Congenital Myasthenic Syndrome associated with acetylcholine receptor deficiency: case report and review of the literature.

INTRODUCTION: Congenital Myasthenic Syndromes are a diverse group of conditions with a broad array of genetic underpinnings and phenotypic presentations. Acetylcholine receptor deficiency is one form that usually involves pathogenic variants in the Cholinergic Receptor Nicotinic Epsilon Subunit (CHRNE) gene encoding the ɛ-subunit of the acetylcholine receptor. METHODS: We report a case of a 4-year-old male with suspected Congenital Myasthenic Syndrome with Acetylcholine Receptor Deficiency who presented with ocular symptoms and generalized muscle weakness. We additionally summarize published findings regarding the genetic, phenotypic, and clinical considerations of Congenital Myasthenic Syndrome with Acetylcholine Receptor Deficiency. RESULTS: Exome sequencing revealed biallelic variants in CHRNE gene with a pathogenic frameshift variant and a variant of uncertain significance. After suboptimal response to pyridostigmine and albuterol, the patient experienced benefit with 3,4-DAP. The most commonly reported clinical characteristics in the literature are ptosis, muscle fatigability or weakness, and ophthalmoplegia. CONCLUSION: We present the case of a patient with biallelic variants in CHRNE gene including a variant of uncertain significance. Evaluation of variants of this gene, including the variant of uncertain significance identified in this case report, through further cases and studies may improve our understanding of Congenital Myasthenic Syndrome with Acetylcholine Receptor deficiency.

A National Survey Evaluating Burnout and Wellness During Radiology Residency.

RATIONALE AND OBJECTIVES: Burnout is a serious problem during medical residency and can contribute to poorer resident and patient health. A thorough understanding of factors associated with burnout can provide insight into supporting resident well-being. The purpose of this study is to assess the prevalence of burnout and ascertain its associated factors among radiology residents in the U.S. MATERIALS AND METHODS: This cross-sectional study involved sending an anonymous survey to radiology program directors, coordinators, and residents across the U.S. Data regarding demographics, burnout levels, and burnout-associated factors were collected in the month of August 2023. Multivariable linear regression models evaluated the association of demographic and burnout-associated variables with burnout scores in the dimensions of Emotional Exhaustion, Depersonalization, and Personal Accomplishment. Chi-square analyses with Bonferroni correction and Kruskal-Wallis analyses were used to assess associations between program types and burnout as well as between program type and program effectiveness in managing burnout. Resident suggestions on addressing burnout were qualitatively assessed. RESULTS: 147 radiology residents responded to the survey. Emotional Exhaustion was positively associated with seeking social support (p = .03) and negatively associated with perceived program effectiveness in addressing burnout (p < .001). Respondents who identified as male experienced greater Depersonalization (p = .02). Increased frequency of physical activity was associated with higher Personal Accomplishment scores (p = .04). The most common resident suggestions related to Work Burden, Program Support, and Protected Wellness Time. CONCLUSION: Radiology programs should consider designing interventions addressing burnout, such as enhancing avenues for feedback and tailoring resident training based on individual preferences for remote work. Understanding the unique challenges faced by radiology residents is essential to tackle burnout and improve wellness.

Considerations for Use of the MAUDE Database in Otolaryngology-Head & Neck Surgery Research.

The use of the US Food and Drug Administration's (FDA) Manufacturer and User Facility Device Experience (MAUDE) to analyze adverse events linked to medical devices has grown in recent years. MAUDE facilitates post-market surveillance, contributing to the assessment of device performance and the identification of potential safety concerns. The database is instrumental not only for mandatory reporters such as manufacturers and healthcare facilities but also offers a platform for voluntary submissions from clinicians and patients, thus widening the scope of data collection. While the database offers valuable data, there are important limitations that must be understood in order to encourage appropriate interpretation of findings. This commentary highlights the major advantages and disadvantages of the MAUDE database, as well as describes possible areas for improvement in adverse event reporting.

The amphibian (Xenopus laevis) colony-stimulating factor-1 and interleukin-34-derived macrophages possess disparate pathogen recognition capacities.

Pathogens such as the Frog Virus 3 (FV3) ranavirus are contributing to the worldwide amphibian declines. While amphibian macrophages (Mϕs) are central to the immune defenses against these viruses, the pathogen recognition capacities of disparate amphibian Mϕ subsets remain unexplored. In turn, Mϕ differentiation and functionality are interdependent on the colony-stimulating factor-1 receptor (CSF-1R), which is ligated by colony-stimulating factor-1 (CSF-1) and the unrelated interleukin-34 (IL-34) cytokines. Notably, the Xenopus laevis frog CSF-1- and IL-34-derived Mϕs are functionally distinct, and while the CSF-1-Mϕs are more susceptible to FV3, the IL-34-Mϕs are highly resistant to this pathogen. Here, we elucidate the pathogen recognition capacities of CSF-1- and IL-34-differentiated Mϕs by evaluating their baseline transcript levels of key pathogen pattern recognition receptors (PRRs). Compared to the frog CSF-1-Mϕs, their IL-34-Mϕs exhibited greater expression of PRR genes associated with viral recognition as well as PRR genes known for recognizing bacterial pathogen-associated molecular patterns (PAMPs). By contrast, the CSF-1-Mϕs displayed greater expression of toll-like receptors (TLRs) that are absent in humans. Moreover, although the two Mϕ types possessed similar expression of most downstream PRR signaling components, they exhibited distinct outcomes upon stimulation with hallmark PAMPs, as measured by their tumor necrosis factor-alpha and interferon-7 gene expression. Remarkably, stimulation with a TLR2/6 agonist conferred FV3 resistance to the otherwise susceptible CSF-1-Mϕs while treatment with a TLR9 agonist significantly ablated the IL-34-Mϕ resistance to FV3. These changes in Mϕ-FV3 susceptibility and resistance appeared to be linked to changes in their expression of key immune genes. Greater understanding of the amphibian macrophage pathogen-recognition capacities will lend to further insights into the pathogen-associated causes of the amphibian declines.