Actionable Variants of Unknown Significance in Inherited Arrhythmogenic Syndromes: A Further Step Forward in Genetic Diagnosis.

Inherited arrhythmogenic syndromes comprise a heterogenic group of genetic entities that lead to malignant arrhythmias and sudden cardiac death. Genetic testing has become crucial to understand the disease etiology and allow for the early identification of relatives at risk; however, it requires an accurate interpretation of the data to achieve a clinically actionable outcome. This is particularly challenging for the large number of rare variants obtained by current high-throughput techniques, which are mostly classified as of unknown significance.

The talk debrief experience: Intervention in prehospital personnel care during the Covid-19 pandemic.

This study focused on the TALK Debrief Experience in the prehospital personnel ( = 1521) of a western Spanish healthcare region during the COVID-19 Pandemic. The study aimed to apply the TALK clinical debriefing intervention to out-of-hospital clinical staff during pandemics; identify their emotions, thoughts, coping strategies, and solution proposals; determine their demands for improving well-being and coping ability; and disseminate valuable knowledge for addressing trauma in similar situations. The study employed a qualitative methodology within a participatory action research (PAR) framework, conducting group discussions ( = 375) and employing the TALK clinical debriefing method as the guiding framework for the sessions.

Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels.

PSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles) tsRNAs (tRNA-derived small RNAs) as PCa indicators.

Genotyping Hepatitis B virus by Next-Generation Sequencing: Detection of Mixed Infections and Analysis of Sequence Conservation.

Our aim was to develop an accurate, highly sensitive method for HBV genotype determination and detection of genotype mixtures. We examined the preS and 5' end of the HBV X gene (5X) regions of the HBV genome using next-generation sequencing (NGS). The 1852 haplotypes obtained were subjected to genotyping via the Distance-Based discrimination method (DB Rule) using two sets of 95 reference sequences of genotypes A-H.

In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis.

Lung-resident mesenchymal stem cells (LR-MSC) are thought to participate in idiopathic pulmonary fibrosis (IPF) by differentiating into myofibroblasts. On the other hand, LR-MSC in IPF patients present senescence-related features. It is unclear how they respond to a profibrotic environment.

Evolution of Pharmacological Treatments and Associated Costs for Multiple Myeloma in the Public Healthcare System of Catalonia: A Retrospective Observational Study.

(1) Background: Our understanding of and treatment for multiple myeloma (MM) has advanced significantly, and new pharmacological treatments have promising benefits but high price tags. This study analyzes prescription patterns and pharmaceutical expenditure for MM treatments in Catalonia's public healthcare system over eight years. (2) Methods: A retrospective observational study examined MM treatment data from 2015 to 2022 in Catalonia, using healthcare registries from the Catalan Health Service to collect information on patients, medicines used, and treatment costs.

3'IsomiR Species Composition Affects Reliable Quantification of miRNA/isomiR Variants by Poly(A) RT-qPCR: Impact on Small RNA-Seq Profiling Validation.

Small RNA-sequencing (small RNA-seq) has revealed the presence of small RNA-naturally occurring variants such as microRNA (miRNA) isoforms or isomiRs. Due to their small size and the sequence similarity among miRNA isoforms, their validation by RT-qPCR is challenging. We previously identified two miR-31-5p isomiRs-the canonical and a 3'isomiR variant (3' G addition)-which were differentially expressed between individuals with azoospermia of different origin.

Current Approach in the Management of Secondary Immunodeficiency in Patients with Hematological Malignancies: Spanish Expert Consensus Recommendations.

A Delphi-based survey was designed to assess the opinions of clinical hematologists (n = 17) and clinical immunologists (n = 18) from across Spain on secondary immunodeficiencies (SID) in the management of oncohematological patients. There was 100% agreement on the need to have available guidelines for the management of immunodeficiency in hematological patients; to perform a baseline immunological evaluation in patients with chronic lymphocytic leukemia (CLL), multiple myeloma (MM), lymphoma and hematopoietic stem cell transplantation (HSCT) recipients; and to quantify serum IgG, IgA and IgM levels when SID is suspected. More than 90% agreed on the need for active immunization against seasonal influenza and H1N1, pneumococcus and .

