The Bern Birth Cohort (BeBiCo) to study the development of the infant intestinal microbiota in a high-resource setting in Switzerland: rationale, design, and methods.

BACKGROUND: Microbiota composition is fundamental to human health with the intestinal microbiota undergoing critical changes within the first two years of life. The developing intestinal microbiota is shaped by maternal seeding, breast milk and its complex constituents, other nutrients, and the environment. Understanding microbiota-dependent pathologies requires a profound understanding of the early development of the healthy infant microbiota. METHODS: Two hundred and fifty healthy pregnant women (≥20 weeks of gestation) from the greater Bern area will be enrolled at Bern University hospital's maternity department. Participants will be followed as mother-baby pairs at delivery, week(s) 1, 2, 6, 10, 14, 24, 36, 48, 96, and at years 5 and 10 after birth. Clinical parameters describing infant growth and development, morbidity, and allergic conditions as well as socio-economic, nutritional, and epidemiological data will be documented. Neuro-developmental outcomes and behavior will be assessed by child behavior checklists at and beyond 2 years of age. Maternal stool, milk, skin and vaginal swabs, infant stool, and skin swabs will be collected at enrolment and at follow-up visits. For the primary outcome, the trajectory of the infant intestinal microbiota will be characterized by 16S and metagenomic sequencing regarding composition, metabolic potential, and stability during the first 2 years of life. Secondary outcomes will assess the cellular and chemical composition of maternal milk, the impact of nutrition and environment on microbiota development, the maternal microbiome transfer at vaginal or caesarean birth and thereafter on the infant, and correlate parameters of microbiota and maternal milk on infant growth, development, health, and mental well-being. DISCUSSION: The Bern birth cohort study will provide a detailed description and normal ranges of the trajectory of microbiota maturation in a high-resource setting. These data will be compared to data from low-resource settings such as from the Zimbabwe-College of Health-Sciences-Birth-Cohort study. Prospective bio-sampling and data collection will allow studying the association of the microbiota with common childhood conditions concerning allergies, obesity, neuro-developmental outcomes , and behaviour. Trial registration The trial has been registered at www. CLINICALTRIALS: gov , Identifier: NCT04447742.

Maternal Microbiota, Early Life Colonization and Breast Milk Drive Immune Development in the Newborn.

The innate immune system is the oldest protection strategy that is conserved across all organisms. Although having an unspecific action, it is the first and fastest defense mechanism against pathogens. Development of predominantly the adaptive immune system takes place after birth. However, some key components of the innate immune system evolve during the prenatal period of life, which endows the newborn with the ability to mount an immune response against pathogenic invaders directly after birth. Undoubtedly, the crosstalk between maternal immune cells, antibodies, dietary antigens, and microbial metabolites originating from the maternal microbiota are the key players in preparing the neonate's immunity to the outer world. Birth represents the biggest substantial environmental change in life, where the newborn leaves the protective amniotic sac and is exposed for the first time to a countless variety of microbes. Colonization of all body surfaces commences, including skin, lung, and gastrointestinal tract, leading to the establishment of the commensal microbiota and the maturation of the newborn immune system, and hence lifelong health. Pregnancy, birth, and the consumption of breast milk shape the immune development in coordination with maternal and newborn microbiota. Discrepancies in these fine-tuned microbiota interactions during each developmental stage can have long-term effects on disease susceptibility, such as metabolic syndrome, childhood asthma, or autoimmune type 1 diabetes. In this review, we will give an overview of the recent studies by discussing the multifaceted emergence of the newborn innate immune development in line with the importance of maternal and early life microbiota exposure and breast milk intake.

One in seven Swiss physicians has left patient care - results from a national cohort study from 1980-2009.

AIMS OF THE STUDY: Physician shortage is problematic, but the percentage of physicians who left patient care in Switzerland is unclear. We set out to describe this percentage and determine whether gender or language region was associated with leaving patient care. METHODS: We analysed the National Registry (Medreg) of all physicians who graduated between 1980 and 2009 in Switzerland. Based on the last known working status noted in Medreg, physicians were classified as “probably involved in patient care” or “potentially left patient care”. We drew an unrestricted random sample of 250 from each category. We searched professional directories / social media to classify each sample. Those with undetermined status received a questionnaire that asked their working status. We quantified the percentage of physicians who left patient care and used Poisson and Cox regression to determine rates and the association of leaving patient care with gender, language region, and year of graduation. RESULTS: We identified 23,112 living physicians in Medreg in 2015. Of these, 18,406 (79.6%) were probably involved in patient care and 4706 (20.4%) had potentially left patient care. In the random sample of 250 physicians probably involved in patient care, 237 were involved in patient care, 11 had left and the status of 2 was undetermined (0.8%). In the random sample of 250 physicians who had potentially left patient care, 109 were involved in patient care, 109 had left, and the status of 32 was undetermined (12.8%). We estimated that 13.6% of physicians had left patient care (95% confidence interval [CI] 11.1–16.1%). According to the most realistic scenario, the rate of physicians who had left patient care was 1.2 per 100 physicians/year (95% CI 0.9–1.6) for those who had graduated between 1980 and 1994, and 1.8 per 100 physicians/year (95% CI 1.4–2.3) for those who graduated between 1995 and 2009 (adjusted hazard ratio 1.74, 95% CI 1.12–2.71). There was no evidence that the risk of leaving patient care was associated with gender or language region. CONCLUSIONS: Approximately one in seven physicians in Switzerland who graduated between 1980 and 2009 left patient care. Leaving patient care was not associated with gender, but the probability of leaving patient care was increased considerably in physicians who graduated more recently. Interventions that aim at keeping physicians in the work force and encourage their return to practice are sorely needed.

Development of a cardiac loading device to monitor cardiac function during ex vivo graft perfusion.

BACKGROUND: Ex vivo heart perfusion systems, allowing continuous perfusion of the coronary vasculature, have recently been introduced to limit ischemic time of donor hearts prior to transplantation. Hearts are, however, perfused in an unloaded manner (via the aorta) and therefore, cardiac contractile function cannot be reliably evaluated. OBJECTIVES: We aim to develop a ventricular loading device that enables monitoring of myocardial function in an ex vivo perfusion system. In this initial study, was to develop a prototype for rat experimentation. METHODS: We designed a device consisting of a ventricular balloon and a reservoir balloon, connected through an electronic check valve, which opens and closes in coordination with changes in ventricular pressure. All balloons were produced in our laboratory and their properties, particularly pressure-volume relationships, were characterized. We developed a mock ventricle in vitro test system to evaluate the device, which was ultimately tested in ex vivo perfused rat hearts. RESULTS: Balloon production was consistent and balloon properties were maintained over time and with use on the device. Results from in vitro and ex vivo experiments show that the device functions appropriately; hemodynamic function can be measured and compares well to measurements made in an isolated, working (loaded) rat heart preparation. CONCLUSIONS: Our cardiac loading device appears to reliably allow measurement of several left ventricular hemodynamic parameters and provides the opportunity to control ventricular load.