Cost-Effectiveness of a Shock Team Approach in Refractory Cardiogenic Shock.

BACKGROUND: Multidisciplinary Shock Teams have improved clinical outcomes for cardiogenic shock, but their implementation costs have not been studied. This study's objective was to compare costs between patients treated with and without a Shock Team and determine if the team's implementation is cost-effective compared with standard of care. METHODS: We examined patients with refractory cardiogenic shock treated with or without a Shock Team at a tertiary academic hospital from 2009 to 2018. Real-world hospital data were used to compare costs and outcomes, including survival at discharge, 1-year survival, and quality-adjusted life years gained at 1 year. Incremental cost-effectiveness ratios were calculated over a 1-year time horizon, with parameter uncertainty evaluated through probabilistic sensitivity analysis using 1000 second-order Monte Carlo simulations. RESULTS: The study involved 244 patients, with 123 treated by the Shock Team and 121 receiving standard of care. Patients were predominantly male (77.5%), with a mean age of 58 (18-92) years. The Shock Team approach improved survival rates at hospital discharge and 1-year follow-up (61.0% versus 47.9%; P=0.04 and 55.0% versus 40.5%; P=0.03, respectively). The incremental cost-effectiveness ratio for increases in survival probability at discharge for the multidisciplinary Shock Team compared with standard of care was $102 088. The incremental cost-effectiveness ratio for increases in survival probability at 1-year was estimated at $96 152 and at $127 862 per 1 quality-adjusted life year gained. Probabilistic sensitivity analysis estimates showed that the Shock Team was cost-effective in the majority of simulations using a willingness-to-pay threshold of $150 000, while it was also dominant in almost one-third of the simulations. CONCLUSIONS: The Shock Team approach for treating refractory cardiogenic shock may be a cost-effective alternative to traditional standard of care. These findings can help prioritize the implementation of Shock Team initiatives to further improve cardiogenic shock outcomes.

Costs of medical evacuation and transportation of First Nations Peoples and Inuit who travel for medical care in Canada: A systematic review.

OBJECTIVE: For First Nations people and Inuit who live on reserves or in rural and remote areas, a guideline requires their travel to urban centres once their pregnancy reaches 36-38 weeks gestation age to await labour and birth. While not encoded in Canadian legislation, this guideline-and invisible policy-is reinforced by the lack of alternatives. Research has repeatedly demonstrated the harm of obstetric evacuation, causing emotional, physical, and financial stress for pregnant and postpartum Indigenous women and people. Our objective was to describe the costs of obstetric evacuation, as reported in the literature. METHODS: We conducted a systematic review using online searches of electronic databases (Ovid EMBASE, CINAHL, Ovid Healthstar, PubMed, ScienceDirect, PROSPERO, and Cochrane Database of Systematic Reviews) and identified studies that reported costs related to medical evacuation or transportation in rural and remote Indigenous communities. We performed critical appraisal of relevant studies. SYNTHESIS: We identified 19 studies that met the inclusion criteria. The studies reported various types of cost, including direct, indirect, and intangible costs. Medical evacuation costs ranged from CAD $7714 to CAD $31,794. Indirect and intangible costs were identified, including lost income and lack of respect for cultural practices. CONCLUSION: Costs associated with obstetric evacuation are high, with medical evacuation as the most expensive direct cost identified. Although we were able to identify a range of costs, information on financing and funding flows was unclear. Across Canada, additional research is required to understand the direct costs of obstetric evacuation to Indigenous Peoples and communities.

