Summer Vacations not Only a Memory for Life, but Also a Rare Infection

Introduction: Rhinoscleroma is a rare, chronic, granulomatous disease that most frequently affects the upper respiratory tract, especially the nasal cavity and sometimes extends through the lower respiratory tract. Is associated with Klebsiella rhinoscleromatis, which is endemic in certain geographic regions namely Central America. The pathogenesis and risk factors remain unclear. Clinical case: We report a five years Old Portuguese boy, previously healthy, brought to the Emergency Department with epistaxis, without other accompanying signs or symptoms. The Otorhinolaryngologist (ORL) performed rhinoscopy and identified an intranasal bleeding mass. The MRI revealed an intranasal mass with extension to the ethmoid bone sinus, and performed biopsy. The histopathology was vital, making the diagnosis of Rhinoscleroma. The child had traveled abroad for the first time on vacations a year before to Dominican Republic. The bacteriologic exam identified a Klebsiella spp. sensible to the association of amoxicillin and clavulanic acid. Blood test performed excluded association of immunodeficiency. Since it’s a rare disease genetic study are under course. Monthly evaluation by ORL and pediatrician was performed which documented progressive reduction until total disappearing of the macro and microscopic lesion, and negative bacteriologic exam. Six months of antibiotic therapy were completed without any known secondary effects. The child remained asymptomatic up to the last visit, 3 months following treatment and has shown no evidence of recurrence. Conclusion: Globalization and free transit of people to areas far from origin countries here some rare diseases are endemic brings a new challenge to modern medicine. Sometimes vacations bring more than memories

Rhinoscleroma in a 5-year-old Portuguese Child

Rhinoscleroma is a chronic granulomatous infectious disease that is rare in Western Europe. We report the case of a 5-year-old Portuguese boy diagnosed with rhinoscleroma in the context of recurrent epistaxis. He had a 6-month course of antibiotic (amoxicillin plus clavulanate) therapy with full recovery

Heuristics for simulated annealing search of active sub-networks in bio-molecular interaction networks

Different kinds of ‘omics’ data for several organisms and bio-molecular interaction networks (e.g. reconstructed networks of biochemical reactions and protein-protein physical interactions) are becoming very common nowadays. These bio-molecular networks are being used as a platform to integrate genome-scale ‘omics’ datasets. Identification of sub-networks in these large networks that show maximum collective response to a perturbation is one the interesting problems to solve by using an integrative analysis. Sub-networks can be hypothesized to represent significant collective biological activity due to the underlying interactions between the bio-molecules. The biological activity can be estimated in several ways- for example coordinated change in the expression level (e.g. mRNA). Identifying these regions reduce complexity of the network to be analyzed in greater detail by revealing the regions that are perturbed by a conditionremoving the interactions that are potentially false-positive and not related to the response under study. As the simulated annealing does not guarantee to find the global optimum and may lead to an incomplete picture of the biological phenomenon, we report a method to estimate the theoretical optimal score curve. The simulated annealing algorithm (SA) used in this study is a slightly modified version of the algorithm by Ideker et al.. Each node in the graph is associated with a binary variable turning the node visible or invisible and therefore inducing several sub-graphs. In the standard formulation, the initial solution is obtained by randomly attributing 0 or 1 to the nodes of the graph. Based in concepts described above, we propose an alternative initialization method to improve the performance of the simulated annealing algorithm.Systems Biology as a Driver for Industrial Biotechnology (SYSINBIO

Application of the stretched simulated annealing method in the stability analysis of multicomponent systems using excess gibbs energy models

In this work, the Stretched Simulated Annealing Method was applied to identify the stationary points of the tangent plane distance function defined for the Gibbs energy. The classic excess Gibbs energy Non Random Two Liquid model was used for these studies in several multicomponent mixtures, for which specific numerical difficulties were shown. The results obtained by applying the methodology developed in this work were very satisfactory

Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis

Osteoporosis is associated with chronic iron overload secondary to hereditary hemochromatosis (HH), but the causative mechanisms are incompletely understood. The main objective of this study was to investigate the role of dietary iron on osteoporosis, using as biological model the Hfe-KO mice, which have a systemic iron overload. We showed that these mice show an increased susceptibility for developing a bone loss phenotype compared to WT mice, which can be exacerbated by an iron rich diet. The dietary iron overload caused an increase in inflammation and iron incorporation within the trabecular bone in both WT and Hfe-KO mice. However, the osteoporotic phenotype was only evident in Hfe-KO mice fed the iron-enriched diet. This appeared to result from an imbalance between bone formation and bone resorption driven by iron toxicity associated to Hfe-KO and confirmed by a decrease in bone microarchitecture parameters (identified by micro-CT) and osteoblast number. These findings were supported by the observed downregulation of bone metabolism markers and upregulation of ferritin heavy polypeptide 1 (Fth1) and transferrin receptor-1 (Tfrc), which are associated with iron toxicity and bone loss phenotype. In WT mice the iron rich diet was not enough to promote a bone loss phenotype, essentially due to the concomitant depression of bone resorption observed in those animals. In conclusion the dietary challenge influences the development of osteoporosis in the HH mice model thus suggesting that the iron content in the diet may influence the osteoporotic phenotype in systemic iron overload conditions.National Funds through Foundation for Science and Technology (FCT) Norte-01-0145-FEDER-000012 Portuguese Foundation for Science and Technology (FCT) SFRH/BD/77056/2011 European Regional Development Fund (FEDER) Norte-01-0145-FEDER-000012info:eu-repo/semantics/publishedVersio

Imunodeficiência Combinada Grave – O Diagnóstico Precoce é Importante?

