Juvenile Pompe Disease: Retrospective Clinical Study

ntrodução: A doença de Pompe ou glicogenose tipo II é uma doença autossómica recessiva por deficiência de maltase ácida. É uma entidade rara, com prevalência de 1/40.000 nas populações holandesa e afro-americana e 1/46000 na população australiana. Embora se distingam três formas de apresentação (infantil, juvenil e do adulto), observa-se um amplo espectro clínico. Em Portugal está disponível terapêutica enzimática de substituição desde 2006.Material e Métodos: Fez-se o estudo retrospetivo de quatro doentes (duas das quais irmãs), baseado na revisão dos processos clínicos.Resultados: Em todas, a doença manifestou-se no segundo ano de vida. O tempo até ao diagnóstico variou entre dois e onze anos. Aquando do diagnóstico, todas apresentavam miopatia com atraso de aquisições motoras e em duas havia hipertrofia miocárdica. A suspeita clínica surgiu por insuficiência respiratória em contexto infeccioso em duas doentes. Em todas havia elevação da creatina quinase e das aminotransferases. Todas evoluíram com insuficiência respiratória crónica por síndrome restritiva. O diagnóstico foi baseado na diminuição da atividade da maltase ácida em fibroblastos (0 a 1,5% do limite inferior do normal). Na biópsia muscular, realizada em três doentes, demonstrou-se acumulação lisossómica de glicogénio. Todas apresentavam a mutação c.1064T > C no exão 6 do gene GAA (glucosidase-alpha-acid), em homozigotia numa delas, associada às mutações c.1666A > G no exão 12 e c.2065G > A no exão 15 nas duas irmãs e à mutação c.380G > T no exão 2 na doente mais nova. Todas iniciaram terapia enzimática de substituiçãologo que disponível, com boa tolerância. A doente mais jovem faleceu pouco depois. As outras mantêm medidas de suporteventilatório e fisioterapia, deslocando-se a mais velha, em cadeira de rodas, mantendo a irmã marcha independente e necessitando a mais nova de andarilho.Conclusão: Os nossos casos incluem-se clinicamente na forma juvenil da doença de Pompe. A hipótese de doença de Pompe deve ser considerada em lactentes com miocardiopatia e nas miopatias progressivas, especialmente as das cinturas e dos músculos respiratórios em qualquer idade. A elevação da creatina quinase é um dado sensível, embora inespecífico. Dada a grande variabilidade dos achados genéticos, a demonstração da redução da atividade da maltase ácida continua a ser o pilar do diagnóstico

Manganese determination by GFAAS in feces and fish feed slurries

This paper presents a simple, fast and sensitive method to determine manganese in samples of feces and fish feed by graphite furnace atomic absorption spectrometry (GFAAS) by the direct introduction of slurries into the graphite tube. The limits of detection (LOD) and quantification (LOQ) calculated for 20 readings of the blank of the standard slurries (0.50 % m/v of feces or feed devoid of manganese) were 28 and 92 μg kg-1 for the standard feces slurries and 34 and 110 μg kg-1 for the standard feed slurries. The proposed method was applied in bioavailability studies of manganese in different fish feeds and their results proved compatible with those obtained for samples mineralized by acid digestion using microwave oven. ©2007 Sociedade Brasileira de Química