RéSUMé: OBJECTIF: Une ligne directrice oblige les personnes inuites et des Premières Nations vivant dans des réserves ou des régions rurales et isolées et qui en sont entre leur 36e et leur 38e semaine de grossesse à se rendre dans un centre urbain pour y attendre le travail et l'accouchement. Bien qu'elle ne soit pas enchâssée dans la loi canadienne, cette ligne directrice (et le principe qu'elle cache) est renforcée par l'absence de solutions de rechange. Des études ont démontré à maintes reprises les préjudices de l'évacuation obstétricale, qui cause un stress émotionnel, physique et financier pour les femmes et les personnes enceintes autochtones en période postpartum. Nous avons cherché à décrire les coûts de l'évacuation obstétricale figurant dans la littérature spécialisée. MéTHODE: Nous avons mené une revue systématique en consultant des bases de données électroniques (Ovid EMBASE, CINAHL, Ovid Healthstar, PubMed, ScienceDirect, PROSPERO et Cochrane Database of Systematic Reviews), puis en répertoriant les études faisant état des coûts de l'évacuation médicale ou du transport médical dans les communautés autochtones rurales et éloignées. Nous avons ensuite effectué une évaluation critique des études pertinentes. SYNTHèSE: Dix-neuf études répondaient aux critères d'inclusion. Elles faisaient état de divers types de coûts : directs, indirects et intangibles. Les coûts de l'évacuation médicale variaient de 7 714 $ à 31 794 $ CAN. Les coûts indirects et intangibles identifiés étaient la perte de revenu et le manque de respect pour les pratiques culturelles. CONCLUSION: Les coûts associés à l'évacuation obstétricale sont importants, et le coût direct le plus élevé est celui de l'évacuation médicale. Nous avons été en mesure de cerner une fourchette de coûts, mais les informations sur le financement et les flux de financement n'étaient pas claires. Partout au Canada, il faudrait pousser la recherche pour connaître les coûts directs de l'évacuation obstétricale pour les personnes et les communautés autochtones.

Infant Microbiota Communities and Human Milk Oligosaccharide Supplementation Independently and Synergistically Shape Metabolite Production and Immune Responses in Healthy Mice.

BACKGROUND: Multiple studies have demonstrated associations between the early-life gut microbiome and incidence of inflammatory and autoimmune disease in childhood. Although microbial colonization is necessary for proper immune education, it is not well understood at a mechanistic level how specific communities of bacteria promote immune maturation or drive immune dysfunction in infancy. OBJECTIVES: In this study, we aimed to assess whether infant microbial communities with different overall structures differentially influence immune and gastrointestinal development in healthy mice. METHODS: Germ-free mice were inoculated with fecal slurries from Bifidobacterium longum subspecies infantis positive (BIP) or B. longum subspecies infantis negative (BIN) breastfed infants; half of the mice in each group were also supplemented with a pool of human milk oligosaccharides (HMOs) for 14 d. Cecal microbiome composition and metabolite production, systemic and mucosal immune outcomes, and intestinal morphology were assessed at the end of the study. RESULTS: The results showed that inoculation with a BIP microbiome results in a remarkably distinct microbial community characterized by higher relative abundances of cecal Clostridium senu stricto, Ruminococcus gnavus, Cellulosilyticum sp., and Erysipelatoclostridium sp. The BIP microbiome produced 2-fold higher concentrations of cecal butyrate, promoted branched short-chain fatty acid (SCFA) production, and further modulated serotonin, kynurenine, and indole metabolism relative to BIN mice. Further, the BIP microbiome increased the proportions of innate and adaptive immune cells in spleen, while HMO supplementation increased proliferation of mesenteric lymph node cells to phorbol myristate acetate and lipopolysaccharide and increased serum IgA and IgG concentrations. CONCLUSIONS: Different microbiome compositions and HMO supplementation can modulate SCFA and tryptophan metabolism and innate and adaptive immunity in young, healthy mice, with potentially important implications for early childhood health.

Gut microbiome in the first 1000 days and risk for childhood food allergy.

OBJECTIVE: To summarize recent data on the association between gut microbiome composition and food allergy (FA) in early childhood and highlight potential host-microbiome interactions that reinforce or abrogate oral tolerance. DATA SOURCES: PubMed search of English-language articles related to FA, other atopic disease, and the gut microbiome in pregnancy and early childhood. STUDY SELECTIONS: Human studies published after 2015 assessing the relationship between the gut bacteriome and virome in the first 2 years of life and FA or food sensitization development in early childhood were prioritized. Additional human studies conducted on the prenatal gut microbiome or other atopic diseases and preclinical studies are also discussed. RESULTS: Children who developed FA harbored lower abundances of Bifidobacterium and Clostridia species and had a less mature microbiome during infancy. The early bacterial microbiome protects against FA through production of anti-inflammatory metabolites and induction of T regulatory cells and may also affect FA risk through a role in trained immunity. Infant enteric phage communities are related to childhood asthma development, though no data are available for FA. Maternal gut microbiome during pregnancy is associated with childhood FA risk, potentially through transplacental delivery of maternal bacterial metabolites, though human studies are lacking. CONCLUSION: The maternal and infant microbiomes throughout the first 1000 days of life influence FA risk through a number of proposed mechanisms. Further large, longitudinal cohort studies using taxonomic, functional, and metabolomic analysis of the bacterial and viral microbiomes are needed to provide further insight on the host-microbe interactions underlying FA pathogenesis in childhood.

