Clinical Pharmacist-Led Collaboration of Multiple Clinical Professions Model Focusing on Continuity of Pharmacotherapy: Japanese Version of the Lund Integrated Medicines Management (LIMM) Model.

(1) Background: In general, it is known that continuity of care can contribute to an increase in patient satisfaction, reduce health care costs, and improve patient outcomes. A guarantee of continuity in pharmacotherapy is a big challenge facing Japanese health care as a system that encourages cooperation/collaboration for pharmacists with other health care professions is currently lacking. (2) Method: This is a narrative review.

The polycomb protein complex interacts with GATA-6/PPARα to inhibit α-MHC expression.

Transcription factors collaborate with epigenetic regulatory factors to orchestrate cardiac differentiation for heart development, but the underlying mechanism is not fully understood. Here, we report that GATA-6 induces cardiac differentiation but peroxisome proliferator-activated receptor α (PPARα) reverses GATA-6-induced cardiac differentiation, possibly because GATA-6/PPARα recruits the polycomb protein complex containing EZH2/Ring1b/BMI1 to the promoter of the cardiac-specific α-myosin heavy chain (α-MHC) gene and suppresses α-MHC expression, which ultimately inhibits cardiac differentiation. Furthermore, Ring1b ubiquitylates PPARα and GATA-6.

Enhancing cardiac regeneration: direct reprogramming of fibroblasts into myocardial-like cells using extracellular vesicles secreted by cardiomyocytes.

To investigate the promoting effect of extracellular vesicles derived from myocardial cells (CM-EVs) on the reprogramming of cardiac fibroblasts (CFs) into cardiomyocyte-like cells (iCMs) and their therapeutic effect on myocardial infarction (MI) in rats. Cell experiments: The differential adhesion method was used to obtain Sprague Dawley (SD) suckling rat CFs and cardiomyocytes (CMs), while the ultracentrifugation method was used to obtain CM-EVs. Transmission electron microscopy and nanoparticle tracking technology were used to analyze and determine the morphology and particle size of CM-EVs.

Patient characteristics in relation to opioid exposure in a chronic non-cancer pain population.

Objectives: The efficacy of long-term opioid therapy (LTOT) in treating patients with chronic non-cancer pain (CnCP) is questionable, and the potential risks of adverse effects are well established. The aims were as follows: (1) compare characteristics in patients exposed to LTOT vs non-exposed. (2) Regarding opioid-exposed patients, describe characteristics of patients with risk factors for opioid use disorder or overdose in relation to opioid dosage.

Malignant transformation of nephrogenic adenoma of the bladder: case report and literature review.

Background: Nephrogenic adenoma (NA) is a rare benign tumor that can develop at any site of the urinary system, with the bladder being the most common, followed by the urethra, ureters, renal pelvises, etc. Currently, it is unclear what the pathogenesis of NA is. This study discussed a rare case of malignant transformation from NA to mesonephric adenocarcinoma of the bladder.

Differential Control of T-Cell Subsets by Recombinant Human PLD2 in a Mouse Model of Allergic Asthma.

Background: Phospholipase D2 (PLD2) enzymes are expressed on the cytoplasmic membrane of bacteria, fungi, plants, and animals. Recently, extensive research has linked PLD2 to the chronic inflammatory activity of cells. Allergic asthma is a chronic airway inflammation disease.

Progressive chromatin rewiring by ETO2::GLIS2 revealed in a human iPSC model of pediatric leukemia initiation.

Pediatric acute myeloid leukemia frequently harbor fusion oncogenes associated with poor prognosis, including KMT2A, NUP98 and GLIS2 rearrangements. While murine models have demonstrated their leukemogenic activities, the steps from a normal human cell to leukemic blasts remain unclear. Here, we precisely reproduced the inversion of chromosome 16 resulting in ETO2::GLIS2 fusion in human induced pluripotent stem cells (iPSC).

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

Inhibition of DNA Methyltransferase DNMT1 Reverses Th2 Response Polarisation and Alleviates Allergic Rhinitis.

Background: Type 2 T helper (Th2) cells-mediated immune response plays vital roles in allergic rhinitis (AR), and DNA methylation is previously found to be closely related to AR development.

Aims: Our study aims to reveal the detail mechanism of DNA methylation affecting Th2 response in AR.

Methods: Mice were stimulated with ovalbumin (OVA) to induce AR symptoms, and CD4 T cells were subjected to Th2 induction culture.

Ginsenoside Rg1 attenuates Aβ-induced microglial cell apoptosis and inflammation in Alzheimer's disease via the GATA4/PDE4A/PI3K/AKT axis.

Ginsenoside Rg1 (Rg1) has been shown to treat a variety of human diseases, including Alzheimer's disease (AD). However, its mechanism in AD needs further investigation. Microglial cells (BV2) were treated with Aβ to induce AD cell models.

The GATA-3-dependent transcriptome and tumor microenvironment are regulated by eIF4E and XPO1 in T-cell lymphomas.