Pristine carbon nanotubes for an efficient L-asparaginase immobilization

The enzyme L-asparaginase (ASNase) presents effective antineoplastic properties for acute lymphoblastic leukemia treatment, besides their potential use in the food sector to decrease acrylamide formation. Considering their applications, the improvement of these enzyme properties by efficient immobilization techniques is in high demand. Carbon nanotubes are promising enzyme immobilization supports since these materials have increased surface area and effective capacity for enzyme loading. Accordingly, in this study, multi-walled carbon nanotubes (MWCNTs) were explored as novel supports for ASNase immobilization by a simple adsorption method. The effect of pH, the contact time of immobilization, and the ASNase to nanoparticles mass ratio were optimized according to the enzyme immobilization yield and relative recovered activity. The enzyme-MWCNTs bioconjugation was confirmed by thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) studies. MWCNTs have a high ASNase loading capacity, with a maximum immobilization yield of 90%. The adsorbed ASNase retains 90% of the initial enzyme activity at the optimized conditions (pH 8, 60 min, and 1.5×10-3 g.mL-1 of ASNase). According to these results, ASNase immobilized onto MWCNTs can find in several areas improved applications, namely biosensors, medicine, and the food industry.publishe

Superior operational stability of immobilized L-asparaginase over surface-modified carbon nanotubes

L-asparaginase (ASNase, EC 3.5.1.1) is an enzyme that catalyzes the L-asparagine hydrolysis into L-aspartic acid and ammonia, being mainly applied in pharmaceutical and food industries. However, some disadvantages are associated with its free form, such as the ASNase short half-life, which may be overcome by enzyme immobilization. In this work, the immobilization of ASNase by adsorption over pristine and modified multi-walled carbon nanotubes (MWCNTs) was investigated, the latter corresponding to functionalized MWCNTs through a hydrothermal oxidation treatment. Different operating conditions, including pH, contact time and ASNase/MWCNT mass ratio, as well as the operational stability of the immobilized ASNase, were evaluated. For comparison purposes, data regarding the ASNase immobilization with pristine MWCNT was detailed. The characterization of the ASNase-MWCNT bioconjugate was addressed using different techniques, namely Transmission Electron Microscopy (TEM), Thermogravimetric Analysis (TGA) and Raman spectroscopy. Functionalized MWCNTs showed promising results, with an immobilization yield and a relative recovered activity of commercial ASNase above 95% under the optimized adsorption conditions (pH 8, 60 min of contact and 1.5 × 10-3 g mL-1 of ASNase). The ASNase-MWCNT bioconjugate also showed improved enzyme operational stability (6 consecutive reaction cycles without activity loss), paving the way for its use in industrial processes.publishe

Yicathins B and C and analogues: total synthesis, lipophilicity and biological activities

Natural products had always be an important source of new hits and leads in drug discovery. The marine environment has been regarded as a significant souce of novel and exquisite bioactive compounds. Yicathins B and C are two marine derived xanthones that have shown antibacterial and antifungal activities. Herein, the total synthesis of these yicathins is reported for the first time as well as six novel analogues. As marine natural products tend to bear very lipophilic scaffolds, the lipophilicity of yicathins and its analogues was evaluated using the classical octanol:water system and a biomimetic model based system. As the xanthonic nucleus is a â privileged structureâ , other biological activities were evaluated, namely antitumor and anti-inflammatory activities. An interesting anti-inflammatory activity was identified for yicathins analogues that paves the way for the design of dual activity (anti-infective and anti-inflammatory) marine inspired xanthones derivatives.This work was supported through national funds provided by FCT/MCTES - Foundation for Science and Technology from the Minister of Science, Technology and Higher Education (PIDDAC) and European Regional Development Fund (ERDF) through the COMPETE - Programa Operacional Factores de Competitividade (POFC) programme, under the projects PTDC/MAR-BIO/4694/2014 (reference POCI-01-0145-FEDER-016790; Project 3599 - Promover a ProducAo Cientifica e Desenvolvimento Tecnologico e a ConstituicAo de Redes Tematicas (3599-PPCDT)) and PTDC/SAU-PUB/28736/2017 (reference POCI-01-0145-FEDER- 028736) in the framework of the programme PT2020. D. R. P. L. is grateful for research grant PTDC/MAR-BIO/4694/2014-BI-2017-003. J. X. S. thanks the FCT PhD Programmes and Programa Operacional Capital Humano (POCH), specifically the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences), reference PD/00016/2012; through the FCT and POCH for PhD grants (SFRH/BD/98105/2013 and SFRH/BD/116167/2016). The authors would like to thank Sara Cravo and Gisela Adriano for the technical support, the Centro de Apoio Cientifico e Tecnoloxico a Investigation (C.A.C.T.I., University of Vigo, Pontevedra, Spain) for HRMS analysis, the Centro de Materiais da Universidade do Porto (CEMUP, Porto, Portugal) for HRMS, and the Departamento de Quimica da Universidade de Aveiro (Portuguese NMR network) for the NMR analysis

