Study protocol for the ABERRANT study: antibiotic-induced disruption of the maternal and infant microbiome and adverse health outcomes - a prospective cohort study among children born at term.

INTRODUCTION: There is compositional overlap between the maternal intestinal microbiome, the breast milk microbiome and the infant oral and intestinal microbiome. Antibiotics cause profound changes in the microbiome. However, the effect of intrapartum and early-life antibiotics on the maternal intestinal and breast milk microbiome, and the infant oral and intestinal microbiome, and whether effects are only short term or persist long term remain uncertain. METHODS AND ANALYSES: In this prospective cohort study, we will use metagenomic sequencing to determine: (1) the effect of intrapartum antibiotics on the composition of the breast milk, and the infant oral and intestinal microbiome, including the development and persistence of antibiotic resistance; (2) the effect of antibiotic exposure in the first year of life on the composition of the infant oral and intestinal microbiome, including the development and persistence of antibiotic resistance; (3) the effect of disruption of the infant oral and intestinal microbiome on health outcomes and (4) the compositional overlap between the maternal intestinal microbiome, the breast milk microbiome and the infant oral and intestinal microbiome. ETHICS AND DISSEMINATION: The ABERRANT study has been approved by the commission cantonale d'éthique de la recherche sur l'être humain (CER-VD) du Canton de Vaud (#2019-01567). Outcomes will be disseminated through publication and will be presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04091282.

Pediatricians' affective communication behavior attenuates parents' stress response during the medical interview.

OBJECTIVE: To investigate whether the medical interview in the pediatric context generates a stressful response in parents in form of heightened cortisol activity, and whether pediatricians' empathetic communication is able to attenuate this stress response. METHODS: 68 parents were recruited at pediatric out-patient and in-patient consultations. Salivary samples were collected between 60 and 30min prior to the consultation, shortly before the consultation, 20min as well as 45min after the consultation. 19 pediatricians participated in the study and effectuated the medical visit as usual. We videotaped the consultations and coded pediatricians' affective communication using the RIAS and the Four Habits Coding Scheme. RESULTS: Parents' cortisol increased during the medical visit with a peak at 20min after the medical encounter. Furthermore, multilevel analysis revealed a lesser increase in parents' cortisol response associated with pediatricians' levels in supportive communication behaviors. CONCLUSION: As indicated by their humoral stress responses, the medical encounter was stressful for the parents. Pediatricians' affective communication modulated this stress response in that more supportive communication was related to smaller cortisol increases. PRACTICE IMPLICATION: Pediatricians' affective communication behavior during the medical visit can alleviate parents' distress and anxiety, representing a source of social and emotional support.

Brain catecholamine depletion and motor impairment in a Th knock-in mouse with type B tyrosine hydroxylase deficiency.

Tyrosine hydroxylase catalyses the hydroxylation of L-tyrosine to l-DOPA, the rate-limiting step in the synthesis of catecholamines. Mutations in the TH gene encoding tyrosine hydroxylase are associated with the autosomal recessive disorder tyrosine hydroxylase deficiency, which manifests phenotypes varying from infantile parkinsonism and DOPA-responsive dystonia, also termed type A, to complex encephalopathy with perinatal onset, termed type B. We generated homozygous Th knock-in mice with the mutation Th-p.R203H, equivalent to the most recurrent human mutation associated with type B tyrosine hydroxylase deficiency (TH-p.R233H), often unresponsive to l-DOPA treatment. The Th knock-in mice showed normal survival and food intake, but hypotension, hypokinesia, reduced motor coordination, wide-based gate and catalepsy. This phenotype was associated with a gradual loss of central catecholamines and the serious manifestations of motor impairment presented diurnal fluctuation but did not improve with standard l-DOPA treatment. The mutant tyrosine hydroxylase enzyme was unstable and exhibited deficient stabilization by catecholamines, leading to decline of brain tyrosine hydroxylase-immunoreactivity in the Th knock-in mice. In fact the substantia nigra presented an almost normal level of mutant tyrosine hydroxylase protein but distinct absence of the enzyme was observed in the striatum, indicating a mutation-associated mislocalization of tyrosine hydroxylase in the nigrostriatal pathway. This hypomorphic mouse model thus provides understanding on pathomechanisms in type B tyrosine hydroxylase deficiency and a platform for the evaluation of novel therapeutics for movement disorders with loss of dopaminergic input to the striatum.

Physiologie der Sexualhormone bei Mann und Frau.

The biosynthesis of steroid hormones is a fascinating process . In this reaction cascade, cholesterol, a normal constituent of the lipid membrane bylayers, is coverted through a number of hydroylation, oxidation and reduction steps into a variety of biologically active substances, such as mineralocorticoids, glucocorticoids and sex hormones. Most of these modifications take place in the adrenal glands, testes and ovaries, although other tissues such as liver, kidney, placenta, brain, and skin are also quite active. The effect of steroid hormones is a complex, not yet fully understood process in which steroid hormones bind to specific intracellular receptors in the target cells, so that interactions with DNA in the nucleus are possible. What follows is a modulation of gene activity and a hormone- specific reaction occurs (1). Physiologically, sex hormones are important in every stage of life, from determining the sex differentiation, to the phenotypic differentiation in a female or male individual. They are also essential for a successful reproductive life and are involved in the development of the brain and the expression of gender specific behavior. Anomalies in each step of steroid hormone action have potential clinical consequences. Abnormalities in the receptor or post-receptor machinery lead to disturbances of the effect of a particular hormone. However, abnormalities of steroid hormone production can also lead to serious and complex effects. For example,the consequences of a block in the steroid synthesis ate twp-fold: on the one hand the lack of products has dramatic consequences in the development and function of the target organs; on the other hand the accumulation of the hormone upstream the block will cause the activation of other members of the steroid hormone receptor family. Both conditions can cause complex clinical pictures.