Microarray in clinical practice – utility vs complexity. Mixed phenotype of duplication 15q11.2q13.1 and deletion 16p11.2

Introduction: There’s a consensus to perform chromosomal microarray technique as first-tier clinical diagnostic test for individuals with developmental disabilities. However, given the complexity of clinical presentations, often several diagnostic methods are held before conducting microarray. Method: We report the case of a 5 year-old boy referred to Medical Genetics due to short stature, developmental disabilities and facial dysmorphic features. He was born from eutocic delivery after an uneventful pregnancy. He had psychomotor milestones delayed like sitting at 9 months and walking at 24 months, holding an immature broad-based gait. There was history of learning difficulties from both parents, and the mother has also short stature. On examination it was noted some facial dysmorphic features like high forehead, conical canines and rarefaction of the distal portion of the eyebrows. Due to the history of an episode of transient ataxia, and suspicion of an inherited metabolic disorder, he had already performed various analytical and imaging screenings, all normal. Results: Chromosomal microarray analysis revealed two pathogenic Copy Number Variants (CNV’s): 16p11.2 deletion and 15q11.2q13.1 duplication. The 15q11q13 microduplication syndrome (OMIM # 608636) is a very rare clinical entity with about 30 reported cases with maternal origin, and it is characterized by neurobehavioral disorder, hypotonia, cognitive impairment, epilepsy and short stature. The 16p11.2 microdeletion syndrome (OMIM # 613444) is also a rare clinical entity, with high penetrance, associated with obesity and developmental disabilities. Discussion: Despite the unquestionable utility of microarray, the correlation of the CNV's with the phenotype is often difficult by the rarity of these new microdeletion/duplication clinical entities. In this case the interpretation has increased difficulty because of the simultaneous existence of two distinct clinical entities. Segregation studies, which in the first step include parental analysis, are essential for genetic counseling and determining the risk of recurrence but also for a more accurate correlation genotype-phenotype

Quantum Configuration and Phase Spaces: Finsler and Hamilton Geometries

In this paper, we review two approaches that can describe, in a geometrical way, the kinematics of particles that are affected by Planck-scale departures, named Finsler and Hamilton geometries. By relying on maps that connect the spaces of velocities and momenta, we discuss the properties of configuration and phase spaces induced by these two distinct geometries. In particular, we exemplify this approach by considering the so-called $q$-de Sitter-inspired modified dispersion relation as a laboratory for this study. We finalize with some points that we consider as positive and negative ones of each approach for the description of quantum configuration and phases spaces.Comment: 22 pages. Matches published version. Invited contribution for Physics. Special Issue "New Advances in Quantum Geometry

Effects of a 10 km race on physiological and immunological responses

Introduction: The number of 10 km running races has been increasing in Brazil and the number of finishers almost triplicated in the last decade. However, there is limited amount of data showing the relationship between this event and the immune system response. Aim: Investigate the effects of a 10 km running race on physiological and immunological response in healthy well trained male volunteers. Methods: Fourteen male participants (32,21 ± 10,24 years old, 78,80 ± 9,30 kg) took part in this study. Ratings of perceived exertion (RPE), visual analog scale (VAS), heart rate (HR) and blood samples were taken before, immediately and 24 hours after the race. Lactate, glucose, creatine kinase (CK) and C-reactive protein (CRP), as well as leukocyte number and subpopulation of T cell (CD4+ and CD8+) were analyzed. Results: Participants completed this race in 49,85 ± 7,04 min. There was a significant increase post-race compared to pre-race for HR (67 ± 9 to 159 ± 21 bpm), RPE (6 ± 0 to 15 ± 2) and lactate (3.6 to 6.6 mmol/dL). Glucose levels did not present any significant changes. CK level did not change immediately after the race, but was higher (131,21 ± 62,50 to 286,85 ± 234,35 U/L ) at the 24 h post-race time point. CRP was lower at 24 h (8,37 ± 2,23 to 4,50 ± 2,28 mg/dL). VAS values changed from 0 (before) to 5,64 ± 2,20 (immediately after) to 2,21 ± 2,86 (24 hours). The number of circulating leukocyte (5,83 ± 0,89 to 9,15 ± 1,77 103/µL), neutrophil (2,96 ± 0,49 to 4,34 ± 0,73 103/µL), lymphocyte (2,21 ± 0,57 to 3,92 ± 1,27 103/µL), monocyte (0,46 ± 0,10 to 0,64 ± 0,23 103/µL) and basophil (0,05 ± 0,02 to 0,09 ± 0,03 103/µL) increased significantly immediately after the race, returning to the basal level in 24 h. There was no difference in circulating eosinophils number. The absolute number of CD4+ (828,5 ± 215,8 to 1063,2 ± 235,3 cell/µL) and CD8+ (766,92 ± 347,79 to 1470,30 ± 782,90 cell/µL) also increased immediately after the race returning to basal in 24 h. Significant reduction of the CD4+/CD8+ lymphocyte subpopulation ratio (1,21 ± 0,45 to 0,85 ± 0,33 cell/µL) was observed post-race returning to basal level at 24 h post-race. Results are presented as mean ± SD. (p\u3c0,0001). Conclusion: These results suggest that a 10 km running race is an intense physical activity and induces physiological changes. In addition, intense running provokes a significantly, although transient, modulation of the immune system, specifically of leukocyte sub-population

