Mycophenolate Mofetil Versus Prednisone for Induction Therapy in Steroid-Sensitive Idiopathic Nephrotic Syndrome in Children: An Observational Study.

Rationale & Objective: High-dose steroids are recommended for the induction of idiopathic nephrotic syndrome. The aim of this study was to compare standard induction therapy with Mycophenolate Mofetil (MMF). We hypothesized that MMF could be noninferior to steroids in maintaining steroid-induced remission.

An emerging paradigm in epigenetic marking: coordination of transcription and replication.

DNA replication and RNA transcription both utilize DNA as a template and therefore need to coordinate their activities. The predominant theory in the field is that in order for the replication fork to proceed, transcription machinery has to be evicted from DNA until replication is complete. If that does not occur, these machineries collide, and these collisions elicit various repair mechanisms which require displacement of one of the enzymes, often RNA polymerase, in order for replication to proceed.

Fibrosis-the tale of H3K27 histone methyltransferases and demethylases.

Fibrosis, or excessive scarring, is characterized by the emergence of alpha-smooth muscle actin (αSMA)-expressing myofibroblasts and the excessive accumulation of fibrotic extracellular matrix (ECM). Currently, there is a lack of effective treatment options for fibrosis, highlighting an unmet need to identify new therapeutic targets. The acquisition of a fibrotic phenotype is associated with changes in chromatin structure, a key determinant of gene transcription activation and repression.

RNA polymerase II associates with active genes during DNA replication.

The transcriptional machinery is thought to dissociate from DNA during replication. Certain proteins, termed epigenetic marks, must be transferred from parent to daughter DNA strands in order to maintain the memory of transcriptional states. These proteins are believed to re-initiate rebuilding of chromatin structure, which ultimately recruits RNA polymerase II (Pol II) to the newly replicated daughter strands.

Changes in nascent chromatin structure regulate activation of the pro-fibrotic transcriptome and myofibroblast emergence in organ fibrosis.

Cell reprogramming to a myofibroblast responsible for the pathological accumulation of extracellular matrix is fundamental to the onset of fibrosis. Here, we explored how condensed chromatin structure marked by H3K72me3 becomes modified to allow for activation of repressed genes to drive emergence of myofibroblasts. In the early stages of myofibroblast precursor cell differentiation, we discovered that H3K27me3 demethylase enzymes UTX/KDM6B creates a delay in the accumulation of H3K27me3 on nascent DNA revealing a period of decondensed chromatin structure This period of decondensed nascent chromatin structure allows for binding of pro-fibrotic transcription factor, Myocardin-related transcription factor A (MRTF-A) to nascent DNA.

Regional Antibiotic Delivery for Implanted Cardiovascular Electronic Device Infections.

Background: Present guidelines endorse complete removal of cardiovascular implantable electronic devices (pacemakers/defibrillators), including extraction of all intracardiac electrodes, not only for systemic infections, but also for localized pocket infections.

Objectives: The authors evaluated the efficacy of delivering continuous, in situ-targeted, ultrahigh concentration of antibiotics (CITA) into the infected subcutaneous device pocket, obviating the need for device/lead extraction.

Methods: The CITA group consisted of 80 patients with pocket infection who were treated with CITA during 2007-2021.

Acute kidney injury requiring kidney replacement therapy in childhood lupus nephritis: a cohort study of the Pediatric Nephrology Research Consortium and Childhood Arthritis and Rheumatology Research Alliance.

Background: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited.

Bacterial extracellular vesicles control murine norovirus infection through modulation of antiviral immune responses.

Human norovirus is the primary cause of non-bacterial gastroenteritis globally and is the second leading cause of diarrheal deaths in children in developing countries. However, effective therapeutics which prevent or clear norovirus infection are not yet available due to a lack of understanding regarding norovirus pathogenesis. Evidence shows that noroviruses can bind to the surface of commensal bacteria, and the presence of these bacteria alters both acute and persistent murine norovirus infection through the modulation of host immune responses.

Ambulatory Blood Pressure Patterns in Children, Adolescents, and Young Adults With Childhood-Onset Systemic Lupus Erythematosus and Normal Office Blood Pressure.

Objective: Cardiovascular disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Hypertension (HTN) and nondipping are modifiable risk factors for cardiovascular disease. Limited studies are available for childhood-onset SLE (cSLE).

Star-Peptide Polymers are Multi-Drug-Resistant Gram-Positive Bacteria Killers.

Antibiotic resistance in bacteria, especially Gram-positive bacteria like , is gaining considerable momentum worldwide and unless checked will pose a global health crisis. With few new antibiotics coming on the market, there is a need for novel antimicrobial materials that target and kill multi-drug-resistant (MDR) Gram-positive pathogens like methicillin-resistant (MRSA). In this study, using a novel mixed-bacteria antimicrobial assay, we show that the star-peptide polymers preferentially target and kill Gram-positive pathogens including MRSA.

Targeting Chemotherapy to Decondensed H3K27me3-Marked Chromatin of AML Cells Enhances Leukemia Suppression.

Despite treatment with intensive chemotherapy, acute myelogenous leukemia (AML) remains an aggressive malignancy with a dismal outcome in most patients. We found that AML cells exhibit an unusually rapid accumulation of the repressive histone mark H3K27me3 on nascent DNA. In cell lines, primary cells and xenograft mouse models, inhibition of the H3K27 histone methyltransferase EZH2 to decondense the H3K27me3-marked chromatin of AML cells enhanced chromatin accessibility and chemotherapy-induced DNA damage, apoptosis, and leukemia suppression.

Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

Background: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD).

Screening of Acute Traumatic Stress Disorder and Posttraumatic Stress Disorder in Pediatric Trauma Patients: A Pilot Study.

Background: Children who experience traumatic physical injuries are at risk of developing acute stress disorder and posttraumatic stress disorder (PTSD). Early identification and treatment of these high-risk children can lead to improved mental health outcomes in this population.

Objective: This study assesses the feasibility of a study protocol that compares 3 screening tools for identifying patients at a high risk of later development of acute stress disorder or PTSD among pediatric trauma patients.

Effects of hydro-ethanolic extract of leaves of Maesa lanceolata (Mursinaceae) on acetic acid-induced ulcerative colitis in rats.

Ulcerative colitis is a form of inflammatory bowel disease that is characterized by acute and chronic inflammation. The aim of this work was to evaluate the efficacy of hydroethanolic extract of Maesa lanceolata leaves on acetic acid-induced colitis in rats. Colitis was induced by rectal administration of 1 mL of acetic acid (4%) in 25 male rats except the normal control group which received distilled water after 18 h of fasting followed by Ketamine (50 mg/kg)/Valium (10 mg/kg) anesthesia.

COVID-19 in Children With Kidney Disease: A Report of 2 Cases.

The presentation of novel coronavirus disease 2019 (COVID-19) in children with kidney disease is largely unknown. We report on 2 children with kidney disease not receiving long-term immunosuppression who were hospitalized due to COVID-19. The first case is an infant with end-stage kidney disease secondary to bilateral cystic dysplastic kidneys and posterior urethral valves receiving peritoneal dialysis, with a history of prematurity previously requiring mechanical ventilation in the neonatal intensive care unit, who presented with fever, hypertension, and emesis.

Effect of pacemaker implantation after transcatheter aortic valve replacement on long- and mid-term mortality.

Background: Transcatheter aortic valve replacement (TAVR) has become quite common. Atrioventricular conduction defects remain a frequent complication resulting with permanent pacemaker (PPM) implantation. Past studies showed conflicting results regarding PPM effect on mortality.

Selective inhibition of Ph-positive ALL cell growth through kinase-dependent and -independent effects by CDK6-specific PROTACs.

