Cortical assembloids support the development of fast-spiking human PVALB+ cortical interneurons and uncover schizophrenia-associated defects.

Disruption of parvalbumin positive (PVALB+) cortical interneurons is implicated in the pathogenesis of schizophrenia. However, how these defects emerge during brain development remains poorly understood. The protracted maturation of these cells during postnatal life has made their derivation from human pluripotent stem cells (hPSCs) extremely difficult, precluding hPSC-based disease modeling of their role in neuropsychiatric disease.

Acute and chronic optical coherence tomography findings in partial optic nerve head avulsion.

We present a case of partial optic nerve head (ONH) avulsion in a 15-year-old boy evaluated with optical coherence tomography (OCT) from 2 weeks to 15 months after acute injury. Distinct findings on OCT in the acute setting correlated with the diagnosis and with additional testing, including fundus photography, Humphrey visual fields, and clinical examination. OCT findings became less pronounced in the chronic setting.

Brain MRI Lesions in Alexia Without Agraphia: A Case-Control Study.

Background: Alexia without agraphia (AWA) is an acquired reading disturbance associated with left posterior cerebral artery (PCA) infarction. Based on autopsy and neuroimaging, there are two explanations for its pathogenesis: a visual cortex-language cortex disconnection and a visual word-form agnosia. Our goal was to discover if more refined brain imaging in a case-control study would provide further imaging support for either of these hypotheses.

An Interdisciplinary Approach Toward Developing an Engaging and Clinically Relevant Medical Imaging Curriculum.

Rationale And Objectives: Competency in imaging is essential for physicians to diagnose and manage disease. Previously, the authors introduced radiology education in the anatomy lab. The present study transitioned the radiology education to the classroom with the primary goal of increasing engagement and clinical relevance.

A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins.

Target class-focused drug discovery has a strong track record in pharmaceutical research, yet public domain data indicate that many members of protein families remain unliganded. Here we present a systematic approach to scale up the discovery and characterization of small molecule ligands for the WD40 repeat (WDR) protein family. We developed a comprehensive suite of protocols for protein production, crystallography, and biophysical, biochemical, and cellular assays.

Clinical outcomes of nonsurgical root canal treatment using NeoSealer Flo and Endosequence BC Sealer: A retrospective analysis with short-term follow-up.

Objectives: Sealers are an important component in root canal obturation to provide the seal of the root canal system. In recent years, there has been an increase in the use of hydraulic silicate sealers, commonly referred to as bioceramic sealers, due to their many advantageous properties. NeoSealer Flo (NS; Avalon Biomed USA, Houston TX) is a recently introduced premixed bioceramic sealer.

Development of a bleeding arteriovenous fistula task trainer.

Background: As end-stage renal disease becomes more prevalent in the United States, the number of Americans with arteriovenous (AV) fistulas continues to increase. One of the most feared complications of AV fistulas is life-threatening hemorrhage, as patients can exsanguinate within minutes.

Objectives: As frontline healthcare workers, emergency medicine (EM) providers need to be able to provide rapid and effective treatment for this rare presentation.

Enrollment of underserved racial and ethnic populations in pediatric asthma clinical trials.

Background: The existing data on enrollment trends of historically underserved racial and ethnic children in clinical trials are limited.

Objective: We sought to evaluate documentation and representation of race and ethnicity in pediatric asthma clinical trials in the United States.

Methods: This is a cross-sectional study of United States-based interventional trials studying pediatric asthma that were completed between 2008 and 2022 and registered on ClinicalTrials.

Protocol for generating human cortical organoids enriched in outer radial glia by guided differentiation.

The generation of human pluripotent stem cell (hPSC)-derived brain organoids is continuously refined, enhancing their reproducibility and complexity. Here, we present a guided differentiation protocol for generating cortical forebrain organoids and cortico-pericyte (CP)assembloids composed of a robust outer radial glia (oRG) population and an expanded outer subventricular zone (oSVZ). We describe the steps to generate hPSC-derived cortical organoids (COs), cortical pericytes, and CP assembloids.