Development and characterization of microsatellite markers for Piptadenia Gonoacantha (fabaceae)

Microsatellite primers were designed for Piptadenia gonoacantha (Fabaceae) and characterized to estimate genetic diversity parameters. The species is a native tree from the Atlantic Forest biome commonly used in forest restoration; it has medicinal potential and the wood is economically useful. Twenty-eight microsatellite loci were identified from an enriched genomic library. Fifteen loci resulted in successful amplifications and were characterized in a natural population of 94 individuals. Twelve loci were polymorphic, with allele numbers ranging from three to 15 per locus, and expected and observed heterozygosities ranging from 0.2142 to 0.8325 and 0.190 to 0.769, respectively. The developed markers will be used in further studies of population genetics of P. gonoacantha, aimed at conservation and management of the species in natural populations and in forest restoration projects32CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP140036/2011-3sem informaçãoBiota/FAPESP-11/50296-

Host-defense peptides AC12, DK16 and RC11 with immunomodulatory activity isolated from Hypsiboas raniceps skin secretion

Inflammation is a natural defense mechanism of the immune system; however, when unregulated, it can lead to chronic illness. Glucocorticoids are the most commonly used agents to effectively treat inflammatory conditions, including autoimmune diseases, however these substances can trigger a number of side effects. Thus, viable alternatives to the use of these drugs would be advantageous. In this study, we have analyzed the anti-inflammatory profile of three synthetic peptides first identified in skin secretion of the tree frog Hypsiboas raniceps. Structural characterization was performed using NMR spectroscopy and Mass Spectrometry, and the peptides were tested in vitro in RAW 264.7 cells and in vivo in Balb/c mice for their functional properties. The samples did not show a significant antimicrobial profile. NMR spectroscopy indicated that AC12 (ACFLTRLGTYVC) has a disulfide bond between C2 and C11 and a β-sheet-turn-β-sheet conformation in aqueous solution. This peptide showed no cytotoxic effect in mammalian cells and it was the most effective in reducing anti-inflammatory markers, such as NO, TNF-α and IL-12. Peptide DK16 (DKERPICSNTFRGRKC) demonstrated anti-inflammatory properties in vitro, while RC11 (RCFRRRGKLTC) significantly altered the cell viability in RAW 264.7 but was shown to be safe in Balb/c erythrocytes. Our results indicate that, of the three peptides studied, AC12 is the most efficient in reducing anti-inflammatory markers, and it could be a potential agent for the treatment of inflammatory diseases.publishe

Contribution of Efflux to the Emergence of Isoniazid and Multidrug Resistance in Mycobacterium tuberculosis

Multidrug resistant (MDR) tuberculosis is caused by Mycobacterium tuberculosis resistant to isoniazid and rifampicin, the two most effective drugs used in tuberculosis therapy. Here, we investigated the mechanism by which resistance towards isoniazid develops and how overexpression of efflux pumps favors accumulation of mutations in isoniazid targets, thus establishing a MDR phenotype. The study was based on the in vitro induction of an isoniazid resistant phenotype by prolonged serial exposure of M. tuberculosis strains to the critical concentration of isoniazid employed for determination of drug susceptibility testing in clinical isolates. Results show that susceptible and rifampicin monoresistant strains exposed to this concentration become resistant to isoniazid after three weeks; and that resistance observed for the majority of these strains could be reduced by means of efflux pumps inhibitors. RT-qPCR assessment of efflux pump genes expression showed overexpression of all tested genes. Enhanced real-time efflux of ethidium bromide, a common efflux pump substrate, was also observed, showing a clear relation between overexpression of the genes and increased efflux pump function. Further exposure to isoniazid resulted in the selection and stabilization of spontaneous mutations and deletions in the katG gene along with sustained increased efflux activity. Together, results demonstrate the relevance of efflux pumps as one of the factors of isoniazid resistance in M. tuberculosis. These results support the hypothesis that activity of efflux pumps allows the maintenance of an isoniazid resistant population in a sub-optimally treated patient from which isoniazid genetically resistant mutants emerge. Therefore, the use of inhibitors of efflux should be considered in the development of new therapeutic strategies for preventing the emergence of MDR-TB during treatment

