XPC and POLH/XPV Genes Mutated in a Genetic Cluster of Xeroderma Pigmentosum Patients in Northeast Brazil

Xeroderma pigmentosum (XP) is a rare genetic condition in which exposure to sunlight leads to a high tumor incidence due to defective DNA repair machinery. Herein, we investigated seven patients clinically diagnosed with XP living in a small city, Montanhas (Rio Grande do Norte), in the Northeast region of Brazil. We performed high-throughput sequencing and, surprisingly, identified two different mutated genes. Six patients carry a novel homozygote mutation in the POLH/XPV gene, c.672_673insT (p.Leu225Serfs*33), while one patient carries a homozygote mutation in the XPC gene, c.2251-1G>C. This latter mutation was previously described in Southeastern Africa (Comoro Island and Mozambique), Pakistan, and in a high incidence in Brazil. The XP-C patient had the first symptoms before the first year of life with aggressive ophthalmologic tumor progression and a melanoma onset at 7 years of age. The XP-V patients presented a milder phenotype with later onset of the disorder (mean age of 16 years old), and one of the six XP-V patients developed melanoma at 72 years. The photoprotection is minimal among them, mainly for the XP-V patients. The differences in the disease severity between XP-C (more aggressive) and XP-V (milder) patients are obvious and point to the major role of photoprotection in the XPs. We estimate that the incidence of XP patients at Montanhas can be higher, but with no diagnosis, due to poor health assistance. Patients still suffer from the stigmatization of the condition, impairing diagnosis, education for sun protection, and medical care.

Who needs prenatal counselling with a pediatric surgeon? Experience from a large tertiary care university hospital

Objectives To describe our experience with prenatal counselling for surgical anomalies in a large volume center. The secondary aim is to suggest a list of prenatal abnormalities warranting counselling by a pediatric surgeon. Methods We reviewed all prenatal counselling consultations performed by the pediatric surgery team between January 1st, 2015 and December 31st, 2016. Results A total of 169 patients or couples had a prenatal consultation with a pediatric surgeon. Prenatal work-up included a fetal MRI in 26% of cases, mainly for digestive and thoracic pathologies (56.1% of cases). Consultation with the pediatric surgeon led mainly to recommendations concerning the place of delivery. Induction for reasons related to the fetal anomaly occurred in 22.2% of cases. Most children were surgically treated within the first year of life (63.5%). Correlation between predicted prognosis and actual status at four years of life was 96.9%. Correlation between prenatal and postnatal diagnosis was 87.4%. Conclusions Prenatal counselling by a pediatric surgeon allows couples to obtain clear information on the pathology of their unborn child, giving them greater autonomy in their decision to continue the pregnancy.

Efficacy and safety of fenfluramine in the treatment of Dravet syndrome - literature review

Dravet Syndrome is a severe, drug-resistant, and rare epileptiform disorder that is typically presented in the first year of life in an otherwise healthy child. It is characterized by prolonged seizures that are often resistant to current anti-epileptic drug regimens, which made them poorly controlled, and almost 50% of patients experience at least four tonic-clonic seizures per month. There are three new medicines: stiripentol, cannabidiol, and fenfluramine, with documented efficacy and safety as adjunctive therapies in pharmacoresistant Dravet syndrome treatment. This study aimed to assess the efficacy and safety of fenfluramine in the treatment of Dravet syndrome. Our study material consisted of publications, which were found in PubMed, Google Scholar, and Embase databases. In order to find the proper publications, the search has been conducted with the use of a combination of keywords like: “fenfluramine”, “Dravet syndrome”, “epilepsy treatment”, “Dravet syndrome pediatric patients”. The first step was to find proper publications from the last 10 years. The second step was to carry out an overview of the found publications. Results of mentioned studies proved that in Dravet syndrome, fenfluramine provided a significantly greater reduction in convulsive seizure frequency compared with placebo. No patient developed valvular heart disease or pulmonary arterial hypertension, the side effects that occurred during its use were mild and the drug was generally well-tolerated. The bioequivalence and tolerability of single oral doses of fenfluramine hydrochloride oral solution in the fed and fasted states support drug administration without regard to meals. Fenfluramine may represent a new important treatment option for Dravet syndrome.

