Usability of a home-based test for the measurement of fecal calprotectin in asymptomatic IBD patients.

The aim of our work was to test the usability of fecal calprotectin (FC) home-based test in inflammatory bowel disease (IBD) patients. METHODS: IBD patients were prospectively recruited. They had to measure FC with a dedicated tool and smartphone application, 5 times at two weeks intervals over an 8 weeks period. They had to fill in a usability questionnaire at the first and the last FC measurement. A System Usability Scale (SUS: 0-100) and the Global Score of Usability (GSU: 0-85) were calculated. FC was also centrally measured by ELISA. RESULTS: Fifty-eight patients were recruited. Forty-two performed at least one FC measurement and 27 performed all the FC requested measurements. The median (IQR) SUS (0-100) at the first and last use were 85 (78-90) and 81 (70-88), respectively; the median (IQR) GSU (0-85) at the first and last use were 74 (69-80) and 77 (68-83), respectively. Adherence to the planned measurements and usability of the tool were higher in females and in less severe disease. The intra-class correlation coefficient between home-based and centrally measured FC was 0.88. CONCLUSION: The adherence to home-based measurement of FC was fair. Usability scores for the home-based test were high. There was a good correlation with the centrally measured FC by ELISA

Acciones para la promoción de la lactancia materna en la prematuridad tardía

Objetivo: Identificar na literatura científica ações para a promoção do aleitamento materno na prematuridade tardia. Método: Trata-se de uma Revisão Integrativa da Literatura que tem como questão norteadora: quais ações promovem o aleitamento materno na prematuridade tardia? A coleta de dados foi realizada no mês de setembro de 2017, na base de dados PubMed. O período utilizado para o refinamento da busca foi de janeiro de 2006 a julho de 2017. Após a leitura e refinamento, foram incluídos 16 artigos na amostra deste estudo. Resultados: Quanto aos temas, foram encontrados artigos que abordaram ações de promoção do aleitamento materno para realização tanto nas maternidades, quanto em domicilio, com predomínio na maternidade. Discussão: O aleitamento materno na prematuridade tardia é um evento desafiador e pode ser frustrante para a mãe do prematuro; requer ajuda capacitada dos profissionais de saúde e dos serviços de saúde nas maternidades e na atenção básica. Conclusão: O aleitamento materno na prematuridade tardia é uma estratégia que contribui para redução das taxas de morbimortalidade infantil.Objective: To identify in the scientific literature actions to promote breastfeeding in late prematurity. Method: This is an Integrative Review of Literature that has as guiding question: which actions promote breastfeeding in late prematurity? Data collection was performed in September 2017, in the PubMed database. The period used for the refinement of the search was from January 2006 to July 2017. After reading and refinement, 16 articles were included in the sample of this study. Results: In the themes, articles were found that addressed actions to promote breastfeeding for both maternity and home care, with predominance in the maternity. Discussion: The breastfeeding in late prematurity is a challenging event and can be frustrating for the mother of the premature; requires skilled assistance from health professionals and health services in maternity wards and primary care. Conclusions: Breastfeeding in late prematurity is a strategy that contributes to the reduction of infant morbidity and mortality rates.Objetivo: Identificar en la literatura científica acciones para la promoción de la lactancia materna en prematuridad tardía. Método: Se trata de una Revisión Integrativa de la Literatura que tiene como cuestión orientadora: qué acciones promueven la lactancia materna en la prematuridad tardía? La recolección de datos se realizó en el mes de septiembre de 2017, en la base de datos PubMed. El período utilizado para el refinamiento de la búsqueda fue de enero de 2006 a julio de 2017. Después de la lectura y el refinamiento, se incluyeron 16 artículos en la muestra de este estudio. Resultados: En cuanto a los temas, se encontraron artículos que abordaron acciones de promoción de la lactancia materna para realización tanto en las maternidades, como en domicilio, con predominio en la maternidad. Discusión: La lactancia materna en la prematuridad tardía es un acontecimiento desafiante y puede ser frustrante para la madre del prematuro; requiere ayuda capacitada de los profesionales de salud y de los servicios de salud en las maternidades y en la atención básica. Conclusión: La lactancia materna en la prematuridad tardía es una estrategia que contribuye a la reducción de las tasas de morbimortalidad infantil

Case Report Beneficial Effect of Conversion to Belatacept in Kidney-Transplant Patients with a Low Glomerular-Filtration Rate

Belatacept has been found to be efficient at preserving good kidney function in maintenance kidney-transplant patients. Herein, we report on the use of belatacept as a rescue therapy for two kidney-transplant patients presenting with severe adverse events after treatment with calcineurin inhibitors (CNIs) and mammalian target-of-rapamycin (mTOR) inhibitors. Two kidney-transplant patients developed severely impaired kidney function after receiving CNIs. The use of everolimus was associated with severe angioedema. Belatacept was then successfully used to improve kidney function in both cases, even though estimated glomerularfiltration rate before conversion was <20 mL/min. These case reports show that belatacept can be used as a rescue therapy, even if kidney function is very low in kidney-transplant patients who cannot tolerate CNIs and/or mTOR inhibitors

Progressive Structural Defects in Canine Centronuclear Myopathy Indicate a Role for HACD1 in Maintaining Skeletal Muscle Membrane Systems

Mutations in HACD1/PTPLA cause recessive congenital myopathies in humans and dogs. Hydroxyacyl-coA dehydratases are required for elongation of very long chain fatty acids, and HACD1 has a role in early myogenesis, but the functions of this striated muscle-specific enzyme in more differentiated skeletal muscle remain unknown. Canine HACD1 deficiency is histopathologically classified as a centronuclear myopathy (CNM). We investigated the hypothesis that muscle from HACD1-deficient dogs has membrane abnormalities in common with CNMs with different genetic causes. We found progressive changes in tubuloreticular and sarcolemmal membranes and mislocalized triads and mitochondria in skeletal muscle from animals deficient in HACD1. Furthermore, comparable membranous abnormalities in cultured HACD1-deficient myotubes provide additional evidence that these defects are a primary consequence of altered HACD1 expression. Our novel findings, including T-tubule dilatation and disorganization, associated with defects in this additional CNM-associated gene provide a definitive pathophysiologic link with these disorders, confirm that dogs deficient in HACD1 are relevant models, and strengthen the evidence for a unifying pathogenesis in CNMs via defective membrane trafficking and excitation-contraction coupling in muscle. These results build on previous work by determining further functional roles of HACD1 in muscle and provide new insight into the pathology and pathogenetic mechanisms of HACD1 CNM. Consequently, alterations in membrane properties associated with HACD1 mutations should be investigated in humans with related phenotypes

Past as global trade governance prelude: reconfiguring debate about reform of the multilateral trading system

This paper peers backwards into the history of the multilateral trading system and its development over the past half century as a means of considering what may lie beyond the horizon for the future of global trade governance. Its purpose is to underscore the necessity and urgency for root-and-branch reform of the multilateral trading system. It achieves this by comparing and contrasting the global trading system of 50 years ago with its modern-day equivalent and its likely future counterpart half-a-century hence. In so doing, the paper throws into sharp relief not only the inadequacies of global trade governance today but also the damaging consequences of not fundamentally reforming the system in the near future, with a particular emphasis on the past, present and future development of the world’s poorest and most marginalised countries

Modulation of RNA splicing enhances response to BCL2 inhibition in leukemia.

Therapy resistance is a major challenge in the treatment of cancer. Here, we performed CRISPR-Cas9 screens across a broad range of therapies used in acute myeloid leukemia to identify genomic determinants of drug response. Our screens uncover a selective dependency on RNA splicing factors whose loss preferentially enhances response to the BCL2 inhibitor venetoclax. Loss of the splicing factor RBM10 augments response to venetoclax in leukemia yet is completely dispensable for normal hematopoiesis. Combined RBM10 and BCL2 inhibition leads to mis-splicing and inactivation of the inhibitor of apoptosis XIAP and downregulation of BCL2A1, an anti-apoptotic protein implicated in venetoclax resistance. Inhibition of splicing kinase families CLKs (CDC-like kinases) and DYRKs (dual-specificity tyrosine-regulated kinases) leads to aberrant splicing of key splicing and apoptotic factors that synergize with venetoclax, and overcomes resistance to BCL2 inhibition. Our findings underscore the importance of splicing in modulating response to therapies and provide a strategy to improve venetoclax-based treatments