Educational and economic determinants of food intake in Portuguese adults: a cross-sectional survey

BACKGROUND: Understanding the influences of educational and economic variables on food consumption may be useful to explain food behaviour and nutrition policymaking. The aim of this study was to evaluate the importance of educational and economic factors in determining food pattern in Portuguese adults. METHODS: A cross-sectional study in a representative sample of Portuguese adults (20977 women and 18663 men). Participants were distributed in four categories according to years of education (≤4, 5–9, 10–12, and >12) and income (≤314 euros, 315–547 euros, 548–815 euros, and >815 euros). Logistic regression models were fitted to estimate the magnitude of the association between food groups and education/income, adjusting for confounders. RESULTS: In both genders, the odds favouring milk, vegetable soup, vegetables, fruit, and fish consumption, increased significantly with education, for those having >12 years of education compared to those with ≤4 years; the odds favouring wine, and spirits consumption decreased significantly with education, for those having >12 years of education compared to those with ≤4 years. In males, the odds favouring starchy foods and meat consumption decreased significantly with income, while for milk, the odds increased with higher income (those having >815 euros compared to those with ≤314 euros). CONCLUSIONS: The low and high income groups are or tend to be similar in regard to several food groups consumption, and access to education/information appears to be the key element to a better food pattern as indicated by higher frequency of milk, vegetable soup, vegetables, fruit, and fish consumption

Produção de memórias falsas com listas de associados : análise do efeito do nível de processamento e da natureza da prova de memória

As memórias falsas têm sido amplamente estudadas com base num procedimento experimental designado paradigma DRM (Deese/Roediger/McDermott). Esse paradigma promove a criação de ilusões de memória a partir da apresentação de listas de palavras associadas a um item que não consta da lista. Uma das linhas de investigação com o paradigma DRM visa identificar o momento da criação das falsas memórias e explicar os mecanismos que estão na sua origem. Neste artigo, pretendemos fazer uma revisão da investigação sobre o efeito do nível de processamento e da natureza da tarefa de memória na facilitação ou inibição da produção de memórias falsas com listas de associados semânticos.False memories have been widely studied using an experimental procedure called DRM paradigm (Deese/Roediger/McDermott). This paradigm produces memory illusions due to the presentation of lists of words associated to a critical nonpresented word. One line of research on this topic aims at identifying the moment when the false memories are created and the explanation of the mechanisms underling false memories. In this paper we present a review about the effect of level-of-processing and the nature of memory task for the boost or inhibition of false memories created by means of lists of semantic associates.Le paradigme DRM (Deese/Roediger/McDermott) est un des plus connus et plus robustes parmi les études des faux mémoires dans le contexte du laboratoire. Ce paradigme permet la création d illusions de mémoire à partir des mots sémantiquement associés à un item qui n a pas été présenté. Au milieu des investigations basées sur le paradigme DRM il y a des études dont l objectif est d identifier e d´expliquer les mécanismes qui sont à l origine de la production des faux mémoires. Plus spécifiquement, on a pour but de faire une révision de la recherche sur l effet du niveau de codification et de la nature des tâches de mémoire sur la facilitation ou l´inhibition de la production de faux mémoires à partir des mots sémantiquement associés.Los falsos recuerdos han sido muy estudiados mediante la aplicación del paradigma DRM (Deese/Roediger/McDermott). El paradigma permite producir ilusiones de memoria tras la presentación de listas de palabras asociadas a una palabra que no se incluye en la lista. Una de las líneas de investigación que utilizan el paradigma DRM busca identificar el preciso momento de la creación de falsos recuerdos y explicar los mecanismos que originan ese efecto. El objetivo de este artículo es hacer una revisión de la investigación sobre el efecto de los niveles de procesamiento y la naturaleza de la tarea de memoria en la facilitación y inhibición de la producción de falsos recuerdos con listas de asociados semánticos.Fundação para a Ciência e a Tecnologia (FCT)Centro de Investigação em Psicologia da Universidade do Minho (CIPsi