Determinação de fósforo biodisponível em rações de peixes utilizando extração assistida por ultra-som e espectrofotometria no visível

The aim of the present work was to develop and optimize a method for determination of bioavailable phosphorus in samples of feces and fish feed using ultrasound extraction and subsequent quantification by visible spectrophotometry. Using as extractor solution HNO3 0.50 mol L-1, the great conditions of extraction established were: sample mass - 100 mg, samples granulometry - < 60 µm, sonification time - five cycles of 40 s and ultrasound potency - 136 W. The proposed method was applied in studies of digestibility of this nutrient in different feeds used in diets of juvenile of Nile tilapia

Monitoring Adherence to Asthma Inhalers Using the InspirerMundi App: Analysis of Real-World, Medium-Term Feasibility Studies

Background: Poor medication adherence is a major challenge in asthma and objective assessment of inhaler adherence is needed. InspirerMundi app aims to monitor inhaler adherence while turning it into a positive experience through gamification and social support. Objective: We assessed the medium-term feasibility of the InspirerMundi app to monitor inhaler adherence in real-world patients with persistent asthma (treated with daily inhaled medication). In addition, we attempted to identify the characteristics of the patients related to higher app use. Methods: Two real-world multicenter observational studies, with one initial face-to-face visit and a 4-month telephone interview, were conducted in 29 secondary care centers from Portugal. During an initial face-to-face visit, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients took a photo of the medication (inhaler, blister, or others) using the image-based medication detection tool. Medication adherence was calculated as the number of doses taken as a percentage of the number scheduled. Interacting with the app ≥30 days was used as the cut-off for higher app use. Results: A total of 114 patients {median 20 [percentile 25 to percentile 75 (P25-P75) 16-36] years, 62% adults} were invited, 107 (94%) installed the app and 83 (73%) completed the 4-month interview. Patients interacted with the app for a median of 18 [3-45] days, translated on a median use rate of 15 [3-38]%. Median inhaler adherence assessed through the app was 34 [4-73]% when considering all scheduled inhalations for the study period. Inhaler adherence assessed was not significantly correlated with self-reported estimates. Median adherence for oral and other medication was 41 [6-83]% and 43 [3-73]%, respectively. Patients with higher app use were slightly older (p = 0.012), more frequently taking medication for other health conditions (p = 0.040), and more frequently prescribed long-acting muscarinic antagonists (LAMA, p = 0.024). After 4 months, Control of Allergic Rhinitis and Asthma Test (CARAT) scores improved (p < 0.001), but no differences between patients interacting with the app for 30 days or less were seen. Conclusions: The InspirerMundi app was feasible to monitor inhaler adherence in patients with persistent asthma. The persistent use of this mHealth technology varies widely. A better understanding of characteristics related to higher app use is still needed before effectiveness studies are undertaken.info:eu-repo/semantics/publishedVersio

Measuring Adherence to Inhaled Control Medication in Patients with Asthma: Comparison Among an Asthma App, Patient Self‐Report and Physician Assessment

Background: Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment. Methods: This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0-100). Results: A total of 193 patients (72% female; median [P25-P75] age 28 [19-41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0-71]%; 1 month: 18 [0-48]%) than patient self-report (80 [60-95]) and physician assessment (82 [51-94]) (p 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001). Conclusions: Adherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.info:eu-repo/semantics/publishedVersio

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson