Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk.

Early life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort ( = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals.

Progression of C-reactive protein from birth through preadolescence varies by mode of delivery.

Introduction: Delivery via caesarean section (C-section) has been associated with an increased risk of childhood chronic diseases such as obesity and asthma, which may be due to underlying systemic inflammation. However, the impact of specific C-section types may be differential, as emergency C-sections typically involve partial labor and/or membrane rupture. Our objectives were to determine if mode of delivery associates with longitudinal profiles of high sensitivity CRP (hs-CRP) -a marker of systemic inflammation-from birth through preadolescence, and to examine if CRP mediates the association between mode of delivery and preadolescent body mass index (BMI).

Inflammatory endotype of odontogenic sinusitis.

Background: Odontogenic sinusitis (ODS) is distinct from non-odontogenic rhinosinusitis with regard to clinical features as well as diagnostic and therapeutic approaches. While numerous studies have explored immune profiles of chronic rhinosinusitis, very few studies have explored the inflammatory endotype of ODS.

Methods: Odontogenic sinusitis was diagnosed by confirming infectious sinusitis adjacent to infectious maxillary odontogenic pathology.

Association between cesarean delivery types and obesity in preadolescence.

Background/objectives: The association between mode of delivery and childhood obesity remains inconclusive. Because few studies have separated C-section types (planned or unplanned C-section), our objective was to assess how these subtypes relate to preadolescent obesity.

Subjects/methods: The study consisted of 570 maternal-child pairs drawn from the WHEALS birth cohort based in Detroit, Michigan.

Validating an algorithm for multiple myeloma based on administrative data using a SEER tumor registry and medical record review.

Purpose: Large numbers of multiple myeloma patients can be studied in real-world clinical settings using administrative databases. The validity of these studies is contingent upon accurate case identification. Our objective was to develop and evaluate algorithms to use with administrative data to identify multiple myeloma cases.

Breast Milk Transforming Growth Factor β Is Associated With Neonatal Gut Microbial Composition.

Background And Objectives: Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota.

Race-specific Association of Caesarean-Section Delivery with Body Size at Age 2 Years.

Objective: African American children are at higher risk of obesity than White children and African American women are more likely to undergo caesarean-section (CS) delivery than White women. CS is associated with childhood obesity; however, little is known whether this relationship varies by race. We examined if the association of CS with obesity at age 2 years varied by race.

Incidence of liver injury among cancer patients receiving chemotherapy in an integrated health system.

Purpose: Using liver laboratory tests (LLTs), Hy's law is a method used to identify drug-induced liver injury (DILI), after excluding other causes. Elevated LLTs in chemotherapy-exposed patients may result from tumor effects or comorbidities. This study evaluated incidence of Hy's law in chemotherapy-treated cancer patients.

Early pregnancy vitamin D and patterns of antenatal inflammation in African-American women.

Vitamin D is essential for the health of both mother and fetus during pregnancy. In the nonpregnant state, vitamin D demonstrates anti-inflammatory effects, but little is known about this relationship during pregnancy. African-American women are at a higher risk of vitamin D deficiency and for altered inflammatory responses during pregnancy.

Does pet-keeping modify the association of delivery mode with offspring body size?

Caesarean-section (CS) delivery increases risk of childhood obesity, and is associated with a distinct early-life gut microbiome, which may contribute to obesity. Household pets may alter human gut microbiome composition. We examined if pet-keeping modified the association of CS with obesity at age 2 years in 639 Wayne County Health, Environment, Allergy and Asthma Longitudinal Study birth cohort participants.

Differentiating asthma phenotypes in young adults through polyclonal cytokine profiles.

Background: Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiologic and clinical studies. Although allergic asthma and nonallergic asthma are frequently combined into 1 disease category in observational research and clinical trials, few studies have investigated the extent to which these 2 separate phenotypes are associated with distinct cytokine immunologic profiles in a representative young adult population.

Objective: To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and nonallergic asthma in a population-based birth cohort evaluated as young adults.

Cytokine patterns differ seasonally between women with and without uterine leiomyomata.

Problem: Uterine leiomyomata are the most common reproductive tumor in women, and their cause is not known.

Methods Of Study: Plasma samples from 155 women (74 with and 81 without ultrasound-confirmed leiomyoma) from a new study of leiomyoma risk factors in the Detroit, Michigan area, were examined for any cross-sectional associations between commonly examined cytokines and leiomyoma presence.

Results: Associations varied by season of sample collection defined a priori as winter (December-February) and non-winter seasons.

Regulatory T cells vary over bleeding segments in asthmatic and non-asthmatic women.

Sex hormones may play an important role in observed gender differences in asthma incidence and severity. Regulatory T cells (Treg cells) are presumed to be involved in asthma and may vary with hormone levels. To investigate the effects of sex hormones on levels of Treg cells (percentage of CD4+CD25+Foxp3+ lymphocytes that are CD127-), a cohort of 13 women (6 with and 7 without an asthma diagnosis) had blood drawn multiple times over the course of a bleeding segment (bleeding interval plus the following bleeding-free interval) and collected urine samples daily for measurement of estrogen (estrone E1C) and progesterone (pregnanediol-glucuronide PDG) metabolites.

PPARalpha expression protects male mice from high fat-induced nonalcoholic fatty liver.