The transcription factor GATA-3 and the transcriptional program it regulates have emerged as oncogenic drivers across diverse T-cell lymphomas (TCL), many of which are resistant to conventional chemotherapeutic agents and characterized by recurrent losses of key tumor suppressor genes, including TP53 and PTEN, both of which are clients of the nuclear export protein XPO1. Here we demonstrated that XPO1 is highly expressed by malignant T cells expressing GATA-3 and by lymphoma-associated macrophages (LAM) within their tumor microenvironment (TME). Using complementary genetically engineered mouse (GEM) models, we demonstrated that TP53 and/or PTEN deficient TCL, and LAM within their TME, are sensitive to the selective XPO1 antagonist selinexor.

BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

Update on aspirin exacerbated respiratory disease with chronic rhinosinusitis.

Purpose Of Review: This review provides the current understanding on the mechanism, diagnosis, and treatment of aspirin exacerbated respiratory disease (AERD) with chronic rhinosinusitis (CRS).

Recent Findings: Updates focus on the current understanding of type 2 inflammation as a disease driver, alterations in gene expression in nasal polyps, and use of biologics in treating aspirin exacerbated respiratory disease. Recent findings include altered expression of GATA binding protein 3 (GATA3), interleukin (IL)-4, IL-5, and IL-17 in nasal polyps supports the current understanding that type 2 inflammation predominantly drives the pathophysiology of AERD with CRS.

LncRNA MIAT binding to GATA3 activates MAPK signaling pathway and influences bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) manifests in premature neonates with aberrant pulmonary function. Numerous long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of BPD. This study aims to elucidate the impact of the lncRNA myocardial infarction-associated transcript (MIAT) on the initiation and progression of BPD.

An update on epigenetic mechanisms in endometriosis.

The etiopathogenesis of endometriosis, a chronic debilitating disease affecting nearly 10% of women, has evaded elucidation until the recent epigenetic discoveries. Although still deemed multifactorial, endometriosis is likely predisposed in women with genetic and epigenetic alterations, which are activated by environmental factors. There are many epigenetic changes that have recently been associated with endometriosis: DNA methylation and phosphorylation, modifications to histones and non-coding RNA, and chromatin remodeling and organization.

To give or not give antibiotic prophylaxis for planned caesarean section: An assessment of risk of postpartum prescription of antibiotics depending on prophylaxis regimen.

Introduction: No national recommendation for antibiotic prophylaxis for planned caesarean section in Sweden exists. Swedish delivery units have chosen different strategies. Some units routinely administer antibiotic prophylaxis to all women for whom a caesarean section is planned, while other units give prophylactic antibiotics to risk groups only.

Registered nurses' experiences of communication with patients after the end-of-life breakpoint communication: A pilot interview study.

Purpose: Effective nurse-patient communication is demanding and essential when patients' treatment changes from curative to palliative approach. We aimed to illustrate nurses' experiences communicating with patients who have undergone end-of-life breakpoint communication.

Method: Six nurses from both haematology and oncology wards at a hospital in southern Sweden were interviewed.

Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer's disease, positive for plasma p-tau217.

Background: The spread of tau pathology closely correlates with the disease course and cognitive decline in Alzheimer's disease (AD). Tau-targeting immunotherapies are being developed to stop the spread of tau pathology and thus halt disease progression. In this post hoc analysis of the ADAMANT clinical trial, we examined the performance of AADvac1, an active immunotherapy targeting the microtubule-binding region (MTBR) of tau, in a subgroup of participants with elevated plasma p-tau217, indicating AD-related neuropathological changes.

Ovarian follicular flushing as a means of increasing oocyte yield and embryo production in cattle.

Context The number of developmentally competent cumulus-oocyte complexes (COCs) retrieved during Ovum Pick-Up (OPU) determines success in both bovine and human assisted reproduction. Follicular flushing for COC retrieval is practicsed widely in humans but not in cattle. Aims To determine the benefits of follicular flushing in cattle and assess the merits of a novel 16G double-lumen needle ('OxIVF') that flushes laterally to the needle shaft.

KMT2A regulates the autophagy-GATA4 axis through METTL3-mediated mA modification of ATG4a to promote NPCs senescence and IVDD progression.

Intervertebral disc degeneration (IVDD), a disease associated with ageing, is characterised by a notable increase in senescent nucleus pulposus cells (NPCs) as IVDD progresses. However, the specific mechanisms that regulate the senescence of NPCs remain unknown. In this study, we observed impaired autophagy in IVDD-NPCs, which contributed to the upregulation of NPCs senescence and the senescence-associated secretory phenotype (SASP).

The T cell response to SARS-CoV-2 mRNA vaccine in adults with high exposure to perfluoroalkyl substances from Ronneby, Sweden.

Background: Perfluoroalkyl substances (PFAS) have been associated with impaired antibody levels after childhood vaccinations and immunosuppressive effects in animals. However, the in vivo effects of PFAS on antigen specific human T cell responses have not been investigated in adults. In Ronneby, Sweden, the drinking water of one of the water works was previously highly contaminated with primarily perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS).

MSK ultrasound imaging-assisted clinical examination.

Musculoskeletal disorders are a significant global health concern, affecting over 1.71 billion individuals worldwide, with a considerable impact on quality of life and economic burden due to healthcare costs and productivity losses. In the United Kingdom, approximately one-third of the population suffers from musculoskeletal disorders, underscoring the need for effective diagnostic and management strategies.