A Murine Model for Measuring Sebum Production That Can Be Used to Test Therapeutic Agents for the Management of Acne Vulgaris.

Acne vulgaris (acne) effects nearly 90% of all Western teenagers, and the only pharmaceutical class of agents to treat severe forms of this skin condition are the retinoids, which are well-described teratogens. Yet about 50% of the patients receiving this class of therapeutics are women of child-bearing age, in their peak years of reproductive potential. On this basis, there is a significant unmet medical need for agents to treat severe forms of acne that do not carry this liability. As a means to assess potential agents of this type, here we describe methods for estimating the relative amount of sebum that a mouse produces based on the water retention on fur following a thorough wetting procedure. We have shown that a compound that is clinically effective in reducing sebum production demonstrates activity in this model. The method is therefore useful for evaluating therapeutic candidates for reducing sebum production, which would in turn be useful for treating acne. We have broken the entire procedure down into two phases/two protocols, as listed below. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Pre-wash wet weight measurement Basic Protocol 2: Post-wash wet-weight measurement.

Stressed and Depressed: Prevalence of Anxiety and/or Depression in Physician Assistant Students.

INTRODUCTION: This research highlights the prevalence of anxiety and/or depression among physician assistant (PA) students compared with the general population. It is believed that the results of this study will encourage graduate programs to place a stronger emphasis on the mental health of students and create a more positive learning environment. METHODS: An original survey was created using questions from Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and several original questions. The survey was distributed using a SurveyMonkey link to directors of all accredited US PA programs. Program directors were asked to distribute the survey to their students. The survey remained open for 6 weeks, after which a cross-sectional statistical analysis was performed to compare the results with national anxiety and depression data in the United States. RESULTS: There is a statistically significant increase in the rate of occurrence of anxiety and/or depression among PA students compared with the general population. According to survey results, 84.4% of respondents experienced feelings of anxiety and 80.9% experienced feelings of depression while enrolled in PA school. Physician assistant students found the greatest need for anxiety and depression treatment during the didactic portion of their program. DISCUSSION: When compared with the national population, the level of anxiety in PA students was found to be 65.3% higher and the levels of depression in PA students to be 72.5% higher. These results should encourage PA programs and health care providers to take action regarding the mental health of future providers.

Nonpharmacological tactile activity interventions for reducing behavioural and psychological symptoms of dementia in the acute hospital setting: An integrative review.

AIM: To review existing research on nonpharmacological tactile activity interventions for reducing behavioural and psychological symptoms of dementia in the acute hospital setting. BACKGROUND: When people living with dementia are admitted to hospital, they often experience an exacerbation of behavioural and psychological symptoms of dementia. Pharmacological interventions are often used to manage behavioural and psychological symptoms of dementia despite the low success rate and the heightened risk of morbidity and mortality. Low-cost alternatives that are implementable at the bedside are nonpharmacological interventions such as tactile activity interventions. DESIGN: An integrative review of the literature. METHODS: Four databases were searched using the PRISMA framework to guide the search and screening. Eligible studies were identified and the quality of each was evaluated using the Mixed Method Appraisal Tool. Thematic analysis was conducted to identify and analyse key themes across all articles. The PRISMA checklist was used to evaluate the current study. RESULTS: Seven studies examined the use of tactile activity interventions to reduce the behavioural and psychological symptoms of dementia and the barriers and facilitators to implementation. CONCLUSION: There is limited evidence exploring tactile activity interventions for reducing behavioural and psychological symptoms of dementia in acute hospital settings. Individualised approaches in combination with staffing expertise appear central to implementation. RELEVANCE TO CLINICAL PRACTICE: Acute hospital settings can result in increased behavioural and psychological symptoms of dementia which can be distressing for patients and family and challenging for nursing staff. Tactile activity interventions may offer a low resource bedside option to support people with dementia in acute health settings. PATIENT OR PUBLIC CONTRIBUTION: No direct patient or public contribution to the review.

