Cross-species comparison reveals that Hmga1 reduces H3K27me3 levels to promote cardiomyocyte proliferation and cardiac regeneration.

In contrast to adult mammalian hearts, the adult zebrafish heart efficiently replaces cardiomyocytes lost after injury. Here we reveal shared and species-specific injury response pathways and a correlation between Hmga1, an architectural non-histone protein, and regenerative capacity, as Hmga1 is required and sufficient to induce cardiomyocyte proliferation and required for heart regeneration. In addition, Hmga1 was shown to reactivate developmentally silenced genes, likely through modulation of H3K27me3 levels, poising them for a pro-regenerative gene program.

An hiPSC-CM approach for electrophysiological phenotyping of a patient-specific case of short-coupled TdP.

Introduction: A healthy young woman, age 26 without prior cardiac complications, experienced an out-of-hospital cardiac arrest caused by ventricular fibrillation (VF), which coincided with a fever. Comprehensive diagnostics including echo, CMR, exercise testing, and genetic sequencing, did not identify any potential cause. This led to the diagnosis of idiopathic VF and installment of an implantable cardioverter defibrillator, which six months later appropriately intervened another VF episode under conditions comparable to the first event.

Urinary beta-2 microglobulin increases whereas TIMP-2 and IGFBP7 decline after unilateral nephrectomy in healthy kidney donors.

Early kidney injury may be detected by urinary markers, such as beta-2 microglobulin (B2M), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), kidney injury molecule-1 (KIM-1) and/or neutrophil gelatinase-associated lipocalin (NGAL). Of these biomarkers information on pathophysiology and reference ranges in both healthy and diseased populations are scarce. Differences in urinary levels of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL were compared 24 h before and after nephrectomy in 38 living kidney donors from the REnal Protection Against Ischaemia-Reperfusion in transplantation study.

Incidence rate of venous thrombosis in women switching combined oral contraceptives: a cohort study.

Background: The incidence rate of venous thrombosis (VT) in women switching combined oral contraceptives (COCs) is unknown.

Objectives: We hypothesize that women switching COCs may have a similar increased incidence rate of VT as women who start COCs. Switching means starting with a new COC, which may biologically approximate starting.

The safety of a low-protein diet in older adults with advanced chronic kidney disease.

Background: A low-protein diet (LPD) is recommended to patients with advanced chronic kidney disease (CKD), whereas geriatric guidelines recommend a higher amount of protein. The aim of this study was to evaluate the safety of LPD treatment in older adults with advanced CKD.

Methods: The EQUAL study is a prospective, observational study including patients ≥65 years of age with an incident estimated glomerular filtration rate <20 ml/min/1.

The impact of gender on the risk of cardiovascular events in older adults with advanced chronic kidney disease.

Background: Patients with chronic kidney disease (CKD) are at a higher risk of major adverse cardiovascular events (MACE) compared with the general population, but gender differences in this risk, especially in older adults, are not fully known. We aim to identify gender differences in the risk of MACE in older European CKD patients, and explore factors that may explain these differences.

Methods: The European Quality study (EQUAL) is a prospective study on stage 4-5 CKD patients, ≥65 years old, not on dialysis, from Germany, Italy, the Netherlands, Poland, Sweden and the UK.

Cardiomyocyte proliferation is suppressed by ARID1A-mediated YAP inhibition during cardiac maturation.

The inability of adult human cardiomyocytes to proliferate is an obstacle to efficient cardiac regeneration after injury. Understanding the mechanisms that drive postnatal cardiomyocytes to switch to a non-regenerative state is therefore of great significance. Here we show that Arid1a, a subunit of the switching defective/sucrose non-fermenting (SWI/SNF) chromatin remodeling complex, suppresses postnatal cardiomyocyte proliferation while enhancing maturation.

Urinary Kidney Injury Biomarkers Are Associated with Ischemia-Reperfusion Injury Severity in Kidney Allograft Recipients.

Background: We explored the potential of emerging and conventional urinary kidney injury biomarkers in recipients of living donor (LD) or donation after circulatory death (DCD) kidney transplantation, patients with chronic kidney disease (CKD), and individuals from the general population.

Methods: Urine samples from kidney allograft recipients with mild (LD; n = 199) or severe (DCD; n = 71) ischemia-reperfusion injury (IRI) were analyzed for neutrophil gelatinase-associated lipocalin (NGAL), insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinases 2 (TIMP2), kidney injury molecule-1 (KIM-1), chemokine C-X-C motif (CXCL9), solute carrier family 22 member 2 (SLC22A2), nephrin, and uromodulin (UMOD) by quantitative multiplex LC-MS/MS analysis. The fold-change in biomarker levels was determined in mild and severe IRI and in patients with CKD stage 1-2 (n = 127) or stage ≥3 (n = 132) in comparison to the general population (n = 1438).

Association between CKD-MBD and mortality in older patients with advanced CKD-results from the EQUAL study.

Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a common complication of CKD; it is associated with higher mortality in dialysis patients, while its impact in non-dialysis patients remains mostly unknown. We investigated the associations between parathyroid hormone (PTH), phosphate and calcium (and their interactions), and all-cause, cardiovascular (CV) and non-CV mortality in older non-dialysis patients with advanced CKD.

