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Background Lynch syndrome (LS) is a hereditary condition characterized by a high risk of colorectal cancer, endometrial cancer, and other neoplasia associated with germline alterations in DNA mismatch repair genes. The classical genetic diagnostic strategy for LS consists of the Sanger sequencing of genes associated with the suspected syndrome. Next-generation sequencing (NGS) enables the simultaneous sequencing of a large number of hereditary cancer genes. Here, we aimed to study whether other germline pathogenic variants of hereditary cancer genes are present in patients with LS. Methods A cohort of 84 probands with a previous genetic diagnosis of LS by Sanger sequencing was reanalyzed using NGS via a commercial panel of 94 hereditary cancer genes by hybrid capture. The American College of Medical Genetics and Genomics criteria were used to classify the clinical significance of the variants. The findings of NGS were confirmed by Sanger sequencing. When possible, genetic analyses of the new findings in the proband's relatives were also performed by Sanger sequencing. Results We identified five families (6%), out of 84, with at least two germline pathogenic variants conferring to high or moderate risk in different dominant cancer-predisposing genes: [MLH1-BRCA2-NBN], [MLH1-BRCA1], [MSH2-ATM], [MSH6-NF1], and [MLH1-FANCA]. Interestingly, only one out of these five families exhibited a clinical phenotype associated with the new pathogenic variants. The family with three pathogenic variants of the [MLH1-BRCA2-NBN] genes showed a high aggregation of tumors associated with LS and breast and ovarian cancer syndrome. Conclusions Our results showed that the co-occurrence of more than one pathogenic variant in cancer-predisposing genes was remarkable among cases of LS. In most cases, no clinicial manifestations were associated with the secondary pathogenic variants. Further studies are needed to confirm these findings and elucidate their clinical impact. Reanalysis of LS families should be considered only in families with mixed clinical phenotypes.

BACKGROUND: Adherence to the Ten Steps of the Baby-Friendly Hospital Initiative has been shown to have a protective role for the initiation and maintenance of breastfeeding. RESEARCH AIMS: (1) To determine the breastfeeding rate during the first 6 months of life in children of mothers diagnosed with COVID-19 infection at the time of birth; and (2) to assess the possible influence of being born in a center with Baby-Friendly Hospital Initiative accreditation. METHODS: This was a two-group comparative longitudinal observational study of infants born to mothers with COVID-19 at the time of birth, between March 13-May 31, 2020 (the first wave of the pandemic) in Spain. Fourteen Spanish hospitals participated, five (35.7%) were Baby-Friendly Hospital Initiative accredited. Type of feeding was assessed prospectively at discharge, 1, 3, and 6 months of age. A total of 248 newborns were included in the study. RESULTS: A total of 117 (47.3%) newborns were born in Baby-Friendly Hospital Initiative (BFHI) accredited centers. These centers applied skin-to-skin contact with greater probability (OR = 1.9; 95% CI [1.18, 3.29]) and separated the newborns from their mothers less frequently (OR = 0.46; 95% CI [0.26, 0.81]) than non-accredited centers. No differences were observed in relation to the presence of a companion at the time of birth. At discharge, 49.1% (n = 57) of newborns born in BFHI-accredited centers received exclusive breastfeeding versus 35.3% (n = 46) in non-accredited centers (p = .03). No differences were observed in breastfeeding rates throughout follow-up. CONCLUSIONS: The exclusive breastfeeding rate at discharge in children of mothers with COVID-19 infection at birth was higher in Baby-Friendly Hospital Initiative accredited centers, which most frequently applied skin-to-skin contact at birth as well as rooming-in.

Infection with SARS‐CoV2 does not spare pregnant women and the possibility of vertical transmission which might lead to fetal damages is pending. Objective We hypothesized that the observed low incidence of perinatal infection could be related to a low expression of the membrane receptor for SARS‐CoV2, ACE2, in the fetal‐placental unit. We evaluated protein expression of ACE2 both in placentas and fetal organs from non‐infected pregnancies across gestation. Methods Discovery study. Immunocytochemistry analysis for ACE2 in organs and placentas were performed in May 2020, in samples from a registered biobank. Five cases of medical termination of pregnancy performed at between 15 and 38 weeks’ in healthy women. Paraffin‐embedded tissues (kidneys, brain, lungs, intestinal tract, heart). Matching tissues from 8‐year‐old children (N=4) were tested as controls. Seven placentas including those of the 5 cases, 1 of a 7‐week miscarriage and 1 of a symptomatic SARS‐COV2 pregnancy at 34 weeks. Tissues’ sections were incubated with rabbit monoclonal anti‐ACE2. Protein expression of ACE2 was detected by immunochemistry. Results ACE2 expression was detected in fetal kidneys, rectum and ileum across gestation and similarly in the pediatric control. It was barely detectable in lungs at 15 weeks’ and not found thereafter. In the pediatric control, ACE2 was only detectable in type 2 pneumocytes. No ACE2 expression was found in the cerebral ependymal, parenchyma nor in cardiac tissues ACE2 was expressed in syncitiotrophoblast and cytotrophoblast from 7th weeks’ onwards and across gestation but not in the amnion. Similar intensity and distribution of ACE2 staining were identified in the mother's SARS‐CoV2 placenta. Conclusions Marked placental expression of ACE2 provides a rationale for vertical transmission at cellular level. Absence of ACE2 expression in the fetal brain and heart is reassuring on the risk of congenital malformation. Clinical follow‐up of infected pregnant women and their children are needed to validate these observations. This article is protected by copyright. All rights reserved.

© 2020 John Wiley & Sons, Ltd. Distributed slack bus (DSB) models for the resolution of power flow problems are a more realistic approach than the classical single slack bus concept. DSB models have been widely implemented in iterative approaches such as in Newton-Raphson power flow methods. However, iterative algorithms may lead to incorrect solutions or may fail to reach convergence under inappropriate initial estimations. The holomorphic embedding load-flow method (HELM) deals with the solution of the nonlinear power flow equations by means of complex analysis techniques, resulting in a deterministic and noniterative method, which is independent of initial estimations. As such, this paper proposes, from two different methodologies, a novel formulation and implementation of the DSB model for the HELM, which overcomes in that way the disadvantages of iterative methods and also incorporates the inherent advantages of DSB models. Moreover, this paper performs convergence and speed capability tests of the two proposed methodologies using two real-size benchmark systems.