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Summary: Background: The human microbiome project addresses the relationship between bacterial flora and the human host, in both healthy and diseased conditions. The skin is an ecosystem with multiple niches, each featuring unique physiological conditions and thus hosting different bacterial populations. The skin microbiome has been implicated in the pathogenesis of many dermatoses. Given the role of dysbiosis in the pathogenesis of inflammation, which is prominent in dystrophic epidermolysis bullosa (DEB), we undertook a study on the skin microbiome. Aim: To characterize the skin microbiome in a series of patients with DEB. Methods: This was a case–control study of eight patients with DEB and nine control cases enrolled between June 2017 and November 2018. The skin of patients with DEB was sampled at three different sites: untreated wound, perilesional skin and normal‐appearing (uninvolved) skin. Normal skin on the forearm was sampled from age‐matched healthy controls (HCs). We used a dedicated DNA extraction protocol to isolate microbial DNA, which was then analysed using next‐generation microbial 16S rRNA sequencing. Data were analysed using a series of advanced bioinformatics tools. Results: The wounds, perilesional and uninvolved skin of patients with DEB demonstrated reduced bacterial diversity compared with HCs, with the flora in DEB wounds being the least diverse. We found an increased prevalence of staphylococci species in the lesional and perilesional skin of patients with DEB, compared with their uninvolved, intact skin. Similarly, the uninvolved skin of patients with DEB displayed increased staphylococcal content and significantly different microbiome diversities (other than staphylococci) compared with HC skin. Conclusions: These findings suggest the existence of a unique DEB‐associated skin microbiome signature, which could be targeted by specific pathogen‐directed therapies. Moreover, altering the skin microbiome with increasing colonization of bacteria associated with nonchronic wounds may potentially facilitate wound healing in patients with DEB. [ABSTRACT FROM AUTHOR]

Summary: Background: The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture. Objectives: To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment. Methods: Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI‐TOF) in a prospective study. Results: Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in lesional sites were reflected in similar changes in culturable bacteria, although changes in the microbiota over repeated swabbing were detectable only with sequencing. The composition of the microbial communities varied by skin site and microenvironment. Prevotella and Staphylococcus were significantly associated with lesional skin, and Anaerococcus and Propionibacterium with nonlesional skin. There were no significant differences in the amount of bacteria cultured from the skin of healthy controls and patients with psoriasis. Conclusions: Shifts in the cutaneous microbiome in psoriasis, particularly during treatment, may shed new light on the pathogenesis of the disease and may be clinically exploited to predict treatment response. What's already known about this topic? Alterations in the composition of the cutaneous microbiome have been described in psoriasis, although methodological differences in study design prevent direct comparison of results.To date, most cutaneous microbiome studies have focused on 16S rRNA sequencing data, including both living and dead bacteria. What does this study add? This prospective observational study confirms that changes in the composition of the cutaneous microbiome, detected by 16S rRNA sequencing, are consistent with those identified by bacterial culture and mass spectrometry.The changes in the microbiome during antipsoriasis therapy should be further investigated to determine whether these represent potential novel biomarkers of treatment response. What is the translational message? Characterization of cutaneous microbiota may ultimately move into the clinic to help facilitate treatment selection, not only by optimizing currently available treatments, but also by identifying new therapeutic targets. Respond to this article Linked Comment: Tobin. Br J Dermatol 2019; 181:1124–1125. [ABSTRACT FROM AUTHOR]

Objective This study aims to evaluate the association between prepregnancy body mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes mellitus (DM). Methods This is a secondary analysis of a cohort of 426 pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women were categorized according to prepregnancy BMI: low BMI (< 20 kg/m²), normal BMI (20 to < 25 kg/m²), and high BMI (≥ 25 kg/m²). The outcomes of interest were: spontaneous abortion (delivery < 20 weeks gestation); preeclampsia; emergent delivery for maternal indications (hypertension or placental abruption); and preterm delivery (< 37 weeks gestation). Analyses included proportional hazards and multiple logistic regression models with covariates: age, age at diagnosis of type 1 DM, previous spontaneous abortion, microvascular disease (nephropathy or retinopathy), and glycohemoglobin A1 concentrations. Results Low BMI was associated with preterm delivery. High BMI was associated with emergent delivery for maternal indications. Glycemic control as measured by glycohemoglobin A1 was associated with increased risk of spontaneous abortion, attenuating the association with low prepregnancy weight. Conclusion Prepregnancy BMI is a risk factor to be considered when caring for women with type 1 DM, in particular for preterm delivery (low BMI) and emergent delivery for maternal indications (high BMI). [ABSTRACT FROM AUTHOR]