Methods: We used data from the European Quality study, which includes patients aged ≥65 years with estimated glomerular filtration rate ≤20 mL/min/1.

Gene editing innovations and their applications in cardiomyopathy research.

Cardiomyopathies are among the major triggers of heart failure, but their clinical and genetic complexity have hampered our understanding of these disorders and delayed the development of effective treatments. Alongside the recent identification of multiple cardiomyopathy-associated genetic variants, advances in genome editing are providing new opportunities for cardiac disease modeling and therapeutic intervention, both in vitro and in vivo. Two recent innovations in this field, prime and base editors, have improved editing precision and efficiency, and are opening up new possibilities for gene editing of postmitotic tissues, such as the heart.

Clinical and patient-reported trajectories at end-of-life in older patients with advanced CKD.

Background: We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with advanced chronic kidney disease (CKD).

Methods: The EQUAL study is a European observational prospective cohort study with an incident eGFR <20 ml/min per 1.73 m2 and ≥65 years of age.

Serum Potassium and Risk of Death or Kidney Replacement Therapy in Older People With CKD Stages 4-5: Eight-Year Follow-up.

Rationale & Objective: Hypokalemia may accelerate kidney function decline. Both hypo- and hyperkalemia can cause sudden cardiac death. However, little is known about the relationship between serum potassium and death or the occurrence of kidney failure requiring replacement therapy (KRT).

[Cardiomyopathy due to a mutation in the phospholamban gene: a high-impact genetic abnormality].

A mutation in the Phospholamban gene where the Arginine at position 14 (PLN-R14Del) is missing is causing a severe cardiomyopathy often leading to cardiac transplantation in the Netherlands. We estimated that approximately 25% of all transplanted patients carry this mutation. The origin is dated somewhere around the year 1300 in the north of country.

Pro-Arrhythmic Potential of Accumulated Uremic Toxins Is Mediated via Vulnerability of Action Potential Repolarization.

Chronic kidney disease (CKD) is represented by a diminished filtration capacity of the kidneys. End-stage renal disease patients need dialysis treatment to remove waste and toxins from the circulation. However, endogenously produced uremic toxins (UTs) cannot always be filtered during dialysis.

Desmosomal protein degradation as an underlying cause of arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited progressive cardiac disease. Many patients with ACM harbor mutations in desmosomal genes, predominantly in plakophilin-2 (). Although the genetic basis of ACM is well characterized, the underlying disease-driving mechanisms remain unresolved.

PITX2 induction leads to impaired cardiomyocyte function in arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited progressive disease characterized by electrophysiological and structural remodeling of the ventricles. However, the disease-causing molecular pathways, as a consequence of desmosomal mutations, are poorly understood. Here, we identified a novel missense mutation within desmoplakin in a patient clinically diagnosed with ACM.

Experimentally testing mate preference in an avian system with unidirectional bill color introgression.

Mating behavior can play a key role in speciation by inhibiting or facilitating gene flow between closely related taxa. Hybrid zones facilitate a direct examination of mating behavior and the traits involved in establishing species barriers. The long-tailed finch () has two hybridizing subspecies that differ in bill color (red and yellow), and the yellow bill phenotype appears to have introgressed ~350 km eastward following secondary contact.

Therapeutic efficacy of AAV-mediated restoration of PKP2 in arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy is a severe cardiac disorder characterized by lethal arrhythmias and sudden cardiac death, with currently no effective treatment. Plakophilin 2 () is the most frequently affected gene. Here we show that adeno-associated virus (AAV)-mediated delivery of PKP2 in induced pluripotent stem cell-derived cardiomyocytes restored not only cardiac PKP2 levels but also the levels of other junctional proteins, found to be decreased in response to the mutation.

Effect of residual kidney function and dialysis adequacy on chronic pruritus in dialysis patients.

Background: Chronic kidney disease-associated pruritus (CKD-aP) is common in dialysis patients, and is associated with lower quality of life and increased risk of death. We investigated the association between residual estimated glomerular filtration rate (eGFR), dialysis adequacy or serum phosphate level and CKD-aP in incident dialysis patients.

Methods: A total of 1256 incident hemodialysis (HD) and 670 peritoneal dialysis (PD) patients (>18 years) from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) study were included (1997-2007) and followed until death, transplantation or a maximum of 10 years.

Symptom Burden before and after Dialysis Initiation in Older Patients.

Background And Objectives: For older patients with kidney failure, lowering symptom burden may be more important than prolonging life. Dialysis initiation may affect individual kidney failure-related symptoms differently, but the change in symptoms before and after start of dialysis has not been studied. Therefore, we investigated the course of total and individual symptom number and burden before and after starting dialysis in older patients.

Thymosin β4 and prothymosin α promote cardiac regeneration post-ischaemic injury in mice.

Aims: The adult mammalian heart is a post-mitotic organ. Even in response to necrotic injuries, where regeneration would be essential to reinstate cardiac structure and function, only a minor percentage of cardiomyocytes undergo cytokinesis. The gene programme that promotes cell division within this population of cardiomyocytes is not fully understood.