Designing structured postgraduate training programs using agile methods.

Postgraduate medical education (PGME) is an essential part of medical education and increasingly shifts into focus of educational stakeholders. Structured postgraduate medical training programs are required in the U.S.

Noncanonical assembly, neddylation and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex.

Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, 'cullin-RING' and 'RBR', are individually found in several hundred human E3 ligases, and collaborate with E2 enzymes to catalyze ubiquitylation. However, the vertebrate-specific CUL9 complex with RBX1 (also called ROC1), of interest due to its tumor suppressive interaction with TP53, uniquely encompasses both cullin-RING and RBR domains.

Structure of CRL7 reveals coupling with CUL1-RBX1/ROC1 for multi-cullin-RING E3-catalyzed ubiquitin ligation.

Most cullin-RING ubiquitin ligases (CRLs) form homologous assemblies between a neddylated cullin-RING catalytic module and a variable substrate-binding receptor (for example, an F-box protein). However, the vertebrate-specific CRL7 is of interest because it eludes existing models, yet its constituent cullin CUL7 and F-box protein FBXW8 are essential for development, and CUL7 mutations cause 3M syndrome. In this study, cryo-EM and biochemical analyses reveal the CRL7 assembly.

Heterogeneous Recommendations for School Attendance in Children With Chronic Kidney Diseases During the COVID-19 Pandemic in Europe.

After worldwide closures due to the COVID-19 pandemic, schools have reopened in most European countries in late 2020. Consequently, for children with chronic diseases the risks of COVID-19 have to be weighed against the long-time risks of missing school. To evaluate the impact of chronic diseases on school attendance for children in Europe during the COVID-19 pandemic we conducted a survey among members of the European Society for Pediatric Nephrology (ESPN) between September and November 2020.

Cognitive and behavioral risk factors for low quality of life in survivors of childhood acute lymphoblastic leukemia.

Background: With high survival rates for pediatric acute lymphoblastic leukemia (ALL), long-term quality of life is a prominent consideration in treatment. We concurrently evaluated cognition, behavior, and quality of life in child and adolescent ALL survivors and determined associations between them.

Methods: The sample included 83 controls (mean age: 12.

Divergent architecture of the heterotrimeric NatC complex explains N-terminal acetylation of cognate substrates.

The heterotrimeric NatC complex, comprising the catalytic Naa30 and the two auxiliary subunits Naa35 and Naa38, co-translationally acetylates the N-termini of numerous eukaryotic target proteins. Despite its unique subunit composition, its essential role for many aspects of cellular function and its suggested involvement in disease, structure and mechanism of NatC have remained unknown. Here, we present the crystal structure of the Saccharomyces cerevisiae NatC complex, which exhibits a strikingly different architecture compared to previously described N-terminal acetyltransferase (NAT) complexes.

Quantitative MRI outcomes in child and adolescent leukemia survivors: Evidence for global alterations in gray and white matter.

Introduction: Cure rates for pediatric acute lymphoblastic leukemia (ALL) have reached an all-time high (>90%); however, neurocognitive difficulties continue to affect quality of life in at least a subset of survivors. There are relatively few quantitative neuroimaging studies in child and adolescent ALL survivors treated with chemotherapy only. Use of different outcome measures or limited sample sizes restrict our ability to make inferences about patterns of brain development following chemotherapy treatment.

Neutrophil Extracellular Traps Contain Selected Antigens of Anti-Neutrophil Cytoplasmic Antibodies.

Neutrophil extracellular traps (NETs) are chromatin filaments decorated with enzymes from neutrophil cytoplasmic granules. Anti-neutrophil cytoplasmic antibodies (ANCAs) bind to enzymes from neutrophil cytoplasmic granules and are biomarkers for the diagnosis of systemic vasculitides. ANCA diagnostics are based on indirect immunofluorescence (IIF) of ethanol-fixed neutrophils.

Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes.

Introduction: Despite the success of epilepsy surgery, recent reports suggest a decline in surgical numbers. We tested these trends in our cohort to elucidate potential reasons.

Patients And Methods: Presurgical, surgical and postsurgical data of all patients undergoing presurgical evaluation in between 1990 and 2013 were retrospectively analysed.

Ambulatory Seizure Monitoring: From Concept to Prototype Device.

Background: The brain, made up of billions of neurons and synapses, is the marvelous core of human thought, action and memory. However, if neuronal activity manifests into abnormal electrical activity across the brain, neural behavior may exhibit synchronous neural firings known as seizures. If unprovoked seizures occur repeatedly, a patient may be diagnosed with epilepsy.

Circulating adipocyte fatty acid binding protein is increased in chronic and acute renal dysfunction.

Background And Aims: The adipokine adipocyte fatty acid binding protein (AFABP) is positively associated with the development of the metabolic syndrome, diabetes mellitus, and cardiovascular disease. We hypothesized that AFABP also increases with deteriorating renal function.

Methods And Results: Serum AFABP levels were quantified by enzyme linked immunosorbent assay in 532 patients with chronic kidney disease (CKD) covering the whole spectrum of estimated glomerular filtration rate (eGFR) categories from G1 to G5 (study population 1).

Serum levels of irisin in gestational diabetes mellitus during pregnancy and after delivery.

Objective: Irisin has recently been introduced as a novel an exercise-inducible myokine which improves glucose metabolism in mice. However, regulation of circulating irisin in gestational diabetes mellitus (GDM) and in the peripartal period has not been assessed so far.

Methods: Circulating irisin was quantified in 74 GDM patients and in 74 healthy, pregnant, gestational age-matched controls.

Hippocampal lateralization and memory in children and adults.

The neural organization of cognitive processes, particularly hemispheric lateralization, changes throughout childhood and adolescence. Differences in the neural basis of relational memory between children and adults are not well characterized. In this study we used magnetoencephalography to observe the lateralization differences of hippocampal activation in children and adults during performance of a relational memory task, transverse patterning (TP).

Binary diffusion coefficients for mixtures of ionic liquids [EMIM][N(CN)2], [EMIM][NTf2], and [HMIM][NTf2] with acetone and ethanol by dynamic light scattering (DLS).

Mutual diffusivities for binary mixtures of the ionic liquids (ILs) [EMIM][N(CN)2] (1-ethyl-3-methylimidazolium dicyanimide), [EMIM][NTf2] (1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide), and [HMIM][NTf2] (1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) with acetone and ethanol were studied in dependence on composition in the temperature range from 283.15 to 323.15 K, applying dynamic light scattering (DLS).