria and 55 (30.3%) were GBS positive. The prevalence of HC did not differ between the GBS positive and GBS negative groups (69 versus 64.2%, respectively; p = .62). Clinical chorioamnionitis, endomyometritis, wound infection, maternal and neonatal sepsis did not differ between the two groups. CONCLUSIONS: Vaginal-rectal colonization with GBS on admission does not appear to affect the rate of HC nor neonatal outcome in patients managed conservatively with PPROM <34 weeks gestation.

Salmonella enterica Serotype Typhi Bacteremia Complicating Pregnancy in the Third Trimester.

Background. Salmonella enterica serotype Typhi (S. Typhi) is an anaerobic gram-negative enteric rod that causes infection when contaminated food or water is ingested and may cause illness in pregnancy. Case. This is a patient who presented at 31 weeks' gestation with abdominal pain and fever and was diagnosed with S. Typhi bacteremia. Conclusion. S. Typhi should be considered in febrile patients with recent travel presenting with abdominal discomfort with or without elevated liver enzymes.

Contemporary management of shoulder dystocia.

Shoulder dystocia is an uncommon but potentially catastrophic intrapartum event. Although risk factors such as maternal diabetes, obesity and macrosomia can be identified, shoulder dystocia most frequently occurs in patients who lack risk factors. Many maneuvers have been described to assist the operator in the safe release of the shoulder and subsequent delivery; however, no prospective trials have compared these maneuvers in such a way to suggest that one maneuver is superior to another. This article describes the identification of patients at risk for shoulder dystocia, clinical management of the shoulder dystocia, event documentation and the contemporary use of drills and simulation training to improve team preparedness for this unpredictable and usually unavoidable event.

Risk factors for hepatitis C infection among sexually transmitted disease-infected, inner city obstetric patients.

OBJECTIVE: To test the hypothesis that our inner city obstetric patients who have been infected with sexually transmitted diseases (STDs) will have a higher prevalence of hepatitis C virus infection than the general population and to identify specific risk factors and high-risk groups. METHODS: All patients in our prenatal clinic (July 1997-April 1999) who tested positive for one or more STDs were asked to return for hepatitis C antibody testing. Medical charts of all patients who returned for hepatitis C testing were reviewed. RESULTS: A total of 106 patients with STDs were tested for hepatitis C. Positive screening tests for anti-hepatitis C antibody were found in 6.6% (7/106) of the patients (95% CI = 2.7-13.1%). This frequency is significantly higher than the hepatitis C prevalence (1.8%) in the general United States population (p = 0.006). Multiple logistic regression analysis confirmed only older age (p = 0.0 16) and positive HIV status (p = 0.023) to be significant predictors of hepatitis C infection. CONCLUSIONS: Inner city STD-infected obstetric patients are at high risk for hepatitis C infection compared with the general population. Increasing age and HIV-positive status are risk factors which are significantly associated with hepatitis C infection.

Vitamin profile of 563 gravidas during trimesters of pregnancy.

OBJECTIVE: Gestation imposes metabolic stress on the mother which heightens as pregnancy progresses. The need for quantifying circulating vitamins is important for identifying pitfalls in metabolic imbalance and nutritional status. For this reason we wanted to analyze blood vitamin concentrations of B12, thiamin, biotin, pantothenate, B6, niacin, riboflavin, folate, vitamins A, C, E and total carotenes to determine if imbalances occur during the trimesters of pregnancy. METHODS: We randomly selected 563 gravidas who volunteered for this study from the obstetrical clinic of New Jersey Medical School; 132 were in 1st trimester, 198 were in 2nd trimester, and 233 were in 3rd trimester. All were healthy, taking a good diet and supplemented with vitamins. Blood, from an antecubital vein, was analyzed for thiamin, biotin, B12, B6, pantothenate, riboflavin, nicotinate, folates, vitamins A, E, C and total carotenes. Gravidas were classified as being normovitaminemic, hypervitaminemic or hypovitaminemic compared with blood vitamins seen in healthy non-pregnant, non-vitamin supplemented women. RESULT: Hypervitaminemic levels of folate, biotin, pantothenate and riboflavin were found during any trimester of pregnancy due to vitamin supplementation. Despite the vitamin supplementation, a high percent of vitamin A, B6, niacin. thiamin and B 12 hypovitaminemia was noted during pregnancy trimesters. An especially high percentage of niacin deficiency was seen during the 1st trimester; it worsened in later trimesters; B12 deficits increased during the late trimesters. Combination deficits of niacin, thiamin, vitamins A, B6, B12 were noted in each of the trimesters. CONCLUSIONS: Despite vitamin supplementation, a vitamin profile of pregnancy indicates that vitamin deficits exist during the trimesters. Also, combination hypovitaminemias of deficient vitamins were noted; this indicates that a vitamin deficit during pregnancy does not occur in isolation.