Expression of the cell cycle regulatory gene CDK6 is required for Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) cell growth, whereas expression of the closely related CDK4 protein is dispensable. Moreover, CDK6 silencing is more effective than treatment with the dual CDK4/6 inhibitor palbociclib in suppressing Ph+ ALL in mice, suggesting that the growth-promoting effects of CDK6 are, in part, kinase-independent in Ph+ ALL. Accordingly, we developed CDK4/6-targeted proteolysis-targeting chimeras (PROTACs) that inhibit CDK6 enzymatic activity in vitro, promote the rapid and preferential degradation of CDK6 over CDK4 in Ph+ ALL cells, and markedly suppress S-phase cells concomitant with inhibition of CDK6-regulated phospho-RB and FOXM1 expression.

Gain-of-Function Mutant p53 R273H Interacts with Replicating DNA and PARP1 in Breast Cancer.

Over 80% of triple-negative breast cancers (TNBC) express mutant p53 (mtp53) and some contain oncogenic gain-of-function (GOF) p53. We previously reported that GOF mtp53 R273H upregulates the chromatin association of mini chromosome maintenance (MCM) proteins MCM2-7 and PARP and named this the mtp53-PARP-MCM axis. In this study, we dissected the function and association between mtp53 and PARP using a number of different cell lines, patient-derived xenografts (PDX), tissue microarrays (TMA), and The Cancer Genome Atlas (TCGA) database.

Epigenetic regulation affects gene amplification in Drosophila development.

In Drosophila melanogaster, in response to developmental transcription factors, and by repeated initiation of DNA replication of four chorion genes, ovarian follicle cells, form an onion skin-type structure at the replication origins. The DNA replication machinery is conserved from yeast to humans. Subunits of the origin recognition complex (ORC) is comprised of Orc1, Orc2, and Cdc6 genes.

A Proximity Ligation-Based Method to Detect RNA-DNA Association.

We recently developed a method for assessing RNA-DNA interactions using proximity ligation assays (PLA). This technique, termed the "RNA-DNA interaction assay" (RDIA), involves differentially labeling DNA and RNA with EdU and BrU, respectively. Once labeled, PLA is performed to assess if the labeled molecules are in close proximity.

The Relative Age Effect in under-18 basketball: Effects on performance according to playing position.

The Relative Age Effect (RAE) in sport is defined as the age difference in the same sport group. This chronological difference implies a different level of sport experience and performance due to developmental and maturational processes. The aim of the present study was to analyze the relative age effect in elite u-18 basketball according to playing positions.

Arrhythmic Events in Brugada Syndrome: A Nationwide Israeli Survey of the Clinical Characteristics, Treatment; and Long-Term Follow-up (ISRABRU-VF).

Background: Limited information exists about detailed clinical characteristics and management of the small subset of Brugada syndrome (BrS) patients who had an arrhythmic event (AE).

Objectives: To conduct the first nationwide survey focused on BrS patients with documented AE.

Methods: Israeli electrophysiology units participated if they had treated BrS patients who had cardiac arrest (CA) (lethal/aborted; group 1) or experienced appropriate therapy for tachyarrhythmias after prophylactic implantable cardioverter defibrillator (ICD) implantation (group 2).

Xenobiotic-induced activation of human aryl hydrocarbon receptor target genes in is mediated by the epigenetic chromatin modifiers.

Aryl hydrocarbon receptor (AHR) is the key transcription factor that controls animal development and various adaptive processes. The AHR's target genes are involved in biodegradation of endogenous and exogenous toxins, regulation of immune response, organogenesis, and neurogenesis. Ligand binding is important for the activation of the AHR signaling pathway.

Super-response to cardiac resynchronization therapy reduces appropriate implantable cardioverter defibrillator therapy.

Aims: To determine the frequency of implantable cardioverter defibrillator (ICD) therapy following cardiac resynchronization therapy (CRT-D) implantation in super and non-super responders and whether greater improvement in left ventricular (LV) function after CRT is associated with a reduced burden in ICD therapy.

Methods And Results: This is a two-centre, retrospective study between January 2002 and September 2011. Patients were classified as non-super responders and super-responders based on the post-CRT ejection fraction (EF) of < 50% and ≥50%, respectively.