The Natural Course of Bosch-Boonstra-Schaaf Optic Atrophy Syndrome.

(Likely) pathogenic variants in NR2F1 are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS, OMIM #615722), a rare neurodevelopmental disorder. Patients present with a variety of symptoms, including intellectual disability, developmental delay, visual impairment, muscular hypotonia, seizures, and/or autistic features. Since it was first described in 2014, the phenotype has steadily expanded.

Hao-Fountain syndrome: 32 novel patients reveal new insights into the clinical spectrum.

Hao-Fountain syndrome (HAFOUS, OMIM: #616863) is a neurodevelopmental disorder caused by pathogenic variants in the gene USP7 coding for USP7, a protein involved in several crucial cellular homeostatic mechanisms and the recently described MUST complex. The phenotype of HAFOUS is insufficiently understood, yet there is a great need to better understand the spectrum of disease, genotype-phenotype correlations, and disease trajectories. We now present a larger cohort of 32 additional individuals and provide further clinical information about six previously reported individuals.

DNA methylation episignature, extension of the clinical features, and comparative epigenomic profiling of Hao-Fountain syndrome caused by variants in USP7.

Purpose: Hao-Fountain syndrome (HAFOUS) is a neurodevelopmental disorder caused by pathogenic variants in USP7. HAFOUS is characterized by developmental delay, intellectual disability, speech delay, behavioral abnormalities, autism spectrum disorder, seizures, hypogonadism, and mild dysmorphic features. We investigated the phenotype of 18 participants with HAFOUS and performed DNA methylation (DNAm) analysis, aiming to generate a diagnostic biomarker.

-associated Chung-Jansen syndrome: Report of 23 new individuals.

In 2016 and 2018, Chung, Jansen and others described a new syndrome caused by haploinsufficiency of (pleckstrin homology domain interacting protein, OMIM *612,870) and mainly characterized by developmental delay (DD), learning difficulties/intellectual disability (ID), behavioral abnormalities, facial dysmorphism and obesity (CHUJANS, OMIM #617991). So far, alterations appear to be a rare cause of DD/ID. "Omics" technologies such as exome sequencing or array analyses have led to the identification of distinct types of alterations of , including, truncating variants, missense substitutions, splice variants and large deletions encompassing portions of the gene or the entire gene as well as adjacent genomic regions.

Deletion of mTOR in liver epithelial cells enhances hepatic metastasis of colon cancer.

Activation of the mechanistic target of rapamycin (mTOR) pathway is frequently found in cancer, but mTOR inhibitors have thus far failed to demonstrate significant antiproliferative efficacy in the majority of cancer types. Besides cancer cell-intrinsic resistance mechanisms, it is conceivable that mTOR inhibitors impact on non-malignant host cells in a manner that ultimately supports resistance of cancer cells. Against this background, we sought to analyze the functional consequences of mTOR inhibition in hepatocytes for the growth of metastatic colon cancer.

A retrospective analysis of growth hormone therapy in children with Schaaf-Yang syndrome.

Short stature is a common phenotype in children with Schaaf-Yang syndrome (SYS). Prader-Willi syndrome (PWS) and SYS share several phenotypic features including short stature, muscular hypotonia and developmental delay/intellectual disability. Evidence exists that similar to PWS, growth hormone (GH) deficiency may also be a feature of SYS.

Cardiac MRI in Patients with Acute Chest Pain.

Acute chest pain is a common reason for visits to the emergency department. It is important to distinguish among the various causes of acute chest pain, because treatment and prognosis are substantially different among the various conditions. It is critical to exclude acute coronary syndrome (ACS), which is a major cause of hospitalization, death, and health care costs worldwide.

Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT versus IRT/PAP/IRT.

Identifying newborns at risk for cystic fibrosis (CF) by newborn screening (NBS) using dried blood spot (DBS) specimens provides an opportunity for presymptomatic detection. All NBS strategies for CF begin with measuring immunoreactive trypsinogen (IRT). Pancreatitis-associated protein (PAP) has been suggested as second-tier testing.

Spanish Clinical Guidelines on Vascular Access for Haemodialysis.

Vascular access for haemodialysis is key in renal patients both due to its associated morbidity and mortality and due to its impact on quality of life. The process, from the creation and maintenance of vascular access to the treatment of its complications, represents a challenge when it comes to decision-making, due to the complexity of the existing disease and the diversity of the specialities involved. With a view to finding a common approach, the Spanish Multidisciplinary Group on Vascular Access (GEMAV), which includes experts from the five scientific societies involved (nephrology [S.

Enhanced cardiac Akt/protein kinase B signaling contributes to pathological cardiac hypertrophy in part by impairing mitochondrial function via transcriptional repression of mitochondrion-targeted nuclear genes.

Sustained Akt activation induces cardiac hypertrophy (LVH), which may lead to heart failure. This study tested the hypothesis that Akt activation contributes to mitochondrial dysfunction in pathological LVH. Akt activation induced LVH and progressive repression of mitochondrial fatty acid oxidation (FAO) pathways.

Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma.

Molecular signatures have identified several subsets of diffuse large B cell lymphoma (DLBCL) and rational targets within the B cell receptor (BCR) signaling axis. The OxPhos-DLBCL subset, which harbors the signature of genes involved in mitochondrial metabolism, is insensitive to inhibition of BCR survival signaling but is functionally undefined. We show that, compared with BCR-DLBCLs, OxPhos-DLBCLs display enhanced mitochondrial energy transduction, greater incorporation of nutrient-derived carbons into the tricarboxylic acid cycle, and increased glutathione levels.

Formation of S-(carboxymethyl)-cysteine in rat liver mitochondrial proteins: effects of caloric and methionine restriction.

Maillard reaction contributes to the chemical modification and cross-linking of proteins. This process plays a significant role in the aging process and determination of animal longevity. Oxidative conditions promote the Maillard reaction.

Paediatric patients with a tracheostomy: a multicentre epidemiological study.

Changes in the indications for tracheostomy in children have led to the progressively greater involvement of the paediatric pulmonologist in the care of these patients. The aim of this study was to review the current profile of tracheostomised children in Spain. We undertook a longitudinal, multicentre study over 2 yrs (2008 and 2009) of all patients aged between 1 day and 18 yrs who had a tracheostomy.

Diffusion-weighted imaging of the chest.

Diffusion-weighted imaging (DWI) is feasible in the chest with currently available MR imaging scanners, although it is technically demanding. Although there is scarce clinical experience, the use of DWI has shown promising results in the characterization of pulmonary nodules, in lung cancer characterization and staging, and in the evaluation of mediastinal and pleural pathology. Ongoing research opens a door to noninvasive evaluation of heart fibers by means of diffusion-tensor imaging.

Mitochondrial DNA sequences are present inside nuclear DNA in rat tissues and increase with age.

Mitochondrial DNA (mtDNA) mutations increase with age. However, the number of cells with predominantly mutated mtDNA is small in old animals. Here a new hypothesis is proposed: mtDNA fragments may insert into nuclear DNA contributing to aging and related diseases by alterations in the nucleus.

Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria.

Eighty percent dietary methionine restriction (MetR) in rodents (without calorie restriction), like dietary restriction (DR), increases maximum longevity and strongly decreases mitochondrial reactive oxygen species (ROS) production and oxidative stress. Eighty percent MetR also lowers the degree of membrane fatty acid unsaturation in rat liver. Mitochondrial ROS generation and the degree of fatty acid unsaturation are the only two known factors linking oxidative stress with longevity in vertebrates.