Effects of a True Prophylactic Treatment on Hippocampal and Amygdala Synaptic Plasticity and Gene Expression in a Rodent Chronic Stress Model of Social Defeat.

Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory-e.g., the amygdala and hippocampus-are dysregulated in PTSD, the pathophysiology of the disorder is not well defined and therefore, pharmacological interventions are extremely limited. Because stress hormones norepinephrine and cortisol (corticosterone in rats) are heavily implicated in the disorder, we explored whether preemptively and systemically antagonizing ß-adrenergic and glucocorticoid receptors with propranolol and mifepristone are sufficient to mitigate pathological changes in synaptic plasticity, gene expression, and anxiety induced by a modified social defeat (SD) stress protocol. Young adult, male Sprague Dawley rats were initially pre-screened for anxiety. The rats were then exposed to SD and chronic light stress to induce anxiety-like symptoms. Drug-treated rats were administered propranolol and mifepristone injections prior to and continuing throughout SD stress. Using competitive ELISAs on plasma, field electrophysiology at CA1 of the ventral hippocampus (VH) and the basolateral amygdala (BLA), quantitative RT-PCR, and behavior assays, we demonstrate that our SD stress increased anxiety-like behavior, elevated long-term potentiation (LTP) in the VH and BLA, and altered the expression of mineralocorticoid, glucocorticoid, and glutamate receptors. These measures largely reverted to control levels with the administration of propranolol and mifepristone. Our findings indicate that SD stress increases LTP in the VH and BLA and that prophylactic treatment with propranolol and mifepristone may have the potential in mitigating these and other stress-induced effects.

Intermacs quarterly report analysis to monitor longitudinal outcomes in a centrifugal flow assist device.

In June 2021, HVAD System distribution ceased due to observational data demonstrating increased mortality and neurological events compared to another commercial device, and a device malfunction with delay or failure to restart, especially in certain subpopulations. To assess ongoing risk for patients on support following subsequent device recalls, the manufacturer's Intermacs HVAD System 2022 Quarterly Reports were queried to identify mortality and adverse events trends in a contemporary cohort of 3110 primary HVAD implantations since October 2017, stratified by year-of-implant. Mean duration of support was 21 ± 16 months, with 33% alive on original device, 25% transplanted, 6% undergoing device exchange, 4% recovered, and 32% expired. Kaplan-Meier and event-per-patient-year estimates for survival, freedom from device explant, stroke, and pump thrombus were similar across year-of-implant. Following market withdrawal and recent device recalls, there appears to be no increase in mortality, stroke, pump thrombus, or explant for HVAD-supported patients. Quarterly report monitoring is ongoing.

Thyrotoxic Periodic Paralysis With Hypokalemia: A Case Study.

Thyrotoxic periodic paralysis (TPP) is a rare life-threatening condition most commonly seen in individuals between the ages of 20-40 years. It is most prevalent in Hispanic and Asian populations. Here we present a case report of a young male patient admitted to our facility with an acute onset of paralysis. He was found to have new-onset hyperthyroidism and severe hypokalemia. TPP was exacerbated by the intake of a high-carbohydrate meal as well as a steroid injection within 24 hours of symptom onset.

Sex-specific biobehavioral regulation of persistent inflammatory pain by alcohol.

