"Consider-the-Opposite" Debiasing to Improve Self-Assessment Accuracy in Anesthesiology Trainees: A Prospective Pretest-Posttest Study.

Accurate self-assessments enhance learning and patient care, yet resident physicians self-assess poorly. We therefore tested the effects of a consider-the-opposite (CTO) cognitive debiasing technique on self-assessment accuracy among anesthesiology residents. Trainees self-assessed their technical skills and communication/leadership abilities, then completed a CTO intervention before repeating self-assessments.

Molecular matching tools for allocation and immunosuppression optimization. Ready for primetime?

Purpose Of Review: Molecular matching continues to be an important topic in organ transplantation. Over the years, several studies - larger and smaller - supported correlations of molecular incompatibility loads and clinical outcomes. However, their practical utility for clinical decision making remains controversial and there is no consensus on the context in which they should be used.

Surgical management of skull base and spinal chordomas: A case series with comprehensive review of the literature.

Background: Chordomas are rare, slow growing, locally aggressive malignant bone tumors that arise from remnants of the embryonic notochord with variable presenting symptoms depending on tumor location.

Methods: All patients with craniospinal chordoma managed at our institution between 1982 and 2023 were retrospectively reviewed. Demographics, tumor characteristics, clinical course and treatment, and long-term neurological and survival outcomes were collected.

A Methodological Study on Microbial In Vivo Sampling Methods of Root Canal Microbiota for Next-Generation Gene Sequencing Analysis.

Introduction: The aim was to evaluate the suitability of paper points or endodontic nickel-titanium files to sample microorganisms for in vivo investigation of endodontic microbiota by 16S ribosomal DNA (rDNA) sequencing.

Methods: Forty-five patients presenting clinical and radiological signs of apical periodontitis were recruited for sampling, giving their written informed consent. Glide paths were assessed using C-Pilot Files and K-Files under electronic root canal length control under aseptic conditions.

The role of the oral microbiota in the causal effect of adjunctive antibiotics on clinical outcomes in stage III-IV periodontitis patients.

Background: Periodontitis, a prevalent chronic inflammatory disease, offers insights into the broader landscape of chronic inflammatory conditions. The progression and treatment outcomes of periodontitis are closely related to the oral microbiota's composition. Adjunctive systemic Amoxicillin 500 mg and Metronidazole 400 mg, often prescribed thrice daily for 7 days to enhance periodontal therapy's efficacy, have lasting effects on the oral microbiome.

Paternal HLA-Derived Epitopes and Live Birth in Secondary Recurrent Pregnancy Loss: New Insights From a Clinical Trial.

Recurrent pregnancy loss (RPL), defined as two or more pregnancy losses before the 24th week of gestation, affects 1%-3% of women worldwide. Approximately, 40% of RPL cases are secondary RPL (sRPL), where women have given birth before facing pregnancy losses. The underlying causes of RPL remain unclear, but immune-related factors may play a role.

iPSC-Derived LCHADD Retinal Pigment Epithelial Cells Are Susceptible to Lipid Peroxidation and Rescued by Transfection of a Wildtype AAV-HADHA Vector.

Purpose: Progressive choroid and retinal pigment epithelial (RPE) degeneration causing vision loss is a unique characteristic of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), a fatty acid oxidation disorder caused by a common c.1528G>C pathogenic variant in HADHA, the α subunit of the mitochondrial trifunctional protein (TFP). We established and characterized an induced pluripotent stem cell (iPSC)-derived RPE cell model from cultured skin fibroblasts of patients with LCHADD and tested whether addition of wildtype (WT) HAHDA could rescue the phenotypes identified in LCHADD-RPE.

Genitourinary cancer and family: The reverberating psychological and cardiovascular effects of a genitourinary cancer diagnosis on first-degree relatives and spouses.

Background: The psychological and cardiovascular health impacts on family members of patients who have been diagnosed with cancer have not been well characterized. The purpose of this study is to determine whether a family member's cancer diagnosis influences the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients affected by cancer.

Methods: This retrospective cohort analysis evaluated the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients diagnosed with a genitourinary cancer between 1990 and 2015 compared to relatives of those not diagnosed with a genitourinary cancer.

Sensitivity of transferrin isoform analysis for PMM2-CDG.

Transferrin isoform analysis is an established laboratory test for congenital disorders of glycosylation (CDG). Despite its long history of clinical use, little has been published about its empirical sensitivity for specific conditions. We conducted a retrospective analysis of ten years of testing data and report our experience with transferrin testing for type I profiles and its sensitivity for the most common congenital disorder of glycosylation, PMM2-CDG.

Development of a Multiplexed Sphingolipids Method for Diagnosis of Inborn Errors of Ceramide Metabolism.

Background: Sphingolipids play a crucial role in cellular functions and are essential components of cell membranes, signaling molecules, and lipid metabolism. In particular, ceramide is a key intermediate in sphingolipid metabolism and defects in ceramide metabolism can lead to various inborn errors of metabolism, making ceramides important targets for clinical screening and diagnosis. Detecting altered concentration patterns of sphingolipids is desirable for distinguishing related inborn errors of metabolism for diagnosis and treatment monitoring.

A multiplexed targeted method for profiling of serum gangliosides and glycosphingolipids: application to GM2-gangliosidosis.

