Sacubitril-Valsartan in Cancer Therapy-Induced Heart Failure: A Systematic Review and Meta-Analysis of Functional and Hemodynamic Parameters.

Background: Cancer therapy-induced cardiotoxicity (CTRCD), in the form of heart failure with reduced ejection fraction (HFrEF), is being increasingly recognized. However, the potential benefits of sacubitril/valsartan (S/V) in managing HFrEF secondary to CTRCD remain unclear.

Objective: We performed a systematic review and meta-analysis to assess the effectiveness of S/V in preventing cardiotoxicity.

Systematic screening of enhancer-blocking insulators in Drosophila identifies their DNA sequence determinants.

Long-range transcriptional activation of gene promoters by abundant enhancers in animal genomes calls for mechanisms to limit inappropriate regulation. DNA elements called insulators serve this purpose by shielding promoters from an enhancer when interposed. Unlike promoters and enhancers, insulators have not been systematically characterized due to lacking high-throughput screening assays, and questions regarding how insulators are distributed and encoded in the genome remain.

Protocol for detecting genomic insulators in Drosophila using insulator-seq, a massively parallel reporter assay.

Genomic insulators are DNA elements that prevent transcriptional activation of a promoter by an enhancer when interposed. We present a protocol for insulator-seq that enables high-throughput screening of genomic insulators using a plasmid-based massively parallel reporter assay in Drosophila cultured cells. We describe steps for insulator reporter plasmid library generation, transient transfection into cultured cells, and sequencing library preparation and provide a pipeline for data analysis.

Enhancer-promoter interactions become more instructive in the transition from cell-fate specification to tissue differentiation.

To regulate expression, enhancers must come in proximity to their target gene. However, the relationship between the timing of enhancer-promoter (E-P) proximity and activity remains unclear, with examples of uncoupled, anticorrelated and correlated interactions. To assess this, we selected 600 characterized enhancers or promoters with tissue-specific activity in Drosophila embryos and performed Capture-C in FACS-purified myogenic or neurogenic cells during specification and tissue differentiation.

Chromosome-level organization of the regulatory genome in the Drosophila nervous system.

Previous studies have identified topologically associating domains (TADs) as basic units of genome organization. We present evidence of a previously unreported level of genome folding, where distant TAD pairs, megabases apart, interact to form meta-domains. Within meta-domains, gene promoters and structural intergenic elements present in distant TADs are specifically paired.

Analysis of possible risk predictors in patients with coronavirus disease 2019: a retrospective cohort study.

Objective: This study aimed to analyze the clinical-epidemiological profile, possible risk predictors, and outcomes of patients with coronavirus disease 2019 admitted to the ward of a tertiary care hospital in southern Brazil. Specifically, we describe the demographic characteristics, comorbidities, baseline laboratory findings, clinical course, and survival of these patients.

Methods: This is an observational, retrospective cohort study, performed from January to March 2022, on medical records of patients hospitalized between April 2020 and December 2021 in the coronavirus disease 2019 ward of a tertiary hospital in southern Brazil.

Predictive value of neutrophil-to-lymphocyte ratio and neutrophil-to-monocyte ratio in severe traumatic brain injury: a retrospective cohort.

Background: The neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), the lymphocyte-monocyte ratio (LMR), the neutrophil-monocyte ratio (NMR) and the systemic immune inflammation index (SII) are associated with clinical outcomes in oncological diseases, cardiovascular diseases, infectious / inflammatory diseases, endocrinological, pulmonary and brain injuries. Here, we investigate its association with hospital mortality in patients with severe traumatic brain injury.

Methods: We retrospectively reviewed clinical data from patients with severe traumatic brain injury (sTBI) who were treated in our department between January 2015 and December 2020.

Essential role of Cp190 in physical and regulatory boundary formation.

Boundaries in animal genomes delimit contact domains with enhanced internal contact frequencies and have debated functions in limiting regulatory cross-talk between domains and guiding enhancers to target promoters. Most mammalian boundaries form by stalling of chromosomal loop-extruding cohesin by CTCF, but most boundaries form CTCF independently. However, how CTCF-independent boundaries form and function remains largely unexplored.

CTCF loss has limited effects on global genome architecture in Drosophila despite critical regulatory functions.

Vertebrate genomes are partitioned into contact domains defined by enhanced internal contact frequency and formed by two principal mechanisms: compartmentalization of transcriptionally active and inactive domains, and stalling of chromosomal loop-extruding cohesin by CTCF bound at domain boundaries. While Drosophila has widespread contact domains and CTCF, it is currently unclear whether CTCF-dependent domains exist in flies. We genetically ablate CTCF in Drosophila and examine impacts on genome folding and transcriptional regulation in the central nervous system.

The Role of Insulation in Patterning Gene Expression.

Development is orchestrated by regulatory elements that turn genes ON or OFF in precise spatial and temporal patterns. Many safety mechanisms prevent inappropriate action of a regulatory element on the wrong gene promoter. In flies and mammals, dedicated DNA elements (insulators) recruit protein factors (insulator binding proteins, or IBPs) to shield promoters from regulatory elements.

The Insulator Protein CTCF Is Required for Correct Gene Expression, but Not for Embryonic Development in .