BACKGROUND: Although a large percentage of chronic pain patients consume alcohol to manage their pain, there is a significant gap in knowledge regarding the mechanisms underlying the antinociceptive effects of alcohol. METHODS: To determine the longitudinal analgesic effects of alcohol, we utilized the complete Freund's adjuvant (CFA) model of inflammatory pain in adult female and male Wistar rats. Both somatic and negative motivational aspects of pain were measured using the electronic von Frey (mechanical nociception) system, thermal probe test (thermal nociception), and mechanical conflict avoidance task (pain avoidance-like behavior). Tests were conducted at baseline and 1 and 3 weeks following intraplantar CFA or saline administration. At both time points post-CFA, animals were treated with each of three doses of alcohol (intraperitoneal; 0, 0.5, and 1.0 g/kg) over separate days in a Latin square design. RESULTS: Alcohol produced dose-dependent mechanical analgesia and antihyperalgesia in females but only antihyperalgesia in males. Although alcohol continued to attenuate CFA-induced decreases in both thermal and mechanical nociceptive thresholds between 1 and 3 weeks post-CFA, it appeared less effective at increasing thresholds 3 weeks after CFA induction. CONCLUSIONS: These data suggest that individuals may develop tolerance to alcohol's ability to alleviate both somatic and negative motivational symptoms of chronic pain over time. We also discovered sex-specific neuroadaptations in protein kinase A-dependent phosphorylation of GluR1 subunits and extracellular signal-regulated kinase (ERK 1/2) phosphorylation in nociceptive brain centers of animals receiving an alcohol challenge 1 week post-CFA. Together, these findings illustrate a sex-specific regulation of behavioral and neurobiological indices of persistent pain by alcohol.

Utility of preoperative urine cultures and cystoscopies before ureteral reimplantation in pediatrics.

BACKGROUND: Ureteral reimplantation remains the primary surgical method used for patients with vesicoureteral reflux (VUR). Cystoscopy is commonly performed first to visualize anatomy and rule out possible abnormalities. Urine cultures may also be obtained. The objective of this study is to evaluate the prudency of preoperative urine cultures and cystoscopies in pediatric patients undergoing ureteral reimplantation. METHODS: Pediatric urologists were surveyed regarding collecting urine cultures in asymptomatic patients and cystoscopies before reimplantation. A retrospective review was also conducted of patients who underwent ureteral reimplantation for VUR between March 2018 and April 2021 at Cook Children's Medical Center. RESULTS: When physicians were asked the frequency they obtain urine cultures before reimplantation on asymptomatic patients, 36% said "never" and 38% said "always." Regarding cystoscopy, 53% said "never" and 32% said "always." Inclusion criteria were met by 101 patients. Cystoscopies were performed in 46 patients and never altered the reimplantation. There were 20 preoperative, 90 intraoperative, and 61 postoperative urine cultures. Complications were associated with positive cultures of urine collected intraoperatively and postoperatively only. CONCLUSION: Cystoscopies and asymptomatic urine cultures obtained before ureteral reimplantation provide no additional benefit while increasing cost for patients' families. Further research is needed to thoroughly identify the prudency of such practices in ureteral reimplantation for VUR.

Agmatine reduces alcohol drinking and produces antinociceptive effects in rodent models of alcohol use disorder.

Alcohol use disorder (AUD) is a chronic, relapsing disorder characterized by an escalation of drinking and the emergence of negative affective states over time. Within this framework, alcohol may be used in excessive amounts to alleviate withdrawal-related symptoms, such as hyperalgesia. Future effective therapeutics for AUD may need to exhibit the ability to reduce drinking as well as to alleviate co-morbid conditions such as pain, and to take mechanistic sex differences into consideration. Agmatine is an endogenous neuromodulator that has been previously implicated in the regulation of reward and pain processing. In the current set of studies, we examined the ability of agmatine to reduce escalated ethanol drinking in complementary models of AUD where adult male and female mice and rats were made dependent via chronic, intermittent ethanol vapor exposure (CIE). We also examined the ability of agmatine to modify thermal and mechanical sensitivity in alcohol-dependent male and female rats. Agmatine reduced alcohol drinking in a dose-dependent fashion, with somewhat greater selectivity in alcohol-dependent female mice (versus non-dependent female mice), but equivalent efficacy across male mice and both groups of male and female rats. In mice and female rats, this efficacy did not extend to sucrose drinking, indicating some selectivity for ethanol reinforcement. Female rats made dependent on alcohol demonstrated significant hyperalgesia symptoms, and agmatine produced dose-dependent antinociceptive effects across both sexes. While additional mechanistic studies into agmatine are necessary, these findings support the broad-based efficacy of agmatine to treat co-morbid excessive drinking and pain symptoms in the context of AUD.

Utilization of the emergency department as a routine source of care among children with asthma.

