Phosphoinositide signaling in the nucleus: Impacts on chromatin and transcription regulation.

Phosphoinositides also called Polyphosphoinositides (PPIns) are small lipid messengers with established key roles in organelle trafficking and cell signaling in response to physiological and environmental inputs. Besides their well-described functions in the cytoplasm, accumulating evidences pointed to PPIns involvement in transcription and chromatin regulation. Through the description of previous and recent advances of PPIns implication in transcription, this review highlights key discoveries on how PPIns modulate nuclear factors activity and might impact chromatin to modify gene expression.

COVID-19 vaccine effectiveness against symptomatic infection and hospitalisation in Belgium, July 2021 to May 2022.

BackgroundThe Belgian COVID-19 vaccination campaign aimed to reduce disease spread and severity.AimWe estimated SARS-CoV-2 variant-specific vaccine effectiveness against symptomatic infection (VEi) and hospitalisation (VEh), given time since vaccination and prior infection.MethodsNationwide healthcare records from July 2021 to May 2022 on testing and vaccination were combined with a clinical hospital survey.

Predicting COVID-19 progression in hospitalized patients in Belgium from a multi-state model.

Objectives: To adopt a multi-state risk prediction model for critical disease/mortality outcomes among hospitalised COVID-19 patients using nationwide COVID-19 hospital surveillance data in Belgium.

Materials And Methods: Information on 44,659 COVID-19 patients hospitalised between March 2020 and June 2021 with complete data on disease outcomes and candidate predictors was used to adopt a multi-state, multivariate Cox model to predict patients' probability of recovery, critical [transfer to intensive care units (ICU)] or fatal outcomes during hospital stay.

Results: Median length of hospital stay was 9 days (interquartile range: 5-14).

Investigating COVID-19 Vaccine Impact on the Risk of Hospitalisation through the Analysis of National Surveillance Data Collected in Belgium.

The national vaccination campaign against SARS-CoV-2 started in January 2021 in Belgium. In the present study, we aimed to use national hospitalisation surveillance data to investigate the recent evolution of vaccine impact on the risk of COVID-19 hospitalisation. We analysed aggregated data from 27,608 COVID-19 patients hospitalised between October 2021 and February 2022, stratified by age category and vaccination status.

Clinical Severity of SARS-CoV-2 Omicron Variant Compared with Delta among Hospitalized COVID-19 Patients in Belgium during Autumn and Winter Season 2021-2022.

This retrospective multi-center matched cohort study assessed the risk for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality in hospitalized patients when infected with the Omicron variant compared to when infected with the Delta variant. The study is based on a causal framework using individually-linked data from national COVID-19 registries. The study population consisted of 954 COVID-19 patients (of which, 445 were infected with Omicron) above 18 years old admitted to a Belgian hospital during the autumn and winter season 2021-2022, and with available viral genomic data.

Severity of infection with the SARS-CoV-2 B.1.1.7 lineage among hospitalized COVID-19 patients in Belgium.

Introduction: The pathogenesis of COVID-19 depends on the interplay between host characteristics, viral characteristics and contextual factors. Here, we compare COVID-19 disease severity between hospitalized patients in Belgium infected with the SARS-CoV-2 variant B.1.

A Digital Case-Finding Algorithm for Diagnosed but Untreated Hepatitis C: A Tool for Increasing Linkage to Treatment and Cure.

Background And Aims: Although chronic HCV infection increases mortality, thousands of patients remain diagnosed-but-untreated (DBU). We aimed to (1) develop a DBU phenotyping algorithm, (2) use it to facilitate case finding and linkage to care, and (3) identify barriers to successful treatment.

Approach And Results: We developed a phenotyping algorithm using Java and SQL and applied it to ~2.

KDM5A and KDM5B histone-demethylases contribute to HU-induced replication stress response and tolerance.

KDM5A and KDM5B histone-demethylases are overexpressed in many cancers and have been involved in drug tolerance. Here, we describe that KDM5A, together with KDM5B, contribute to replication stress (RS) response and tolerance. First, they positively regulate RRM2, the regulatory subunit of ribonucleotide reductase.

Prey colonization in freshwater landscapes can be stimulated or inhibited by the proximity of remote predators.

Recent findings suggest that the colonization of habitat patches may be affected by the quality of surrounding patches. For instance, patches that lack predators may be avoided when located near others with predators, a pattern known as risk contagion. Alternatively, predator avoidance might also redirect dispersal towards nearby predator-free patches resulting in so-called habitat compression.

Automated phenotyping of patients with non-alcoholic fatty liver disease reveals clinically relevant disease subtypes.

Non-alcoholic fatty liver disease (NAFLD) is a complex heterogeneous disease which affects more than 20% of the population worldwide. Some subtypes of NAFLD have been clinically identified using hypothesis-driven methods. In this study, we used data mining techniques to search for subtypes in an unbiased fashion.

The histone demethylase JMJD2A/KDM4A links ribosomal RNA transcription to nutrients and growth factors availability.