Insulator binding proteins (IBPs) play an important role in regulating gene expression by binding to specific DNA sites to facilitate appropriate gene regulation. There are several IBPs in , each defined by their ability to insulate target gene promoters in transgenic assays from the activating or silencing effects of neighboring regulatory elements. Of these, only CCCTC-binding factor (CTCF) has an obvious ortholog in mammals.

Antimicrobial stewardship through telemedicine and its impact on multi-drug resistance.

Introduction: Telemedicine technologies are increasingly being incorporated into infectious disease practice. We aimed to demonstrate the impact of antimicrobial stewardship through telemedicine on bacterial resistance rates.

Methods: We conducted a quasi-experimental study in a 220-bed hospital in southern Brazil.

Routine operation theatre extubation after cardiac surgery in the elderly.

Objectives: The aim was to analyse in-hospital outcomes of patients over 70 years of age undergoing routine immediate operation theatre (OT) extubation after on-pump or off-pump cardiac surgery.

Methods: A retrospective analysis was performed of prospectively collected data over a 4-year period (2011-14) from elderly patients undergoing early extubation after cardiac surgery at a single institution. All patients over 70 years were considered eligible for immediate OT or intensive care unit (ICU) early extubation after meeting specific criteria.

A critical perspective of the diverse roles of O-GlcNAc transferase in chromatin.

O-linked β-N-Acetylglucosamine (O-GlcNAc) is a posttranslational modification that is catalyzed by O-GlcNAc transferase (Ogt) and found on a plethora of nuclear and cytosolic proteins in animals and plants. Studies in different model organisms revealed that while O-GlcNAc is required for selected processes in Caenorhabditis elegans and Drosophila, it has evolved to become required for cell viability in mice, and this has challenged investigations to identify cellular functions that critically require this modification in mammals. Nevertheless, a principal cellular process that engages O-GlcNAcylation in all of these species is the regulation of gene transcription.

O-GlcNAcylation prevents aggregation of the Polycomb group repressor polyhomeotic.

The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure to repress Polycomb target genes. The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro.

Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements.

Polycomb group (PcG) protein complexes repress developmental regulator genes by modifying their chromatin. How different PcG proteins assemble into complexes and are recruited to their target genes is poorly understood. Here, we report the crystal structure of the core of the Drosophila PcG protein complex Pleiohomeotic (Pho)-repressive complex (PhoRC), which contains the Polycomb response element (PRE)-binding protein Pho and Sfmbt.

Impact of human activities on the geomagnetic field of Antarctica: a high resolution aeromagnetic survey over Mario Zucchelli Station.

Environmental protection of Antarctica is a fundamental principle of the Antarctic Treaty. Impact assessment and significance evaluation are due for every human activity on the remote continent. While chemical and biological contaminations are widely studied, very little is known about the electromagnetic pollution levels.

The role of the histone H2A ubiquitinase Sce in Polycomb repression.

Polycomb group (PcG) proteins exist in multiprotein complexes that modify chromatin to repress transcription. Drosophila PcG proteins Sex combs extra (Sce; dRing) and Posterior sex combs (Psc) are core subunits of PRC1-type complexes. The Sce:Psc module acts as an E3 ligase for monoubiquitylation of histone H2A, an activity thought to be crucial for repression by PRC1-type complexes.

Essential role of the glycosyltransferase sxc/Ogt in polycomb repression.

Polycomb group proteins are conserved transcriptional repressors that control animal and plant development. Here, we found that the Drosophila Polycomb group gene super sex combs (sxc) encodes Ogt, the highly conserved glycosyltransferase that catalyzes the addition of N-acetylglucosamine (GlcNAc) to proteins in animals and plants. Genome-wide profiling in Drosophila revealed that GlcNAc-modified proteins are highly enriched at Polycomb response elements.

Impact of the implementation of telemanagement on a disease management program in an elderly heart failure cohort.

The purpose of the present investigation is to examine the impact of a telemanagement component on an outpatient disease management program in patients with heart failure (HF). A total of 282 patients in whom HF was diagnosed and who were enrolled in an outpatient HF program were included in this analysis. One hundred fifty-eight patients additionally participated in a self-directed telemanagement component.

Alternation of atrial cycle length in supraventricular tachycardia.

Nine cases of alternation of the atrial cycles during supraventricular tachycardia are presented, three of which were manifestly due to digitalis toxicity. They presented the following features: absence of 1/1 conduction, upright P waves in Lead II, atrial rates of 156-218. When alternation disappeared, the atrium adopted the longest of the previously inscribed cycles.

Electrophysiological changes in the canine atrium and ventricle during progressive hyperkalaemia: electrocardiographical correlates and the in vivo validation of in vitro predictions.

The electrophysiological response to hyperkalaemia was reinvestigated in the whole dog for several reasons including: the paucity of comparative electrophysiological and electrocardiographical studies in which atrial and ventricular tissues were simultaneously investigated; the contrast between the clarity of findings in previous in vitro studies as compared with the rather conflicting results in earlier in vivo investigations; and the difficulty in validating the extrapolation from in vitro results and theory to the in vivo situation because of deficiences in the literature. Biphasic alterations in atrial and ventricular conduction times as well as excitability in response to progressively increasing hyperkalaemia were documented. The alterations in conduction times were reflected quite accurately by relevant electrocardiographical changes.