Bisphenol A and its analogues: A comprehensive review to identify and prioritize effect biomarkers for human biomonitoring

Human biomonitoring (HBM) studies have demonstrated widespread and daily exposure to bisphenol A (BPA). Moreover, BPA structural analogues (e.g. BPS, BPF, BPAF), used as BPA replacements, are being increasingly detected in human biological matrices. BPA and some of its analogues are classified as endocrine disruptors suspected of contributing to adverse health outcomes such as altered reproduction and neurodevelopment, obesity, and metabolic disorders among other developmental and chronic impairments. One of the aims of the H2020 European Human Biomonitoring Initiative (HBM4EU) is the implementation of effect biomarkers at large scales in future HBM studies in a systematic and standardized way, in order to complement exposure data with mechanistically-based biomarkers of early adverse effects. This review aimed to identify and prioritize existing biomarkers of effect for BPA, as well as to provide relevant mechanistic and adverse outcome pathway (AOP) information in order to cover knowledge gaps and better interpret effect biomarker data. A comprehensive literature search was performed in PubMed to identify all the epidemiologic studies published in the last 10 years addressing the potential relationship between bisphenols exposure and alterations in biological parameters. A total of 5716 references were screened, out of which, 119 full-text articles were analyzed and tabulated in detail. This work provides first an overview of all epigenetics, gene transcription, oxidative stress, reproductive, glucocorticoid and thyroid hormones, metabolic and allergy/immune biomarkers previously studied. Then, promising effect biomarkers related to altered neurodevelopmental and reproductive outcomes including brainderived neurotrophic factor (BDNF), kisspeptin (KiSS), and gene expression of nuclear receptors are prioritized, providing mechanistic insights based on in vitro, animal studies and AOP information. Finally, the potential of omics technologies for biomarker discovery and its implications for risk assessment are discussed. To the best of our knowledge, this is the first effort to comprehensively identify bisphenol-related biomarkers of effect for HBM purposes.European Union Commission H2020-EJP-HBM4EU 733032HBM4EU Initiativ

Airway reconstruction in children

Aim/Background : Airway anomalies are infrequent but potentially life threatening in children. A program to care for these difficult children was set up at our institution, and this paper summarizes our experience. Methods: A total of 34 children were enrolled in the program over a period of three years. These children were evaluated as per the standard protocols. Treatment was individualized. Results: Of these 34 children, 28 had their airways restored and are doing well. Four children continue to remain on tracheostomy and two will require long term tracheostomy. There were two deaths. All children are under surveillance as there is a risk of recurrence. Conclusions: Airway anomalies are complex problems with significant morbidity and mortality. Current therapeutic modalities allow for good results. Most children were successfully decannulated and did well

Live births after embryo selection using morphokinetics versus conventional morphology: a retrospective analysis

The increasing corpus of clinical studies using time-lapse imaging for embryo selection demonstrates considerable variation in study protocols and only limited-sized study cohorts. Outcome measures are based on implantation or clinical pregnancy; some predict blastulation from early cleavage-stage data, and few have evaluated live birth. Erroneously, most studies treat the embryos as independent variables and do not include patient or treatment variables in the statistical analyses. In this study, cohort size was 14,793 patients and 23,762 cycles. The incidence of live birth (n = 973 deliveries) after embryo selection by objective morphokinetic algorithms was compared with conventional embryology selection parameters (n = 6948 deliveries). A 19% increase in the incidence of live birth was observed when morphokinetic data were used to select embryos for the patient cohort aged younger than 38 years (OR 1.19 with 95% CI 1.06 to 1.34) using their own eggs, and an increase of 37% for oocyte recipients aged over 37 years (OR 1.370; 95% Cl 0.763 to 2.450). This is the largest study of the prospective use of time-lapse imaging algorithms in IVF reporting on live birth outcome, although the nature of purely a closed system versus standard incubation could not be assessed

The Lysophosphatidylcholine Transporter MFSD2A Is Essential for CD8(+) Memory T Cell Maintenance and Secondary Response to Infection

10.4049/jimmunol.1801585JOURNAL OF IMMUNOLOGY2031117-12