Harmonized-Multinational qEEG Norms (HarMNqEEG)

This paper extends our frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. i) Create lifespan Hermitian Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control developmental equations for the mean and standard deviation of qEEG traditional and Hermitian Riemannian descriptive parameters were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. ii) We also show that the multinational harmonized Hermitian Riemannian norms produce z-scores with increased diagnostic accuracy to predict brain dysfunction at school-age produced by malnutrition only in the first year of life. We provide data and software for constructing norms. iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.

Visual segmentation of complex naturalistic structures in an infant eye-tracking search task

An infant's everyday visual environment is composed of a complex array of entities, some of which are well integrated into their surroundings. Although infants are already sensitive to some categories in their first year of life, it is not clear which visual information supports their detection of meaningful elements within naturalistic scenes. Here we investigated the impact of image characteristics on 8-month-olds' search performance using a gaze contingent eye-tracking search task. Infants had to detect a target patch on a background image. The stimuli consisted of images taken from three categories: vegetation, non-living natural elements (e.g., stones), and manmade artifacts, for which we also assessed target background differences in lower- and higher-level visual properties. Our results showed that larger target-background differences in the statistical properties scaling invariance and entropy, and also stimulus backgrounds including low pictorial depth, predicted better detection performance. Furthermore, category membership only affected search performance if supported by luminance contrast. Data from an adult comparison group also indicated that infants' search performance relied more on lower-order visual properties than adults. Taken together, these results suggest that infants use a combination of property- and category-related information to parse complex visual stimuli.

Genetic diversity and mate selection in a reintroduced population of gray wolves

The genetic composition of an individual can markedly affect its survival, reproduction, and ultimately fitness. As some wildlife populations become smaller, conserving genetic diversity will be a conservation challenge. Many imperiled species are already supported through population augmentation efforts and we often do not know if or how genetic diversity is maintained in translocated species. As a case study for understanding the maintenance of genetic diversity in augmented populations, I wanted to know if genetic diversity (i.e., observed heterozygosity) remained high in a population of gray wolves in the Rocky Mountains of the U.S. > 20 years after reintroduction. Additionally, I wanted to know if a potential mechanism for such diversity was individuals with below average genetic diversity choosing mates with above average diversity. I also asked whether there was a preference for mating with unrelated individuals. Finally, I hypothesized that mated pairs with above average heterozygosity would have increased survival of young. Ultimately, I found that females with below average heterozygosity did not choose mates with above average heterozygosity and wolves chose mates randomly with respect to genetic relatedness. Pup survival was not higher for mated pairs with above average heterozygosity in my models. The dominant variables predicting pup survival were harvest rate during their first year of life and years pairs were mated. Ultimately, genetic diversity was relatively unchanged > 20 years after reintroduction. The mechanism for maintaining such diversity does not appear related to individuals preferentially choosing more genetically diverse mates. Inbreeding avoidance, however, appears to be at least one mechanism maintaining genetic diversity in this population.

Language processing reveals conceptual combination in human infants

Across three eye-tracking experiments, we taught 12-month-olds (N = 60) two novel quantity labels denoting sets of one and two (e.g., “mize” for 1; “padu” for 2). We then showed that they could not only generalize these labels to sets of previously unseen objects, but also combine them with familiar category labels acquired prior to the lab visit (e.g., “ball”, “duck”). Their eye movements revealed adult-like compositional procedures that go beyond serial processing of constituent meanings. These findings indicate that certain combinatorial processes involved in extracting complex linguistic meaning are already available by the end of the first year of life and are ready to support language comprehension.

An audit of foeticide, neonaticide and infanticide: A retrospective study in the Department of Forensic Medicine, King Edward Medical University, Lahore

The deliberate killing of a foetus in the womb, or a child from the first 24 h of birth to one month of age, or within the first year of life, is called foeticide, neonaticide and infanticide, respectively. Socioeconomic stress, mental illness, gender selection, shame or fear of punishment of adultery or illegitimacy, grudge and jealousy with parents and negligent delivery by dai are major causative factors in such cases. This is a retrospective, descriptive, observational study, and the sample pool consisted of 35 cases. Foeticide cases were 42.9% of the total and the same percentage of cases were neonaticides, while 14.3% of cases were of infanticide. The male-to-female ratio was 1.26:1 and the major cause of death was head injury. The study shows a prevalence of foeticide and neonaticide as compared to infanticide. It also displays the prevalence of males in overall cases and a higher number of unknown cases in our setting.

Breastfeeding, rapid growth in the first year of life and excess weight at age 2 years: the 3D Cohort Study

Objective: To assess relationships between breastfeeding, rapid growth in the first year of life, and overweight/obesity status at age 2. Design: As part of an observational, longitudinal study beginning in early pregnancy, multivariable logistic regressions were used to assess associations between breastfeeding duration (total and exclusive) and rapid weight gain (RWG) between birth and age 1, and to determine predictors of overweight/obesity status at age 2. Setting: 9 hospitals located in the province of Quebec, Canada. Participants: 1599 term infants participating in the 3D Cohort Study Results: Children having RWG in the first year and those having excess weight at age 2 accounted for 28% and <10%, respectively. In multivariable models, children breastfed <6 months and from 6 months to <1 year were, respectively, 2.5 times (OR: 2.45; 95% CI: 1.76-3.41) and 1.8 times (OR: 1.78; 1.29-2.45) more likely to show RWG up to age 1 compared to children breastfed ≥ 1 year. Children exclusively breastfed < 3 months had significantly greater odds of RWG in the first year (OR: 1.94; 1.25-3.04) compared to children exclusively breastfed for ≥6 months. Associations between breastfeeding duration (total or exclusive) and excess weight at age 2 were not detected. RWG in the first year was found to be the main predictor of excess weight at age 2 (OR: 6.98; 4.35-11.47). Conclusions: The potential beneficial effects of breastfeeding on rate of growth in the first year of life suggest that interventions promoting breastfeeding are relevant for obesity prevention early in life.

Pediatric Urachal Anomalies: Monocentric Experience and Mini-Review of Literature

Background: Surgery is the current mainstay for the treatment of urachal anomalies (UA). Recent literature data support the theory of a spontaneous resolution within the first year of life. The aim of this study, comprising solely surgically treated children, was to identify age specific patterns regarding symptoms and outcomes that may support the non-surgical treatment of UA. Methods: Retrospective review on the clinico-laboratory characteristics of 52 children aged < 17 years undergoing resection of symptomatic UA at our pediatric surgical unit during 2006–2017. Data was dichotomized into age > 1 (n = 17) versus < 1 year (n = 35), and complicated (pre-/post-surgical abscess formation or peritonitis, n = 10) versus non-complicated course (n = 42). Results: Children aged < 1 year comprised majority (67%) of cohort and had lower complication rates (p = 0.062). Complicated course at surgery exclusively occurred in patients aged > 1 year (p = 0.003). Additionally, complicated group was older (p = 0.018), displayed leukocytosis (p < 0.001) and higher frequencies regarding presence of abdominal pain (p = 0.008) and abdominal mass (p = 0.034) on admission. Regression analysis identified present abdominal pain (OR (95% CI), 11.121 (1.152–107.337); p = 0.037) and leukocytosis (1.435 (1.070–1.925); p = 0.016) being associated with complicated course. Conclusions: This study provides evidence that symptomatic disease course follows an age-dependent complication pattern with lower complication rates at age < 1 year. Larger, studies have to clarify, if waiting for spontaneous urachal obliteration during the first year of life comprises a reasonable alternative to surgery.