The interplay between methylation and demethylation of histone lysine residues is an essential component of gene expression regulation and there is considerable interest in elucidating the roles of proteins involved. Here we report that histone demethylase KDM4A/JMJD2A, which is involved in the regulation of cell proliferation and is overexpressed in some cancers, interacts with RNA Polymerase I, associates with active ribosomal RNA genes and is required for serum-induced activation of rDNA transcription. We propose that KDM4A controls the initial stages of transition from 'poised', non-transcribed rDNA chromatin into its active form.

Intubation patterns and outcomes in patients with computed tomography-verified traumatic brain injury.

Background: Studies evaluating traumatic brain injury (TBI) patients have shown an association between prehospital (PH) intubation and worse outcomes. However, previous studies have used surrogates, e.g.

Histone demethylases in chromatin cross-talks.

The 'histone code' hypothesis states that chromatin-based regulation of nuclear processes such as transcription is brought about by the combination of distinct modifications (histone marks) at specific loci. Its correct establishment involves chromatin cross-talks, ensuring an ordered and concerted deposition/removal of a particular set of modifications that act together to give the correct transcriptional outcome. Histone methylation on lysine residues can negatively or positively impact on gene transcription, depending on the residue and on its degree of methylation.

A new isoform of the histone demethylase JMJD2A/KDM4A is required for skeletal muscle differentiation.

In proliferating myoblasts, muscle specific genes are silenced by epigenetic modifications at their promoters, including histone H3K9 methylation. Derepression of the promoter of the gene encoding the myogenic factor myogenin (Myog) is key for initiation of muscle differentiation. The mechanism of H3K9 demethylation at the Myog promoter is unclear, however.

Prospective identification of patients at risk for massive transfusion: an imprecise endeavor.

Most retrospective studies evaluating fresh-frozen plasma:packed red blood cell ratios in trauma patients requiring massive transfusion (MT) are limited by survival bias. As prospective resource-intensive studies are being designed to better evaluate resuscitation strategies, it is imperative that patients with a high likelihood of MT are identified early. The objective of this study was to develop a predictive model for MT in civilian trauma patients.

Image-guided methods for biopsy of suspicious breast lesions.

The widespread use of breast imaging has resulted in the increased detection of clinically occult suspicious breast lesions. Between 1999 and 2004 the number of breast biopsies in the United States has increased steadily. The armamentarium of methods to biopsy suspicious breast lesions has also increased significantly since the early 1990s with technological advancements for both surgical breast biopsy and percutaneous image guided breast biopsies.

Identifying risk for massive transfusion in the relatively normotensive patient: utility of the prehospital shock index.

Background: In the prehospital environment, the failure of medical providers to recognize latent physiologic derangement in patients with compensated shock may risk undertriage. We hypothesized that the shock index (SI; heart rate divided by systolic blood pressure [SBP]), when used in the prehospital setting, could facilitate the identification of such patients. The objective of this study was to assess the association between the prehospital SI and the risk of massive transfusion (MT) in relatively normotensive blunt trauma patients.

Duration of red cell storage influences mortality after trauma.

Background: Although previous studies have identified an association between the transfusion of relatively older red blood cells (RBCs) (storage ≥ 14 days) and adverse outcomes, they are difficult to interpret because the majority of patients received a combination of old and fresh RBC units. To overcome this limitation, we compared in-hospital mortality among patients who received exclusively old versus fresh RBC units during the first 24 hours of hospitalization.

Methods: Patients admitted to a Level I trauma center between January 2000 and May 2009 who received ≥ 1 unit of exclusively old (≥ 14 days) vs.

Effects of virtual reality simulator training method and observational learning on surgical performance.

Background: Virtual reality (VR) simulators and Web-based instructional videos are valuable supplemental training resources in surgical programs, but it is unclear how to optimally integrate them into minimally invasive surgical training.

Methods: Medical students were randomized to proficiency-based training on VR laparoscopy and endoscopy simulators by two different methods: proctored training (automated simulator feedback plus human expert feedback) or independent training (simulator feedback alone). After achieving simulator proficiency, trainees performed a series of laparoscopic and endoscopic tasks in a live porcine model.

Retention of colonoscopy skills after virtual reality simulator training by independent and proctored methods.

Virtual reality (VR) simulators may enhance surgical resident colonoscopy skills, but the duration of skill retention and the effects of different simulator training methods are unknown. Medical students participating in a randomized trial of independent (automated simulator feedback only) versus proctored (human expert feedback plus simulator feedback) simulator training performed a standardized VR colonoscopy scenario at baseline, at the end of training (posttraining), and after a median 4.5 months without practice (retention).

Computed tomography identification of latent pseudoaneurysm after blunt splenic injury: pathology or technology?

Background: Serial computed tomography (CT) imaging of blunt splenic injury can identify the latent formation of splenic artery pseudoaneurysms (PSAs), potentially contributing to improved success in nonoperative management. However, it remains unclear whether the delayed appearance of such PSAs is truly pathophysiologic or attributable to imaging quality and timing. The objective of this study was to evaluate the influence of recent advancements in imaging technology on the incidence of the latent PSA.