Generation of human cerebral organoids with a structured outer subventricular zone.

Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and the expansion of the neocortex. The in vitro generation of oRG is essential to investigate the underlying mechanisms of human neocortical development and expansion. By activating the STAT3 signaling pathway using leukemia inhibitory factor (LIF), which is not expressed in guided cortical organoids, we define a cortical organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ.

Living and post-mortem CT scans in the gross anatomy lab: A study investigating differences in first-year medical students' exam performance and perceptions.

Basic competency in radiological imaging is essential for physicians to identify and manage diseases. An optimal place in which to include imaging in the medical curriculum is during anatomy as students can correlate the 3D anatomy from their body donors with the 2D cross-sectional anatomy. The goal of this project was to enhance first-year medical students' knowledge of cross-sectional imaging in the gross anatomy lab and to investigate whether there are benefits to learning cross sectional imaging via scans from body donors versus living individuals.

Combined small-molecule treatment accelerates maturation of human pluripotent stem cell-derived neurons.

The maturation of human pluripotent stem cell (hPSC)-derived neurons mimics the protracted timing of human brain development, extending over months to years for reaching adult-like function. Prolonged in vitro maturation presents a major challenge to stem cell-based applications in modeling and treating neurological disease. Therefore, we designed a high-content imaging assay based on morphological and functional readouts in hPSC-derived cortical neurons which identified multiple compounds that drive neuronal maturation including inhibitors of lysine-specific demethylase 1 and disruptor of telomerase-like 1 and activators of calcium-dependent transcription.

Attaining Diagnostic Excellence: How the Structure and Function of a Rare Disease Service Contribute to Ending the Diagnostic Odyssey.

Patients with rare or otherwise undiagnosed disorders frequently find themselves on a diagnostic odyssey, the often-prolonged journey toward diagnosis that can be characterized by significant physical, emotional, and financial hardship, as well as by diagnostic errors and delays. The wider availability of clinical exome sequencing has helped end many diagnostic odysseys, though diagnostic success rates of around 35% for exome sequencing leave many patients undiagnosed. Diagnostic yields can be improved via the implementation of advanced genetic testing modalities, though both these modalities and exome sequencing perform significantly better when paired with high-quality phenotypic data.

Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care.

The prevalence, characteristics, and risk factors of external cervical resorption: a retrospective practice-based study.

Objectives: External cervical root resorption (ECR) is a poorly understood and aggressive form of resorption. The purpose of this study was to examine the prevalence, characteristics, and risk factors associated with the occurrence of ECR in patients seeking endodontic care from private practice settings.

Materials And Methods: Records of 343 patients with 390 teeth diagnosed with ECR were identified from 3 private endodontic practices from 2008 to 2022.

A retrospective study of initial root canal treatment failure in maxillary premolars via using cone-beam computed tomography.

Background: This case-series study examined canal morphology and common factors for endodontic failure in maxillary first and second premolars that were referred for retreatment owing to clinical symptoms or radiographic signs.

Methods: Records were retrospectively searched using Current Dental Terminology codes to identify maxillary first and second premolars with endodontic failure. Periapical and cone-beam computed tomographic images were examined to determine Vertucci classifications and suspected factors related to treatment failure.

The 'omics of obesity in B-cell acute lymphoblastic leukemia.

The obesity pandemic currently affects more than 70 million Americans and more than 650 million individuals worldwide. In addition to increasing susceptibility to pathogenic infections (eg, SARS-CoV-2), obesity promotes the development of many cancer subtypes and increases mortality rates in most cases. We and others have demonstrated that, in the context of B-cell acute lymphoblastic leukemia (B-ALL), adipocytes promote multidrug chemoresistance.

Managing a Deep Subgingival Cusp Fracture: Case Reports.

Cuspal fractures are relatively common. Fortunately for esthetics, when a cuspal fracture occurs in a maxillary premolar, it most commonly involves the palatal cusp. Fractures with a favorable prognosis may be approached with a minimally invasive treatment to successfully retain the natural tooth.