Emerging evidence suggests that the lack of PPARα enhances hepatic steatosis and inflammation in Ppara-null mice when fed a high-fat diet (HFD). Thus, the aim of this study was to determine whether Ppara-null mice are more susceptible to nonalcoholic steatohepatitis (NASH) than their wild-type (WT) counterparts following short-term feeding with a HFD. Age-matched male WT and Ppara-null mice were randomly assigned to consume ad libitum a standard Lieber-DeCarli liquid diet (STD) (35% energy from fat) or a HFD (71% energy from fat) for 3 wk.

Within-woman change in regulatory T cells from pregnancy to the postpartum period.

Regulatory T cells (Treg cells) are an important area of investigation in human health and disease. In this study, the trajectory of percentage of Treg cells (defined as CD4+CD25+Foxp3+CD127--lymphocytes) was measured in the blood of 208 women during pregnancy and up to three additional times in the postpartum period (1, 6 and 12 months postpartum). Whether the trajectory was affected by gravidity, parity, neonatal sex, pet exposure, maternal atopic and asthma status, smoking, maternal race or other pregnancy factors was examined.

Man's best friend? The effect of pet ownership on house dust microbial communities.

Pet-ownership, which has been shown to be protective against allergic disease development, is associated with increased house dust bacterial diversity and fewer fungal species, suggesting a potentially microbial-based mechanism for this protective effect.

Variation of dust endotoxin concentrations by location and time within homes of young children.

Endotoxin may affect the development of allergic disease in childhood but little is known about endotoxin variation within homes. We sought to determine endotoxin concentration agreement within homes when five locations were each sampled twice 5 months apart. Endotoxin was measured using the recombinant Limulus factor C assay in dust samples from 585 homes of children enrolled in a prospective study and again in 335 homes 5 months later.

Regulatory T cells in prenatal blood samples: variability with pet exposure and sensitization.

Fetal exposures have come under investigation as risk factors of early life allergic disease. In this study we aimed to examine the relationships between dog or cat exposure and naturally occurring regulatory T cells (Treg cells), thought to play an important role in immune tolerance, in pregnant women. A cross-sectional analysis was conducted among 204 pregnant women who were queried regarding dog and cat exposure.

Polymorphisms in metabolic genes CYP1A1 and GSTM1 and changes in maternal smoking during pregnancy.

Introduction: Studies have documented the role of variations in genes that encode metabolic enzymes in altering the effects of maternal smoking on child health. We assessed the association of the MspI polymorphism in CYP1A1(*2A) and the null GSTM1 with maternal smoking behavior during pregnancy.

Methods: Smoking data for women during pregnancy were derived through in-person interviews and from genotyping data from buccal cell DNA for 165 smoking mothers (85% Black) accompanying their children to Children's Hospital of Michigan in Detroit.

Role of mechanical and redox stress in activation of mitogen-activated protein kinases in primary cultured rat hepatocytes.

Mechanical stress is known to activate signaling cascades, including mitogen-activated protein kinase (MAPK) pathways. Although mechanical stress has been implicated in hepatic cirrhosis and liver regeneration following hepatectomy, the signaling pathway(s) that may be activated in hepatocytes in response to mechanical stress have not been determined. Using primary cultured rat hepatocytes to examine cellular signaling in response to mechanical stress associated with medium change, we observed that the phosphorylation status of extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal kinase and p38 MAPK, but not Akt, was altered.

Acetoacetate induces CYP2E1 protein and suppresses CYP2E1 mRNA in primary cultured rat hepatocytes.

The ketone body acetoacetate (AA) in the absence of insulin or in the presence of diabetic insulin levels decreases CYP2E1 mRNA expression in a concentration- and time-dependent manner in primary cultured rat hepatocytes. AA activates p70 ribosomal S6 kinase (p70S6K) and protein kinase C (PKC) by approximately 2- to 2.5-fold, respectively, following 6-h treatment.

Insulin signaling regulates gamma-glutamylcysteine ligase catalytic subunit expression in primary cultured rat hepatocytes.

Decreased glutathione (GSH) levels and gamma-glutamylcysteine ligase (GCL) activity have been observed in diabetic patients, and insulin reportedly increases GSH synthesis via increased GCL catalytic subunit (GCLC) gene expression. The signaling pathways responsible for mediating insulin effects on GCLC expression and GSH levels, however, are unknown. The signaling pathways involved in the regulation of GSH synthesis in response to insulin were examined in primary cultured rat hepatocytes.

Acetoacetate activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase in primary cultured rat hepatocytes: role of oxidative stress.

Diabetes is characterized by elevated levels of ketone bodies acetoacetate (AA) and 3-hydroxybutyrate (3HB). High levels of ketone bodies have been implicated in generation of cellular oxidative stress. Ketone body activation of cellular signaling pathways associated with oxidative stress, however, has not been established.

Insulin and glucagon signaling in regulation of microsomal epoxide hydrolase expression in primary cultured rat hepatocytes.

Microsomal epoxide hydrolase (mEH) plays an important role in the detoxification of a broad range of epoxide intermediates and has been reported to be decreased during diabetes and fasting. The signaling pathways involved in the regulation of mEH expression in response to insulin and glucagon were examined in primary cultured rat hepatocytes. mEH protein levels were increased 2- to 6-fold in hepatocytes cultured for 1 to 4 days, respectively, in the presence of insulin.