Objective The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. Study Design This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. Results CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. Conclusion Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the association between body mass index (BMI) and the delivery of an asymmetrically large for gestational age (A-LGA) newborn in women with diabetes.Methods: Retrospective analysis of 306 pregnancies complicated by Type 1 and 55 by Type 2 diabetes.Results: The prevalence of Type 1 and Type 2 diabetics delivering large for gestational age (LGA) infants was 42% and 49%, respectively. Of these 49% and 55% were A-LGA, respectively. Pre-pregnancy BMI was not associated with increased odds of delivering an A-LGA newborn in women with Type 1 or 2 diabetes. However, in Type 1 diabetics, each one-pound increase in maternal weight during pregnancy resulted in 4% increased odds of delivering an A-LGA newborn. For Type 2 diabetics, the odds of delivering an A-LGA infant was decreased by 10% for each 0.1 unit/kg increase in insulin dose.Conclusion: Although there is a known association between obesity and LGA in women with diabetes, we found that overweight and obese women with Type 1 or Type 2 diabetes do not have increased odds of delivering an A-LGA newborn. However, insulin dose in Type 2 diabetes and maternal weight gain in Type 1 diabetes were significantly associated with the odds of delivering an A-LGA neonate. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that fetal exposure to a hyperglycemic intrauterine environment in women with type 1 diabetes is associated with asymmetrically distributed excessive fetal growth and imprinting consistent with adverse health issues later in life.Methods: We report findings from a feasibility study on 19 young adults, born to mothers with type 1 diabetes. Long-term follow-up of the offspring in young adulthood included: oral glucose tolerance test, body mass index (BMI), dual X-ray absorptiometry, and blood pressure (BP). We report z-BMI and z-BP to account for varying gender and age.Results: The young adults born to women with diabetes averaged 19.9 years at follow-up; 37% were female, and 21% African American. Maternal glycohemoglobin A(1) concentration in the 2nd trimester was 9.2% for offspring born with asymmetric LGA and 7.5% for those born with symmetric LGA or AGA. There was significant correlation between maternal glucose control during pregnancy and fasting glucose, z-BMI and z-systolic BP in the young adults.Conclusion: The hyperglycemic intrauterine environment is associated with short-term morbidity, manifested as asymmetric LGA (the "fat" baby). In addition, increasing level of maternal hyperglycemia during pregnancy is associated with increased adiposity and elevated fasting glucose in the young adult offspring. [ABSTRACT FROM AUTHOR]

Glyburide's pharmacokinetics (PK) and pharmacodynamics have not been studied in women with gestational diabetes mellitus (GDM). The objective of this study was to assess steady-state PK of glyburide, as well as insulin sensitivity, β-cell responsivity, and overall disposition indices after a mixed-meal tolerance test (MMTT) in women with GDM (n = 40), nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 26), and healthy pregnant women (n = 40, MMTT only). At equivalent doses, glyburide plasma concentrations were ~50% lower in pregnant women than in nonpregnant subjects. The average umbilical cord/maternal plasma glyburide concentration ratio at the time of delivery was 0.7 ± 0.4. Insulin sensitivity was approximately fivefold lower in women with GDM as compared with healthy pregnant women. Despite comparable β-cell responsivity indices, the average β-cell function corrected for insulin resistance was more than 3.5-fold lower in women with glyburide-treated GDM than in healthy pregnant women. Women with GDM in whom glyburide treatment has failed may benefit from alternative medication or dosage escalation; however, fetal safety should be kept in mind.Clinical Pharmacology & Therapeutics (2009); 85, 6, 607–614 doi:10.1038/clpt.2009.5 [ABSTRACT FROM AUTHOR]

Studies the consequences of smoking and caffeine consumption during pregnancy in women with type 1 diabetes. Risks of adverse maternal and perinatal outcomes; Glycemic control; Risks of spontaneous abortion; Occurrence of pre-eclempsia.

ABSTRACT Objective To test the null hypothesis that no correlation exists between transvaginal digital examination compared with the gold standard technique of transabdominal suprapubic ultrasound assessment of fetal head position during the second stage of labor. A secondary objective was to compare the performance of attending physicians vs. senior residents in depicting fetal head position by transvaginal digital examination in comparison with ultrasound assessment. Methods Consecutive patients in the second-stage of labor at term with normal singleton cephalic-presenting fetuses and ruptured membranes were included. Transvaginal digital examinations were performed by either attending physicians or senior residents and were followed immediately by transverse suprapubic transabdominal sonographic assessments performed by a single sonographer. Examiners were blinded to each other’s findings. Power analysis dictated sample size. Exact binomial confidence intervals around observed rates were compared with χ2 and Cohen’s κ-tests. Logistic regression was applied. P < 0.05 was considered significant throughout. Results One hundred and twelve patients were studied. The absolute error of transvaginal digital examinations was recorded in 65% of patients (95% confidence interval, 56–74%). Parity, pelvic station, combined spinal epidural anesthesia, length of first or second stages of labor, use of oxytocin augmentation, gestational age, mode of delivery, birth weight, and examiner experience did not significantly affect examination accuracy. Stratification, when the transvaginal digital examination was recorded as correct if occurring within ± 45° of the ultrasound assessment, reduced the error of the transvaginal digital examinations to 39% (95% confidence interval, 30–49%). Independent variables again did not affect examination accuracy in this assessment modality. Rates of agreement between the two methods... [ABSTRACT FROM AUTHOR]

To determine the factors associated with an increased risk of developing varicella-zoster virus (VZV) pneumonia during pregnancy, a case-control analysis was done in which 18 pregnant women with VZV pneumonia were compared with 72 matched control subjects. VZV infection was identified clinically, and VZV pneumonia was diagnosed by dyspnea and findings on chest radiographs. Of 347 pregnant women with VZV infection, 18 (5.2%) had pneumonia treated with acyclovir, and none died. Mean gestational age at rash onset was 25.8 plus minus 8.8 weeks for patients with pneumonia and 17.7 +/- 10.3 weeks for control subjects, which was not significant in the multivariable model. Women with VZV pneumonia were significantly more likely to be current smokers (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.6-16.7) and to have > or = 100 skin lesions (OR, 15.9; 95% CI, 1.9-130.2). Pregnant women with VZV infection may be more likely to develop varicella pneumonia if they are smokers or manifest > or = 100 skin lesions. © 2002 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]