Uso da canga como rocha ornamental.

Canga is a residual product resistant to mechanical weathering and practically inert chemical weather. The wide occurrence of this material in the region of Ouro Preto viability their use on behalf of the community and encourage studies about their physical and chemical properties. In this context, this pioneering research supporting the use of canga in the ornamental rock sector focus as dimension stone. The samples collected in geological site of Ouro Preto was characterized using x-ray diffraction, density and porosity determinations, Rockwell hardness test, Schmidt rebound hammer test and chemical analysis. The Schmidt rebound hammer tests were very efficient to detect internal imperfections, which was proven by the test of porosity. In addition, the fact of this test be non - destructive with easy realization makes their use viable, because there is no material lost. The performance of material compared with quartzite, usually used as dimension stone, was proved for this purpose. Its properties even suggest the application in other sectors such as ceramics and construction.A canga ? um produto residual resistente ? meteoriza??o mec?nica e praticamente inerte ao intemperismo qu?mico. A grande ocorr?ncia desse material na regi?o de Ouro Preto e a viabiliza??o do seu uso em prol da comunidade incentivam o seu estudo e desperta o interesse em conhecer suas propriedades f?sicas e qu?micas. Nesse contexto, surge essa pesquisa pioneira fundamentando a utiliza??o da Canga no setor de rochas ornamentais com enfoque na arte da Cantaria. As amostras coletadas no s?tio geol?gico da regi?o em estudo foram caracterizadas utilizando difratometria de raios-X, ensaios de massa espec?fica e porosidade, determina??o de dureza Rockwell e ensaios n?o destrutivos com o escler?metro Schmidt. Os testes com o escler?metro mostraram-se muito eficientes para detectar imperfei??es internas na pe?a, o que foi comprovado pelo teste de porosidade. Al?m disso, o fato desse teste ser n?o destrutivo e de f?cil realiza??o torna a sua utiliza??o vi?vel, n?o ocorrendo perda de material. O desempenho do material no decorrer do estudo encoraja o seu prosseguimento, visto que, mediante correla??o realizada com quartzito, usualmente utilizado como rocha ornamental, foi comprovada a configura??o da canga para esta finalidade. Suas propriedades ainda sugerem a aplica??o em outros setores como de cer?mica e constru??o civil

Research Recommendations for Improving Measurement of Treatment Effectiveness in Depression

Background: Despite the steadily escalating psychological and economic burden of depression, there is a lack of evidence for the effectiveness of available interventions on functioning areas beyond symptomatology. Therefore, the main objective of this study was to give an insight into the current measurement of treatment effectiveness in depression and to provide recommendations for its improvement. Materials and Methods: The study was based on a multi-informant approach, comparing data from a systematic literature review, an expert survey with representatives from clinical practice (130), and qualitative interviews with patients (11) experiencing depression. Results: Current literature places emphasis on symptomatic outcomes and neglects other domains of functioning, whereas clinicians and depressed patients highlight the importance of both. Interpersonal relationships, recreation and daily activities, communication, social participation, work difficulties were identified as being crucial for recovery. Personal factors, neglected by the literature, such as self-efficacy were introduced by experts and patients. Furthermore, clinicians and patients identified a number of differences regarding the areas improved by psychotherapeutic or pharmacological interventions that were not addressed by the pertinent literature. Conclusion: Creation of a new cross-nationally applicable measure of psychosocial functioning, broader remission criteria, report of domain-specific information, and a personalized approach in treatment decision-making are the first crucial steps needed for the improvement of the measurement of treatment effectiveness in depression. A better measurement will facilitate the clinical decision making and answer the escalating burden of depression

Guidelines for diagnosis and treatment of Hunter Syndrome for clinicians in Latin America

This review aims to provide clinicians in Latin America with the most current information on the clinical aspects, diagnosis, and management of Hunter syndrome, a serious and progressive disease for which specific treatment is available. Hunter syndrome is a genetic disorder where iduronate-2-sulfatase (I2S), an enzyme that degrades glycosaminoglycans, is absent or deficient. Clinical manifestations vary widely in severity and involve multiple organs and tissues. An attenuated and a severe phenotype are recognized depending on the degree of cognitive impairment. Early diagnosis is vital for disease management. Clinical signs common to children with Hunter syndrome include inguinal hernia, frequent ear and respiratory infections, facial dysmorphisms, macrocephaly, bone dysplasia, short stature, sleep apnea, and behavior problems. Diagnosis is based on screening urinary glycosaminoglycans and confirmation by measuring I2S activity and analyzing I2S gene mutations. Idursulfase (recombinant I2S) (Elaprase®, Shire) enzyme replacement therapy (ERT), designed to address the underlying enzyme deficiency, is approved treatment and improves walking capacity and respiratory function, and reduces spleen and liver size and urinary glycosaminoglycan levels. Additional measures, responding to the multi-organ manifestations, such as abdominal/inguinal hernia repair, carpal tunnel surgery, and cardiac valve replacement, should also be considered. Investigational treatment options such as intrathecal ERT are active areas of research, and bone marrow transplantation is in clinical practice. Communication among care providers, social workers, patients and families is essential to inform and guide their decisions, establish realistic expectations, and assess patients' responses.Hospital de Clinicas de Porto Alegre Serviço de Génetica MédicaUniversidade Federal do Rio Grande do Sul Departamento de GéneticaInstituto Nacional de Genética Médica PopulacionalAsociación Colombiana de Neurología InfantilInstituto Mexicano del Seguro SocialInstituto de Estudios AvanzadosHospital de NiñosLa Misericordia University HospitalUniversidade Federal de São Paulo (UNIFESP) Centro de Referência em Erros Inatos do MetabolismoUniversidade Federal de BahiaUniversidad de Chile Instituto de Nutrición y Tecnología de los AlimentosHospital Italiano Instituto de Genética MédicaHospital Pequeno Príncipe Departamento de NeuropediatraHospital Universitario AustralUNIFESP, Centro de Referência em Erros Inatos do MetabolismoSciEL

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Eduardo Pondal. Rumores de los pinos. Gravado á fotoaugaforte

Proyecto de investigación desarrollado por José Fuentes Esteve en torno al fotoaguafuerte sobre cobre

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery