Epigenetic-based differentiation therapy for Acute Myeloid Leukemia.

Despite the development of novel therapies for acute myeloid leukemia, outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia, their role in other acute myeloid leukemia subtypes needs to be explored. Here we identify and characterize two lysine deacetylase inhibitors, CM-444 and CM-1758, exhibiting the capacity to promote myeloid differentiation in all acute myeloid leukemia subtypes at low non-cytotoxic doses, unlike other commercial histone deacetylase inhibitors.

Transition transferases prime bacterial capsule polymerization.

Capsules are long-chain carbohydrate polymers that envelop the surfaces of many bacteria, protecting them from host immune responses. Capsule biosynthesis enzymes are potential drug targets and valuable biotechnological tools for generating vaccine antigens. Despite their importance, it remains unknown how structurally variable capsule polymers of Gram-negative pathogens are linked to the conserved glycolipid anchoring these virulence factors to the bacterial membrane.

Potential protective role of let-7d-5p in atherosclerosis progression reducing the inflammatory pathway regulated by NF-κB and vascular smooth muscle cells proliferation.

The prevalence of cardiovascular diseases (CVDs) is increasing in the last decades, even is the main cause of death in first world countries being atherosclerosis one of the principal triggers. Therefore, there is an urgent need to decipher the underlying mechanisms involved in atherosclerosis progression. In this respect, microRNAs dysregulation is frequently involved in the progression of multiple diseases including CVDs.

Twice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease.

Background: Sebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3-5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials.

Obtaining patient phenotypes in SARS-CoV-2 pneumonia, and their association with clinical severity and mortality.

Background: There exists consistent empirical evidence in the literature pointing out ample heterogeneity in terms of the clinical evolution of patients with COVID-19. The identification of specific phenotypes underlying in the population might contribute towards a better understanding and characterization of the different courses of the disease. The aim of this study was to identify distinct clinical phenotypes among hospitalized patients with SARS-CoV-2 pneumonia using machine learning clustering, and to study their association with subsequent clinical outcomes as severity and mortality.

FMR1 allelic complexity in premutation carriers provides no evidence for a correlation with age at amenorrhea.

Background: Premutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, defined as between 55 and 200 CGGs, have been implicated in fragile X-associated primary ovarian insufficiency (FXPOI). Only 20% of female premutation carriers develop early ovulatory dysfunction, the reason for this incomplete penetrance is unknown. This study validated the mathematical model in premutation alleles, after assigning each allele a score representing allelic complexity.

Conformation- and activation-based BRET sensors differentially report on GPCR-G protein coupling.

G protein-coupled receptors (GPCRs) regulate cellular signaling processes by coupling to diverse combinations of heterotrimeric G proteins composed of Gα, Gβ, and Gγ subunits. Biosensors based on bioluminescence resonance energy transfer (BRET) have advanced our understanding of GPCR functional selectivity. Some BRET biosensors monitor ligand-induced conformational changes in the receptor or G proteins, whereas others monitor the recruitment of downstream effectors to sites of G protein activation.

Normative Data Study of Verbal Fluency and Naming Tests in Elderly People in Costa Rica.

Objective: To generate normative data for the Verbal Fluency Test (VFT) and the Boston Naming Test (BNT) in the Costa Rican population.

Method: The sample consisted of 563 healthy older people (aged 59-90 years). Polynomial multiple regression analyses were run to evaluate the effects of the age, sex, and education variables on VFT and BNT scores.

Efficacy and safety of long-acting injectable oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis.

Background: Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear.

Objectives: To assess the relative medium- and long-term efficacy and safety of LAIs OAPs in the maintenance treatment of patients with early-phase SSDs.

Method: We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing LAIs and OAPs for the maintenance treatment of patients with early-phase-SSDs.

Identification of hypermucoviscous Klebsiella pneumoniae K1, K2, K54 and K57 capsular serotypes by Raman spectroscopy.

Antimicrobial resistance poses a significant challenge in modern medicine, affecting public health. Klebsiella pneumoniae infections compound this issue due to their broad range of infections and the emergence of multiple antibiotic resistance mechanisms. Efficient detection of its capsular serotypes is crucial for immediate patient treatment, epidemiological tracking and outbreak containment.

Computational method for designing vaccines applied to virus-like particles (VLPs) as epitope carriers.

Nonenveloped virus-like particles (VLPs) are self-assembled oligomeric structures composed of one or more proteins that originate from diverse viruses. Because these VLPs have similar antigenicity to the parental virus, they are successfully used as vaccines against cognate virus infection. Furthermore, after foreign antigenic sequences are inserted in their protein components (chimVLPs), some VLPs are also amenable to producing vaccines against pathogens other than the virus it originates from (these VLPs are named platform or epitope carrier).

Impact of HLA-B51 on Uveitis and Retinal Vasculitis: Data from the AIDA International Network Registries on Ocular Inflammatory Disorders.

Purpose: The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet's disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown.

Methods: Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time.

Mid-term clinical radiological results of the constrained condylar knee prosthesis in total knee revision.

Introduction: The aim of the present study is to analyze the clinical-radiological outcomes of patients undergoing knee prosthesis revision surgery using constrained condylar prosthesis (LCCK; Zimmer-Biomet).

Material And Methods: Retrospective study of 89 patients operated on between the years 2008 and 2020 with a minimum of 2 years of follow-up. Clinical outcomes were evaluated using the WOMAC Index score and KOOS scales.

Challenges faced by migrant seasonal agricultural farmworkers for food accessibility in Spain: A qualitative study.

Migrants who work seasonally in agriculture face living and working conditions that significantly impact their health. Some of these conditions are related to inadequate food access or food preservation and preparation hygiene. This study aimed to explore how migrant and seasonal agricultural farmworkers access food in Spain from the perspective of professionals supporting this population.

Impact of antibiotic prophylaxis in second-stage surgery in joint prosthesis infection treated with two-stage exchange. A multicenter case-control study.

Introduction: After two-stage exchange due to prosthetic joint infection (PJI), the new prosthesis carries a high risk of reinfection (RePJI). There isn`t solid evidence regarding the antibiotic prophylaxis in 2nd-stage surgery. The objective of this study is to describe what antibiotic prophylaxis is used in this surgery and evaluate its impact on the risk of developing RePJI.

Fluocinolone intravitreal implant (Iluvien) for macular edema secondary to immune recovery uveitis in patient with acute myeloid leukemia.

Purpose: To report the use of Fluocinolone intravitreal implant (Iluvien) for the treatment of persistent cystoid macular edema (CME) due to immune recovery uveitis syndrome in a patient with previous cytomegalovirus retinitis and acute myeloid leukemia.

Design: Case report.

Methods: The clinical history of a patient who received an Iluvien implant in one eye for the treatment of cystoid macular edema due to immune recovery uveitis syndrome, previously treated with peribulbar Triamcinolone and intravitreal Dexamethasone injections, was reviewed.

DNA methylation differences between the female and male X chromosomes in human brain.

The mechanisms of X chromosome inactivation suggest fundamental epigenetic differences between the female and male X chromosomes. However, DNA methylation studies often exclude the X chromosomes. In addition, many previous studies relied on techniques that examine non-randomly selected subsets of positions such as array-based methods, rather than assessing the whole X chromosome.

Factors influencing natural fecundity in fertile couples: a survey of puerperae and their partners.

Research Question: What is the fecundity rate among fertile couples, and which factors influence it?

Design: Retrospective study of all puerperae attending Cruces University Hospital Human Reproduction Unit over 9 months. An anonymous questionnaire was circulated to all patients, and 2510 valid completed questionnaires were collected. The main inclusion criterion was natural conception resulting in delivery.