Introdução: Os doentes com Imunodeficiência Combinada Grave (SCID) não diagnosticados evoluem inexoravelmente para a morte no primeiro ano de vida. Um elevado índice de suspeição é fundamental para o diagnóstico precoce, o factor mais importante para a sobrevida destas crianças. Objectivo: Apresentam-se três casos clínicos ilustrativos da importância da precocidade diagnóstica no prognóstico final. Casos clínicos: Caso clínico 1: Lactente do sexo masculino, com antecedentes de infecções respiratórias de repetição, internado aos sete meses na UCIP do HDE por pneumonia a Adenovírus com insuficiência respiratória. Necessitou de ventilação mecânica e de duas transfusões de concentrado eritrocitário na primeira semana de internamento. Teve exantema exuberante, interpretado como toxidermia. Evoluiu para doença pulmonar sequelar grave. Aos nove meses foi feito o diagnóstico de SCID hipomorfa com doença do enxerto contra o hospedeiro pós-transfusional, controlada com imunossupressão (ciclosporina e glucocorticoides). Não foi transplantado com células progenitoras hematopoiéticas por não reunir condições clínicas. Na sequência de uma intercorrência respiratória veio a falecer aos 14 meses. Caso clínico 2: Lactente do sexo masculino, internado aos 6 meses no HDE por pneumonia intersticial hipoxemiante. Isolado P. jiroveci no lavado bronco-alveolar e feito o diagnóstico presuntivo de BCGite disseminado em criança com SCID T-B+NK-. Após estabilização clínica e esplenectomia foi transplantado com células progenitoras hematopoiéticas de dador fenoidêntico não aparentado. Dada a BCGite disseminada necessitou de vários ciclos de infusão de células do dador para uma reconstituição imunitária lenta e progressiva. Seis meses pós-transplante está clinicamente bem, com quimerismo linfóide T e NK completo. Caso clínico 3: Lactente do sexo masculino, internado aos 17 dias de vida por infecção respiratória alta e bacteriémia a M. catarrhalis. Reinternado quinze dias depois por sépsis a MRSA e linfopénia. A avaliação efectuada permitiu o diagnóstico de SCID T-B+NK- por defeito na cadeia gamma comum. Transplantado com células progenitoras hematopoiéticas de dador genoidêntico aos 4 meses, sem condicionamento. Clinicamente bem, seis meses pós-transplante, com reconstituição imunitária satisfatória. Conclusão: Esta doença tem uma prevalência não negligenciável e apenas com elevado indice de suspeição se pode estabelecer um plano de tratamento eficaz

Responsive bystander behaviour in cyberbullying: a path through self-efficacy

Bystander behaviour and self-efficacy beliefs play an important role in cyberbullying incidence. This study tested the relationship between the Bystander Intervention Model phases and the mediating role of adolescents’ self-efficacy beliefs. Children from the fifth to twelfth grade (N = 676) participated in this study by responding to questionnaires concerning the various phases of the Bystander Intervention Model and self-efficacy beliefs to resolve cyberbullying-related problems. Through structural equation modelling, noticing an incident of cyberbullying had a direct and indirect effect on aggressive behaviour, and an indirect effect on reporting and problem-solving behaviour. The indirect effect of interpreting the event through attributing responsibility was significant for aggressive and problem-solving behaviour. The mediator role of reflective decision-making had a stronger effect on direct problem-solving. Self-efficacy beliefs significantly affected the relationship between interpreting the event and all behaviour, but stronger for direct problem-solving. These findings help explain empirically how bystanders respond to incidents of cyberbullying.info:eu-repo/semantics/acceptedVersio

OptFlux3: an improved platform for in silico design of cellular factories

The rational design of cellular factories for industrial biotechnology aims to create optimized organisms for the production of bulk chemicals, pharmaceuticals, food ingredients and enzymes, among others. Metabolic engineering (ME) plays a key role in this process, supported by the latest advances in genetic engineering in combination with computational tools to define targets for strain improvement. OptFlux is an open-source reference computational platform for the optimization of cellular factories by the application of in silico ME methods, designed for non-computational experts by providing a user-friendly interface. It allows to load genome-scale models from several sources to be used in the prediction of cellular behavior and identification of metabolic targets for genetic engineering. Its latest version, OptFlux3, allows to perform the simulation of wild type and mutant strains (allowing the simulation of gene/ reaction deletion and over/under expression). Regarding strain optimization, the new architecture opts for a multi-objective framework, allowing users to easily add different goals as optimization targets in a flexible way. Specialized multi-objective algorithms, co-exist with traditional single objectives algorithms to be applied for each case. Also, OptFlux3 includes a new visualization framework for metabolic models and phenotype simulations and a new plug-in management interface that allows to install and remove plug-ins in execution time. Currently available plug-ins include the calculation and visualization of elementary modes, topological analysis and the ability to add reactions/ pathways to existing models. OptFlux is made freely available for all major operating systems, together with suitable documentation in www.optflux.org