Relationship Between Glucocerebrosidase Activity and Clinical Response to Enzyme Replacement Therapy in Patients With Gaucher Disease Type I

The quantification of enzyme activity in the patient treated with enzyme replacement therapy (ERT) has been suggested as a tool for dosage individualization, so we conducted a study to evaluate the relationship between glucocerebrosidase activity and clinical response in patients with Gaucher disease type I (GD1) to ERT. The study included patients diagnosed with GD1, who were being treated with ERT, and healthy individuals. Markers based on glucocerebrosidase activity measurement in patients’ leucocytes were studied: enzyme activity at 15 min. post-infusion (Act75) reflects the amount of enzyme that is distributed in the body post-ERT infusion, and accumulated glucocerebrosidase activity during ERT infusion (Act75-0) indicates the total drug exposure during infusion. The clinical response was evaluated based on criteria established by Pastores et al. and Gaucher Severity Score Index. Statistical analysis included ROC analysis and area under the curve test. Act75 and Act75-0 were found to be moderate predictive markers of an optimal clinical response (area under the ROC of Act75 was 0.733 and Act75-0 was 0.817). Act75-0 showed statistical significance in its discriminative capacity (p < 0.05) for obtaining an optimal response to ERT. The cut-off point was 58% (RR = 1.800; 95% CI: 1.003–3.229; p < 0.05). Moreover, Act75 showed a significant and inverse correlation with the Gaucher Severity Score Index, and Act75 and Act75-0 presented a significant correlation with residual enzyme activity at diagnosis. Markers based on glucocerebrosidase activity have a good correlation with clinical response to ERT. Therefore, it could provide supporting clinical data for dose management in GD1 patients

Synthesis, microstructure and volumetry of novel metal thiocyanate ionic liquids with [BMIM] cation

We present a new family of ionic liquids (ILs) with a common cation, 1-butyl-3-methyl imidazolium, the popular [BMIM]+ (also written C4C1Im+) and a variety of anionic complexes (also called adducts) based in thiocyanate (SCN)?: one blank compound, BMIM(SCN), and ten doped with metals having different oxidation states: Al+3, Mn+2, Fe+3, Cr+3, Ni+2, Hg+2, Zn+2, Co+2, Cd+2 and Cu+, forming, respectively, [BMIM]3[Al(SCN)6], [BMIM]4 Mn(SCN)6, [BMIM]3 Fe(SCN)6, [BMIM]3 Cr(SCN)6, [BMIM]4 Ni(SCN)6, [BMIM]2 Hg(SCN)4, [BMIM]2 Zn(SCN)4, [BMIM]2 Co(SCN)4, [BMIM]2 Cd(SCN)4 and [BMIM]3 Cu(SCN)4. All of them were synthesized by us, except the blank IL and the Co thiocyanate, which are commercial. Obtained products have been characterized by NMR, and also by electrospray ionization, MS-ES, which allows the determination of the new ILs purities. Then, compounds have been analyzed using FT-IR and Raman spectroscopy. In addition, magnetic susceptibility and refractive index measurements were performed in some of the compounds studied, as well as thermal characterization using DSC and TGA. Finally, experimental measurements of density on all those ILs have been performed, and for some of the samples in a broad temperature range (about 100 K). In spite of being very similar compounds from the chemical point of view, they present quite different physical properties, including optical, thermal and magnetic ones? Also, they show different oxidation states (one with +1, six with +2 and other three with +3). We guess that this family of ILs will have interesting applications, mainly for photonic devices

O YouTube: potencialidades pedagógicas na aprendizagem da Língua Inglesa no 1.º ciclo do ensino básico

Mestrado em Ensino Precoce do InglêsO presente projeto de investigação procurou apresentar o YouTube como um banco de recursos audiovisuais, promotor do desenvolvimento das macrocapacidades de audição e de expressão oral, no processo de ensino/aprendizagem da Língua Inglesa no 1.º ciclo do ensino básico. Desta forma, procurámos tecer algumas considerações relativamente à origem e natureza orgânica do YouTube, que nos conduziram à visualização e à exploração de vídeos publicados no website, que promovessem, simultaneamente, o usufruto de imagem e som e, por conseguinte, o cumprimento de objetivos pedagógicos inerentes à aprendizagem significativa da língua estrangeira. O trabalho de pesquisa centrou-se num estudo de caso, cujo desenvolvimento providenciou a aplicação de vídeos e a realização de atividades diversas, numa turma de alunos do 4.º ano de escolaridade, tendo como base princípios decorrentes de métodos e abordagens utilizados no ensino de Inglês a crianças, auscultando-se o seu grau de envolvimento e participação no processo de aprendizagem. Do mesmo modo, e porque consideramos fundamental a troca de ideias e a partilha de experiências e práticas, especialmente no que se refere ao campo de ação da Educação, procurou-se estabelecer práticas de trabalho colaborativo e colegialidade entre as professoras envolvidas no decurso da investigação realizada.This research work aimed at describing the YouTube as a source of audiovisual materials, favourable to the development of listening and speaking skills concerning the process of English language teaching and learning in primary schools. Bearing in mind YouTube’s origins and organic nature, we engaged in selecting and exploring videos uploaded on the website, which conveyed both image and sound, in order to attain a set of pedagogical objectives aimed at a meaningful learning of the foreign language. The research work redefined itself as a case study, whose development consisted in using a number of videos and activities with fourth graders, having in mind principles from preferred methods and approaches in the teaching of English to Young Learners, as well as the assessment of their degree of involvement and participation in the learning process. Furthermore, and because we consider the sharing of ideas, experiences and practices of major importance, especially as far as Education is concerned, we tried to develop and enhance collaborative and collegial work between the teachers engaged in the course of the research work

Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation

BACKGROUND: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. METHODS: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. RESULTS: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. CONCLUSIONS: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients

Vitamin E prevents lipid peroxidation and iron accumulation in PLA2G6-Associated Neurodegeneration

23 Páginas.-- 17 FigurasPLA2G6-Associated Neurodegeneration (PLAN) is a rare neurodegenerative disease with autosomal recessive inheritance, which belongs to the NBIA (Neurodegeneration with Brain Iron Accumulation) group. Although the pathogenesis of the disease remains largely unclear, lipid peroxidation seems to play a central role in the pathogenesis. Currently, there is no cure for the disease.This work was supported by FIS PI16/00786 and PI19/00377 grants, Instituto de Salud Carlos III, Spain and Fondo Europeo de Desarrollo Regional (FEDR-Unión Europea), Proyectos de Investigación de Excelencia de la Junta de Andalucía CTS-5725 and PY18-850 and by AIDNAI (Association Internationale de Dystrophie Neuro Axonale Infantile), ENACH (Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro), AEPMI (Asociación de Enfermos de Patología Mitocondrial), FEDER (Federación Española de Enfermedades Raras) and Fundación MERK Salud. S. Povea-Cabello is a recipient of Ayudas para la Formación del Profesorado Universitario (FPU) from Ministerio de Universidades de España.Peer reviewe

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVE: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare

Variation in antiosteoporotic drug prescribing and spending across Spain. A population-based ecological cross-sectional study

Introduction: Evidence has shown that utilization of antiosteoporotic medications does not correspond with risk, and studies on other therapies have shown that adequacy of pharmaceutical prescribing might vary between regions. Nevertheless, very few studies have addressed the variability in osteoporotic drug consumption. We aimed to describe variations in pharmaceutical utilization and spending on osteoporotic drugs between Health Areas (HA) in Spain. Methods: Population-based cross-sectional ecological study of expenditure and utilization of the five therapeutic groups marketed for osteoporosis treatment in Spain in 2009. Small area variation analysis (SAVA) methods were used. The units of analysis were the 168 HA of 13 Spanish regions, including 7.2 million women aged 50 years and older. The main outcomes were the defined daily dose (DDD) per 1000 inhabitants and day (DDD/1000/Day) dispensed according to the pharmaceutical claims reimbursed, and the expenditure on antiosteoporotics at retail price per woman =50 years old and per year. Results: The average osteoporosis drug consumption was 116.8 DDD/1000W/Day, ranging from 78.5 to 158.7 DDD/1000W/Day between the HAs in the 5th and 95th percentiles. Seventy-five percent of the antiosteoporotics consumed was bisphosphonates, followed by raloxifene, strontium ranelate, calcitonins, and parathyroid hormones including teriparatide. Regarding variability by therapeutic groups, biphosphonates showed the lowest variation, while calcitonins and parathyroid hormones showed the highest variation. The annual expenditure on antiosteoporotics was €426.5 million, translating into an expenditure of €59.2 for each woman =50 years old and varying between €38.1 and €83.3 between HAs in the 5th and 95th percentiles. Biphosphonates, despite accounting for 79% of utilization, only represented 63% of total expenditure, while parathyroid hormones with only 1.6% of utilization accounted for 15% of the pharmaceutical spending. Conclusion: This study highlights a marked geographical variation in the prescription of antiosteoporotics, being more pronounced in the case of costly drugs such as parathyroid hormones. The differences in rates of prescribing explained almost all of the variance in drug spending, suggesting that the difference in prescription volume between territories, and not the price of the drugs, is the main source of variation in this setting. Data on geographical variation of prescription can help guide policy proposals for targeting areas with inadequate antiosteoporotic drug use

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Empirical investigation to explore potential gains from the amalgamation of Phase Changing Materials (PCMs) and wood shavings

The reduction of gained heat, heat peak shifting and the mitigation of air temperature fluctuations are some desirable properties that are sought after in any thermal insulation system. It cannot be overstated that these factors, in addition to others, govern the performance of such systems thus their effect on indoor ambient conditions. The effect of such systems extends also to Heating, Ventilation and Air-conditioning (HVAC) systems that are set up to operate optimally in certain conditions. Where literature shows that PCMs and natural materials such as wood-shavings can provide efficient passive insulation for buildings, it is evident that such approaches utilise methods that are of a degree of intricacy which requires specialist knowledge and complex techniques, such as micro-encapsulation for instance. With technical and economic aspects in mind, an amalgam of PCM and wood-shavings has been created for the purpose of being utilised as a feasible thermal insulation. The amalgamation was performed in the simplest of methods, through submerging the wood shavings in PCM. An experimental procedure was devised to test the thermal performance of the amalgam and compare this to the performance of the same un-amalgamated materials. Comparative analysis revealed that no significant thermal gains would be expected from such amalgamation. However, significant reduction in the total weight of the insulation system would be achieved that, in this case, shown to be up to 20.94%. Thus, further reducing possible strains on structural elements due to the application of insulation on buildings. This can be especially beneficial in vernacular architectural approaches where considerably large amounts and thicknesses of insulations are used. In addition, cost reduction could be attained as wood shavings are significantly cheaper compared to the cost of PCMs

Training future generations to deliver evidence-based conservation and ecosystem management

1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis. 2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice. 3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses. 4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.Peer reviewe