SWI/SNF Complex Alterations in Tumors with Rhabdoid Features: Novel Therapeutic Approaches and Opportunities for Adoptive Cell Therapy.

The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex is one of the most remarkably altered epigenetic regulators in cancer. Pathogenic mutations in genes encoding SWI/SNF-related proteins have been recently described in many solid tumors, including rare and aggressive malignancies with rhabdoid features with no standard therapies in advanced or metastatic settings. In recent years, clinical trials with targeted drugs aimed at restoring its function have shown discouraging results.

Management of patients on antithrombotic therapy with severe infections: a joint clinical consensus statement of the ESC Working Group on Thrombosis, the ESC Working Group on Atherosclerosis and Vascular Biology, and the International Society on Thrombosis and Haemostasis.

Patients with severe infections and a pre-existing indication for antithrombotic therapy, i.e. antiplatelet agents, anticoagulant drugs, or their combinations, require integrated clinical counselling among coagulation, infectious disease, and cardiology specialists, due to sepsis-induced coagulopathy that frequently occurs.

An organoid-based CRISPR-Cas9 screen for regulators of intestinal epithelial maturation and cell fate.

Generation of functionally mature organs requires exquisite control of transcriptional programs governing cell state transitions during development. Despite advances in understanding the behavior of adult intestinal stem cells and their progeny, the transcriptional regulators that control the emergence of the mature intestinal phenotype remain largely unknown. Using mouse fetal and adult small intestinal organoids, we uncover transcriptional differences between the fetal and adult state and identify rare adult-like cells present in fetal organoids.

Prolonged vs short-term infusion of β-lactam antibiotics for the treatment of febrile neutropenia: A systematic review and meta-analysis.

Background: The optimisation of the use of β-lactam antibiotics (BLA) via prolonged infusions in life-threatening complications such as febrile neutropenia (FN) is still controversial. This systematic review and meta-analysis aim to evaluate the efficacy of this strategy in onco-haematological patients with FN.

Methods: A systematic search was performed of PubMed, Web of Science, Cochrane, EMBASE, World Health Organization, and ClinicalTrials.

Use of phytosterol-fortified foods to improve LDL cholesterol levels: A systematic review and meta-analysis.

Aims: The main objective was to assess if foods fortified with phytosterols (PS), including plant sterols and plant stanols, reduce low-density lipoprotein cholesterol (LDL-C) concentrations. The secondary objective was to determine the impact of different factors related to PS administration.

Data Synthesis: The search was carried out in MEDLINE, EMBASE, Web of Science, Scopus and The Cochrane Central Register of Controlled Trials (CENTRAL) databases up to March 2023.

Development of a Standardized Method for Measuring Bioadhesion and Mucoadhesion That Is Applicable to Various Pharmaceutical Dosage Forms.

Although some methods for measuring bioadhesion/mucoadhesion have been proposed, a standardized method is not yet available. This is expected to hinder systematic comparisons of results across studies. This study aimed to design a single/systematic in vitro method for measuring bioadhesion/mucoadhesion that is applicable to various pharmaceutical dosage forms.

Towards a Mechanistic Model of Tau-Mediated Pathology in Tauopathies: What Can We Learn from Cell-Based In Vitro Assays?

Tauopathies are a group of neurodegenerative diseases characterized by the hyperphosphorylation and deposition of tau proteins in the brain. In Alzheimer's disease, and other related tauopathies, the pattern of tau deposition follows a stereotypical progression between anatomically connected brain regions. Increasing evidence suggests that tau behaves in a "prion-like" manner, and that seeding and spreading of pathological tau drive progressive neurodegeneration.

Differentially Aquaporin 5 Expression in Submandibular Glands and Cerebral Cortex in Alzheimer's Disease.

Impaired brain clearance mechanisms may result in the accumulation of aberrant proteins that define Alzheimer's disease (AD). The water channel protein astrocytic aquaporin 4 (AQP4) is essential for brain amyloid-β clearance, but it is known to be abnormally expressed in AD brains. The expression of AQPs is differentially regulated during diverse brain injuries, but, whereas AQP4 expression and function have been studied in AD, less is known about AQP5.

Adopting a High-Polyphenolic Diet Is Associated with an Improved Glucose Profile: Prospective Analysis within the PREDIMED-Plus Trial.

Previous studies suggested that dietary polyphenols could reduce the incidence and complications of type-2 diabetes (T2D); although the evidence is still limited and inconsistent. This work analyzes whether changing to a diet with a higher polyphenolic content is associated with an improved glucose profile. At baseline, and at 1 year of follow-up visits, 5921 participants (mean age 65.

Public Perceptions of the Role of Lifestyle Factors in Cancer Development: Results from the Spanish Onco-Barometer 2020.

The European Code against Cancer recommends not to smoke, to avoid alcohol consumption, to eat a healthy diet, and maintain a healthy weight to prevent cancer. To what extent is the public aware of the influence of these lifestyle factors on cancer development? The goal of the current study was to describe the perceived influence of four lifestyle factors (tobacco, alcohol, diet, and weight) on cancer development in the general population and identify factors related to low perceptions of influence. We analyzed data from the 2020 Onco-barometer (n = 4769), a representative population-based survey conducted in Spain.

Aberrant Splicing in Breast Cancer: Identification of Splicing Regulatory Elements and Minigene-Based Evaluation of 53 DNA Variants.

loss-of-function variants increase lifetime risk of breast and ovarian cancer. Splicing disruption is a frequent pathogenic mechanism associated with variants in susceptibility genes. Herein, we have assessed the splicing and clinical impact of splice-site and exonic splicing enhancer (ESE) variants identified through the study of ~113,000 women of the BRIDGES cohort.

Cell therapy with hiPSC-derived RPE cells and RPCs prevents visual function loss in a rat model of retinal degeneration.

Photoreceptor loss is the principal cause of blindness in retinal degenerative diseases (RDDs). Whereas some therapies exist for early stages of RDDs, no effective treatment is currently available for later stages, and once photoreceptors are lost, the only option to rescue vision is cell transplantation. With the use of the Royal College of Surgeons (RCS) rat model of retinal degeneration, we sought to determine whether combined transplantation of human-induced pluripotent stem cell (hiPSC)-derived retinal precursor cells (RPCs) and retinal pigment epithelial (RPE) cells was superior to RPE or RPC transplantation alone in preserving retinal from degeneration.

Assessing Effectiveness of Colonic and Gynecological Risk Reducing Surgery in Lynch Syndrome Individuals.

Background: Colorectal (CRC) and endometrial cancer (EC) are the most common types of cancer in Lynch syndrome (LS). Risk reducing surgeries (RRS) might impact cancer incidence and mortality. Our objectives were to evaluate cumulative incidences of CRC, gynecological cancer and all-cause mortality after RRS in LS individuals.

Smelling the Dark Proteome: Functional Characterization of PITH Domain-Containing Protein 1 (C1orf128) in Olfactory Metabolism.

The Human Proteome Project (HPP) consortium aims to functionally characterize the dark proteome. On the basis of the relevance of olfaction in early neurodegeneration, we have analyzed the dark proteome using data mining in public resources and omics data sets derived from the human olfactory system. Multiple dark proteins localize at synaptic terminals and may be involved in amyloidopathies such as Alzheimer's disease (AD).

Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis.

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive muscle paralysis due to the degeneration of upper and lower motor neurons. Recent studies point out an involvement of the non-motor axis during disease progression. Despite smell impairment being considered a potential non-motor finding in ALS, the pathobiochemistry at the olfactory level remains unknown.

Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Spain: Clinical and Genetic Characterization.

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations.