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PubMed | University of Groningen, University of Cincinnati, Alberta Health Services, Baylor College of Medicine and 61 more.
Type: Journal Article | Journal: Nature genetics | Year: 2016

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology.


PubMed | Institute of Endocrinology, Lithuanian University of Health Sciences, Örebro University, Data Management and 2 more.
Type: | Journal: BMC public health | Year: 2015

Both sleep duration and screen time have been suggested to affect childrens diet, although in different directions and presumably through different pathways. The present cross-sectional study aimed to simultaneously investigate the associations between sleep duration, screen time and food consumption frequencies in children.The analysis was based on 10 453 children aged 6-9 years from five European countries that participated in the World Health Organization European Childhood Obesity Surveillance Initiative. Logistic multilevel models were used to assess associations of parent-reported screen time as well as sleep duration (exposure variables) with consumption frequencies of 16 food items (outcome variables). All models were adjusted for age, sex, outdoor play time, maximum educational level of parents and sleep duration or screen time, depending on the exposure under investigation.One additional hour of screen time was associated with increased consumption frequencies of soft drinks containing sugar (1.28 [1.19;1.39]; odds ratio and 99% confidence interval), diet/light soft drinks (1.21 [1.14;1.29]), flavoured milk (1.18 [1.08;1.28]), candy bars or chocolate (1.31 [1.22;1.40]), biscuits, cakes, doughnuts or pies (1.22 [1.14;1.30]), potato chips (crisps), corn chips, popcorn or peanuts (1.32 [1.20;1.45]), pizza, French fries (chips), hamburgers(1.30 [1.18;1.43]) and with a reduced consumption frequency of vegetables (excluding potatoes) (0.89 [0.83;0.95]) and fresh fruits (0.91 [0.86;0.97]). Conversely, one additional hour of sleep duration was found to be associated with increased consumption frequencies of fresh fruits (1.11 [1.04;1.18]) and vegetables (excluding potatoes) (1.14 [1.07;1.23]).The results suggest a potential relation between high screen time exposure and increased consumption frequencies of foods high in fat, free sugar or salt whereas long sleep duration may favourably be related to childrens food choices. Both screen time and sleep duration are modifiable behaviours that may be tackled in childhood obesity prevention efforts.


Carvalho C.L.,University of Évora | Carvalho C.L.,National Health Research Institute | Lopes de Carvalho I.,National Health Institute Doutor Ricardo Jorge | Ze-Ze L.,National Health Research Institute | And 2 more authors.
Comparative Immunology, Microbiology and Infectious Diseases | Year: 2014

In recent years, several emerging zoonotic vector-borne infections with potential impact on human health have been identified in Europe, including tularaemia, caused by Francisella tularensis. This remarkable pathogen, one of the most virulent microorganisms currently known, has been detected in increasingly new settings and in a wide range of wild species, including lagomorphs, rodents, carnivores, fish and invertebrate arthropods. Also, a renewed concern has arisen with regard to F. tularensis: its potential use by bioterrorists. Based on the information published concerning the latest outbreaks, the aim of this paper is to review the main features of the agent, its biology, immunology and epidemiology. Moreover, special focus will be given to zoonotic aspects of the disease, as tularaemia outbreaks in human populations have been frequently associated with disease in animals. © 2014 Elsevier Ltd.


Correia V.,National Health Institute Doutor Ricardo Jorge | Santos L.A.,National Health Institute Doutor Ricardo Jorge | Santos L.A.,University of Lisbon | Giria M.,University of Lisbon | And 3 more authors.
Journal of Medical Virology | Year: 2015

Neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are currently the only effective antiviral drugs available worldwide for the management of influenza. The potential development of resistance is continually threatening their use, rationalizing and highlighting the need for a close and sustained evaluation of virus susceptibility. This study aimed to analyze and characterize the phenotypic and genotypic NAIs susceptibility profiles of A(H1N1)pdm09 viruses circulating in Portugal from 2009 to 2010/2011. A total of 144 cases of A(H1N1)pdm09 virus infection from community and hospitalized patients were studied, including three suspected cases of clinical resistance to oseltamivir. Oseltamivir resistance was confirmed for two of the suspected cases. Neuraminidase (NA) H275Y resistant marker was found in viruses from both cases but for one it was only present in 26.2% of virus population, raising questions about the minimal percentage of resistant virus that should be considered relevant. Cross-decreased susceptibility to oseltamivir and zanamivir (2-4 IC50 fold-change) was detected on viruses from two potentially linked community patients from 2009. Both viruses harbored the NA I223V mutation. NA Y155H mutation was found in 18 statistical non-outlier viruses from 2009, having no impact on virus susceptibility. The mutations at NA N369K and V241I may have contributed to the significantly higher baseline IC50 value obtained to oseltamivir for 2010/2011 viruses, compared to viruses from the pandemic period. These results may contribute to a better understanding of the relationship between phenotype and genotype, which is currently challenging, and to the global assessment of A(H1N1)pdm09 virus susceptibility profile and baseline level to NAIs. © 2014 Wiley Periodicals, Inc.

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