Biallelic PI4KA variants cause a novel neurodevelopmental syndrome with hypomyelinating leukodystrophy.

Phosphoinositides are lipids that play a critical role in processes such as cellular signalling, ion channel activity and membrane trafficking. When mutated, several genes that encode proteins that participate in the metabolism of these lipids give rise to neurological or developmental phenotypes. PI4KA is a phosphoinositide kinase that is highly expressed in the brain and is essential for life. Here we used whole exome or genome sequencing to identify 10 unrelated patients harbouring biallelic variants in PI4KA that caused a spectrum of conditions ranging from severe global neurodevelopmental delay with hypomyelination and developmental brain abnormalities to pure spastic paraplegia. Some patients presented immunological deficits or genito-urinary abnormalities. Functional analyses by western blotting and immunofluorescence showed decreased PI4KA levels in the patients' fibroblasts. Immunofluorescence and targeted lipidomics indicated that PI4KA activity was diminished in fibroblasts and peripheral blood mononuclear cells. In conclusion, we report a novel severe metabolic disorder caused by PI4KA malfunction, highlighting the importance of phosphoinositide signalling in human brain development and the myelin sheath.

Screening Strategies to Improve Early Diagnosis in Endometrial Cancer.

Endometrial cancer is the most common gynecological malignancy in high-income countries and the sixth most common cancer in women. Overall incidence has risen in the last few decades as a consequence of the increase in the prevalence of its risk factors, mainly obesity and the aging of the population, and although diagnoses have increased across all age groups, the incidence rates have doubled in women under the age of 40 years. The survival rates of endometrial cancer are highly dependent on its stage at diagnosis, bringing to the fore the importance of early diagnosis. The aim of a screening strategy in this type of tumor should be to detect the disease in the pre-invasive or early stage (before developing myometrial invasion), which would improve cure rates, reduce the morbidity associated with aggressive treatment and offer uterus-sparing management options for younger women. The ideal screening tool in this scenario would be a minimally invasive, inexpensive and easy-to-perform test or auto-test, which could be implemented in a routine gynecologic checkup of patients at-risk or in the general adult population. In this comprehensive review, we aim to define the populations at higher risk of developing endometrial cancer, to assess the performance of current diagnostic tools when used in a screening setting and to discuss the accuracy of new molecular screening strategies.

Developing modular training components to support home hospital digital solutions: Results of a Delphi panel.

BACKGROUND: Home hospitalization (HH) has demonstrated to be a cost-effective alternative with respect ti traditional hospitalization. Digital technologies, such as remote monitoring, have the potential to contribute to its expansion. Tailored educational content is a need to ensure patient safety during the whole admission. PURPOSE: The objective of this study was to systematically obtain consensus on patients with HH using training in the digital monitoring system. The goal of this work was to develop an adaptable modular and personalized training program for patients to support quality and safety care for HH. METHODS: The methodological approach for developing the proposed training content followed a modified Delphi technique with a multidisciplinary group of experts with significant knowledge of health informatics and HH protocols in Spain. The study comprised two rounds of training material description and gathering were completed. In Round 1, the experts received 58 predefined items obtained from the literature review and protocol selection. 20 items were rejected for different reasons and 25 new items were proposed. In Round 2, the experts selected the final items to build on the training content for every type of user and illness. RESULTS: A total of 21 experts completed rounds 1 and 2. The consensus was reached at the end of Round 2 with the inclusion of 53 items to build the training material. This included 17 treatment procedures, 4 diagnosis procedures, 22 additional support content, and 10 content features that describe how to build and deliver customized training content. CONCLUSIONS: Participants agreed on the type of content, its structure, and delivery methods to build modular training materials that support patients when they are hospitalized at home with the help of digital monitoring tools. This information can be used to create HH training programs that support new HH protocols and provide a standard for evaluating the quality of existing educational materials and programs.

[Celiac disease: causes, pathology, and nutritional assessment of gluten-free diet. A review]. / Enfermedad celiaca: causas, patología y valoración nutricional de la dieta sin gluten. Revision.

INTRODUCTION: Introduction: celiac patients suffer deficiencies before and during their maintenance of a gluten-free diet. This is due to malabsorption, associated with the disease, and to non-enriched, mostly processed foods high in saturated fats and deficient in the minerals typically present in wheat. Objectives: the main objective of this review was to determine the molecular basis of celiac disease and the nutritional deficiencies that gluten-free diet entails, as well as an assessment of gluten-free diet and its nutritional deficiencies once the intestinal microvilli have been restored. Material and methods: a bibliographic search was carried out through electronic databases. The content of the review focuses on the pathogenesis of celiac disease and the assessment of gluten-free diet when established for treatment. Results: the main deficiencies that occur in untreated celiac patients are (calcium, iron, fiber, folic acid, omega-3, vitamin B12, and vitamin D). It has been observed that the quality of life of celiac patients, after starting treatment, is reduced, and this leads to low adherence to gluten-free diet. In addition, these gluten-free diets without proper follow-up by a nutritionist entail other deficits such as: an increase in the risk of cardiovascular, metabolic, overweight and obesity diseases. Conclusion: gluten-free diet, as followed by celiac patients, usually entails certain deficiencies such as group-B vitamins, vitamin D, calcium, iron, folic acid, and fiber, which is mainly due to the poor nutritional quality of gluten-free products as compared to their equivalents with gluten, and a scarce monitoring by health professionals.

INTRODUCCIÓN: Introducción: los pacientes celiacos sufren deficiencias antes y durante el mantenimiento de la dieta sin gluten; esto se debe a la malabsorción asociada a la enfermedad y a los alimentos no enriquecidos, en su mayoría procesados, altos en grasas saturadas y deficientes en los minerales típicamente presentes en el trigo. Objetivos: el principal objetivo de la presente revisión bibliográfica es recopilar aquellos trabajos que centren su atención en determinar las bases moleculares de la enfermedad celiaca y que pudieran explicar las deficiencias nutricionales que conlleva dicha dieta, y efectuar una valoración de la dieta sin gluten y sus deficiencias nutricionales una vez restauradas las microvellosidades intestinales. Material y métodos: se ha realizado una búsqueda bibliográfica a través de bases de datos electrónicas. El contenido de la revisión se ha centrado en la patogénesis de la enfermedad celiaca y la valoración de la dieta sin gluten que se instaura como tratamiento. Resultados: numerosos estudios encuentran una deficiencia nutricional de micronutrientes en los pacientes celiacos sin tratar, principalmente en términos de calcio, hierro, fibra, ácido fólico, omega-3, vitamina B12 y vitamina D. Se ha observado que la calidad de vida de los pacientes celiacos, una vez iniciado el tratamiento, se ve reducida y que ello conlleva una baja adherencia a la dieta sin gluten. Además, estas dietas sin gluten, en el caso de que se sigan sin la supervisión de un especialista en nutrición, conllevan un aumento del riesgo de sufrir enfermedades cardiovasculares y metabólicas, sobrepeso y obesidad. Conclusión: la dieta sin gluten que siguen los pacientes celiacos suele conllevar ciertas deficiencias nutricionales como, por ejemplo, déficits de vitaminas del grupo B, vitamina D, calcio, hierro, ácido fólico y fibra, lo que se debe principalmente a la deficiente calidad nutricional de los productos sin gluten con respecto a sus equivalentes con gluten y a un bajo seguimiento por parte de los profesionales sanitarios.