The analysis of gangliosides and glycosphingolipids is crucial for understanding cellular membrane structure and function as well as to accurately diagnose certain inborn errors of metabolism. GM2-gangliosidosis represents a rare and fatal group of lysosomal storage disorders characterized by accumulation of GM2 gangliosides in various tissues and organs. These disorders arise due to deficiency or functional impairment of the β-hexosaminidase A or B enzymes, which are responsible for degradation of GM2 ganglioside.

Genotype and Phenotype Correlation of the TPMT∗8 Allele in Thiopurine Metabolism.

Thiopurine 6-mercaptopurine (6-MP) is metabolized by thiopurine methyl transferase (TPMT). TPMT genetic variation results in some individuals having reduced or absent TPMT enzyme activity. If these individuals take a full thiopurine dose, life-threatening adverse events can occur.

Pre-analytic decrease of phenylalanine in plasma of patients with phenylketonuria treated with pegvaliase.

Treatment of phenylketonuria (PKU) has evolved since the initial introduction of a phenylalanine (Phe) restricted diet. The most recent option for adults affected with PKU is treatment with an alternate enzyme, phenylalanine ammonia lyase (PAL), that metabolizes excess Phe. Proper management of all patients with PKU relies on accurate measurement of Phe levels in blood, to comply with guidance intended to minimize the neurological symptoms.

PIRCHE-II Risk and Acceptable Mismatch Profile Analysis in Solid Organ Transplantation.

To optimize outcomes in solid organ transplantation, the HLA genes are regularly compared and matched between the donor and recipient. However, in many cases a transplant cannot be fully matched, due to widespread variation across populations and the hyperpolymorphism of HLA alleles. Mismatches of the HLA molecules in transplanted tissue can be recognized by immune cells of the recipient, leading to immune response and possibly organ rejection.

Intraventricular Pilocytic Astrocytoma in Adults: A 25-year Single-Center Case Series and Systematic Review of the Literature.

Background: Pilocytic astrocytomas (PA) are the most common gliomas in children/adolescents but are less common and poorly studied in adults. Here, we describe the clinical presentation, surgical management, and outcomes of surgically treated adult patients with intraventricular (IV) PA and review the literature.

Methods: Consecutive adult patients treated for IV brain tumors at a tertiary academic center over 25 years (1997-2023) were identified.

SLC6A8 creatine transporter deficiency can be detected by plasma creatine and creatinine concentrations.

Creatine transporter deficiency has been described with normal or uninformative levels of creatine and creatinine in plasma, while urine has been the preferred specimen type for biochemical diagnosis. We report a cohort of untreated patients with creatine transporter deficiency and abnormal plasma creatine panel results, characterized mainly by markedly decreased plasma creatinine. We conclude that plasma should be considered a viable specimen type for the biochemical diagnosis of this disorder, and abnormal results should be followed up with further confirmatory testing.

Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair.

Homology Directed Repair (HDR) enables precise genome editing, but the implementation of HDR-based therapies is hindered by limited efficiency in comparison to methods that exploit alternative DNA repair routes, such as Non-Homologous End Joining (NHEJ). In this study, we develop a functional, pooled screening platform to identify protein-based reagents that improve HDR in human hematopoietic stem and progenitor cells (HSPCs). We leverage this screening platform to explore sequence diversity at the binding interface of the NHEJ inhibitor i53 and its target, 53BP1, identifying optimized variants that enable new intermolecular bonds and robustly increase HDR.

PIRCHE application major versions 3 and 4 lead to equivalent T cell epitope mismatch scores in solid organ and stem cell transplantation modules.

PIRCHE scores in organ and stem cell transplantation have been shown to correlate with increased risk of donor-specific HLA antibodies and graft-versus-host disease, respectively. With advancements of the PIRCHE application server, it is critical to compare the predicted scores with previous versions. This manuscript compares the newly introduced PIRCHE version 4.

Newborn Screening for Krabbe Disease: Status Quo and Recommendations for Improvements.

Krabbe disease (KD) is part of newborn screening (NBS) in 11 states with at least one additional state preparing to screen. In July 2021, KD was re-nominated for addition to the federal Recommended Uniform Screening Panel (RUSP) in the USA with a two-tiered strategy based on psychosine (PSY) as the determinant if an NBS result is positive or negative after a first-tier test revealed decreased galactocerebrosidase activity. Nine states currently screening for KD include PSY analysis in their screening strategy.

Repeated local ellipsoid protrusion supplements HLA surface characterization.

Allorecognition of donor HLA is a major risk factor for long-term kidney graft survival. Although several molecular matching algorithms have been proposed that compare physiochemical and structural features of the donors' and recipients' HLA proteins in order to predict their compatibility, the exact underlying mechanisms are still not fully understood. We hypothesized that the ElliPro approach of single ellipsoid fitting and protrusion ranking lacks sensitivity for the characteristic shape of HLA molecules and developed a prediction pipeline named Snowball that is fitting smaller ellipsoids iteratively to substructures.

Iron(II) Complexes of P -Chain Ligands: Structural Diversity.

Iron(II) complexes containing ligands with a R P-P-PR unit were synthesized by metathesis reactions. With R=tBu, a mixture of two isomers is formed; in one of them, the terminal phosphorus binds to the Fe center (ylidic structure), while in the other one, the central P atom is linked to Fe. Starting from differently functionalized parent triphosphanes and corresponding functionalized Fe complexes, the ratio of isomers does not change.