Objective: To describe characteristics of children with persistent asthma in the ED who receive most of their healthcare in emergency settings; and determine whether recent asthma experiences or historic patterns of care are associated with identifying the ED as a typical location for care.Methods: We conducted a sub-analysis of baseline data from Telemedicine Enhanced Asthma Management through the Emergency Department (TEAM-ED), an RCT of children (3-12 years) presenting to the ED with persistent asthma (2016-2020). Caregivers identified reasons for seeking emergency care, including if their child received most overall healthcare in the ED ('ED Care'; primary outcome) or not ('Other Care'). Independent variables included demographics, recent symptoms and quality of life (QOL), and historic preventive care and healthcare use. We compared responses between ED Care and Other Care groups using bivariate and multivariate analyses.Results: We analyzed data for 355 children (31% ED Care, 69% Other Care). Compared with Other Care, ED Care respondents were more likely to identify the ED as the closest source of healthcare; report fewer symptom nights but a poorer quality of life; and describe the ED as a usual place for sick care, despite most having a PCP.Conclusions: Many children with asthma use the ED as a typical source of healthcare, and are distinguished by need for proximity, poorer caregiver QOL, and historic patterns of care-seeking. Efforts to improve timely access to outpatient care and reinforce the role of PCP-directed asthma management, such as through telemedicine, may reduce preventable morbidity including ED visits.

Reproductive coercion as a form of family violence against immigrant and refugee women in Australia.

Reproductive coercion (RC), generally considered a form of intimate partner violence (IPV), refers to perpetrator behaviours and actions that are intended to interfere with and control the autonomous decision-making of a person regarding their reproductive health. To date there are few studies that document RC as experienced by immigrant and refugee women. In this article, we explore cases of RC as described by women who were part of a larger qualitative study investigating violence against immigrant and refugee women in southern Australia. The study aimed to identify the types of RC detailed in immigrant and refugee women's narratives, and to illustrate the contexts in which these experiences occurred. Analysis followed Baxter and Jack's (2008) case study methodology; whereby particular "cases" are used to describe a phenomenon in context. Thirteen women from seven countries described experiences that fit definitions of RC. The cases describe various types of RC including violence during pregnancy with the intent of causing miscarriage, forced abortion, contraception sabotage and forced pregnancy. As well as intimate partners, some women described multiple perpetrators being complicit in their experience of RC, especially in regard to controlling women's access to, and interactions with health services. More information is needed about immigrant and refugee women's experiences of RC, and how vulnerability to multi-perpetrator violence affects health service access. In particular knowledge about how multi-perpetrator RC can affect consent processes for women who already face barriers to health care requires attention. Further research is required to address knowledge gaps about appropriate prevention and advocacy work about RC in refugee and migrant communities, and what training is needed for professionals in the family violence sector, women's health services, women's organisations, multicultural and ethno-specific services.

Gut microbiome and breast-feeding: Implications for early immune development.

Establishment of the gut microbiome during early life is a complex process with lasting implications for an individual's health. Several factors influence microbial assembly; however, breast-feeding is recognized as one of the most influential drivers of gut microbiome composition during infancy, with potential implications for function. Differences in gut microbial communities between breast-fed and formula-fed infants have been consistently observed and are hypothesized to partially mediate the relationships between breast-feeding and decreased risk for numerous communicable and noncommunicable diseases in early life. Despite decades of research on the gut microbiome of breast-fed infants, there are large scientific gaps in understanding how human milk has evolved to support microbial and immune development. This review will summarize the evidence on how breast-feeding broadly affects the composition and function of the early-life gut microbiome and discuss mechanisms by which specific human milk components shape intestinal bacterial colonization, succession, and function.

Assessing urinary phenol and paraben mixtures in pregnant women with and without gestational diabetes mellitus: A case-control study.

Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable logistic regression was used to evaluate the associations between individual chemical biomarkers and GDM while controlling for confounding. We used probit implementation of BKMR with hierarchical variable selection to estimate the mean difference in GDM probability for each component of the phenol and paraben mixtures while controlling for the correlation among the chemical biomarkers. When analyzing individual chemicals using logistic regression, benzophenone-3 was positively associated with GDM [adjusted odds ratio (aOR) per interquartile range (IQR) = 1.54, 95% confidence interval (CI) 1.15, 2.08], while BPA was negatively associated with GDM (aOR 0.61, 95% CI 0.37, 0.99). In probit-BKMR analysis, an increase in z-score transformed log urinary concentrations of benzophenone-3 from the 10th to 90th percentile was associated with an increase in the estimated difference in the probability of GDM (0.67, 95% Credible Interval 0.04, 1.30), holding other chemicals fixed at their medians. No associations were identified between other chemical biomarkers and GDM in the BKMR analyses. We observed that the association of BPA and GDM was attenuated when accounting for correlated phenols and parabens, suggesting the importance of addressing chemical mixtures in perinatal environmental exposure studies. Additional prospective investigations will increase the understanding of the relationship between benzophenone-3 exposure and GDM development.

Biomarkers of Development of Immunity and Allergic Diseases in Farming and Non-farming Lifestyle Infants: Design, Methods and 1 Year Outcomes in the "Zooming in to Old Order Mennonites" Birth Cohort Study.

Traditional farming lifestyle has been shown to be protective against asthma and allergic diseases. The individual factors that appear to be associated with this "farm-life effect" include consumption of unpasteurized farm milk and exposure to farm animals and stables. However, the biomarkers of the protective immunity and those associated with early development of allergic diseases in infancy remain unclear. The "Zooming in to Old Order Mennonites (ZOOM)" study was designed to assess the differences in the lifestyle and the development of the microbiome, systemic and mucosal immunity between infants born to traditional farming lifestyle at low risk for allergic diseases and those born to urban/suburban atopic families with a high risk for allergic diseases in order to identify biomarkers of development of allergic diseases in infancy. 190 mothers and their infants born to Old Order Mennonite population protected from or in Rochester families at high risk for allergic diseases were recruited before birth from the Finger Lakes Region of New York State. Questionnaires and samples are collected from mothers during pregnancy and after delivery and from infants at birth and at 1-2 weeks, 6 weeks, 6, 12, 18, and 24 months, with 3-, 4-, and 5-year follow-up ongoing. Samples collected include maternal blood, stool, saliva, nasal and skin swabs and urine during pregnancy; breast milk postnatally; infant blood, stool, saliva, nasal and skin swabs. Signs and symptoms of allergic diseases are assessed at every visit and serum specific IgE is measured at 1 and 2 years of age. Allergic diseases are diagnosed by clinical history, exam, and sensitization by skin prick test and/or serum specific IgE. By the end of the first year of life, the prevalence of food allergy and atopic dermatitis were higher in ROC infants compared to the rates observed in OOM infants as was the number of infants sensitized to foods. These studies of immune system development in a population protected from and in those at risk for allergic diseases will provide critical new knowledge about the development of the mucosal and systemic immunity and lay the groundwork for future studies of prevention of allergic diseases.

Microbial Interrelationships across Sites of Breastfeeding Mothers and Infants at 6 Weeks Postpartum.

Infancy is a critical life stage for the establishment of the gut microbiome. Human milk contains a unique microbial ecosystem that serves as a continuous source of commensal bacteria for the infant. However, the origin of the human milk microbiota, how it is influenced by breastfeeding exclusivity, and its role in infant gut microbiota assembly are not clear. To interrogate these questions, we examined the relationships among fecal, oral, breast skin, and human milk microbiota of 33 exclusively breastfeeding (EBF) and mixed-feeding (MF; human milk + infant formula) mother-infant pairs at 6 weeks postpartum. Here, we show that MF infants have a significantly more diverse oral microbiome comprised of lower relative abundances of Streptococcus and Gemella and higher abundances of Veillonella. Using both SourceTracker2 and FEAST, we demonstrate breast skin and infant saliva as the principal contributing sources to the human milk microbiota. Of the sampled sites, human milk and maternal stool were predicted to contribute the largest fraction to the infant fecal microbiome, but the majority of the community was estimated to arise from unknown sources. Lastly, we identified twenty-one significant co-occurrence relationships between bacteria in human milk and on other maternal and infant body sites. These results demonstrate several unique microbial interrelationships between breastfeeding dyads, providing insight into potential mechanisms of microbial assembly in early life.