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Folate is an essential micronutrient required for both cellular proliferation through de novo nucleotide synthesis and epigenetic regulation of gene expression through methylation. This dual requirement places a particular demand on folate availability during pregnancy when both rapid cell generation and programmed differentiation of maternal, extraembryonic, and embryonic/fetal tissues are required. Accordingly, prenatal neurodevelopment is particularly susceptible to folate deficiency, which can predispose to neural tube defects, or when effective transport into the brain is impaired, cerebral folate deficiency. Consequently, adequate folate consumption, in the form of folic acid (FA) fortification and supplement use, is widely recommended and has led to a substantial increase in the amount of FA intake during pregnancy in some populations. Here, we show that either maternal folate deficiency or FA excess in mice results in disruptions in folate metabolism of the offspring, suggesting diversion of the folate cycle from methylation to DNA synthesis. Paradoxically, either intervention causes comparable neurodevelopmental changes by delaying prenatal cerebral cortical neurogenesis in favor of late-born neurons. These cytoarchitectural and biochemical alterations are accompanied by behavioral abnormalities in FA test groups compared with controls. Our findings point to overlooked potential neurodevelopmental risks associated with excessively high levels of prenatal FA intake.

Folate is an essential micronutrient required for both cellular proliferation through de novo nucleotide synthesis and epigenetic regulation of gene expression through methylation. This dual requirement places a particular demand on folate availability during pregnancy when both rapid cell generation and programmed differentiation of maternal, extraembryonic, and embryonic/fetal tissues are required. Accordingly, prenatal neurodevelopment is particularly susceptible to folate deficiency, which can predispose to neural tube defects, or when effective transport into the brain is impaired, cerebral folate deficiency. Consequently, adequate folate consumption, in the form of folic acid (FA) fortification and supplement use, is widely recommended and has led to a substantial increase in the amount of FA intake during pregnancy in some populations. Here, we show that either maternal folate deficiency or FA excess in mice results in disruptions in folate metabolism of the offspring, suggesting diversion of the folate cycle from methylation to DNA synthesis. Paradoxically, either intervention causes comparable neurodevelopmental changes by delaying prenatal cerebral cortical neurogenesis in favor of late-born neurons. These cytoarchitectural and biochemical alterations are accompanied by behavioral abnormalities in FA test groups compared with controls. Our findings point to overlooked potential neurodevelopmental risks associated with excessively high levels of prenatal FA intake.

Neural crest cells (NCCs) comprise a transient progenitor cell population of neuroepithelial origin that contributes to a variety of cell types throughout vertebrate embryos including most mesenchymal cells of the cranial and facial structures. Consequently, abnormal NCC development underlies a variety of craniofacial defects including orofacial clefts, which constitute some of the most common birth defects. We previously reported the generation of manta ray (mray) mice that carry a loss-of-function allele of the gene encoding the preribosomal factor Pak1ip1. Here we describe cranioskeletal abnormalities in homozygous mray mutants that arise from a loss of NCCs after their specification. Our results show that the localized loss of cranial NCCs in the developing frontonasal prominences is caused by cell cycle arrest and cell death. In addition, and consistent with deficits in ribosome biosynthesis, homozygous mray mutants display decreased protein biosynthesis, further linking Pak1ip1 to a role in ribosome biogenesis.

The underpinnings of mild to moderate neurodevelopmental delay remain elusive, often leading to late diagnosis and interventions. Here, we present data on exome and genome sequencing as well as array analysis of 13 individuals that point to pathogenic, heterozygous, mostly de novo variants in WDFY3 (significant de novo enrichment P = 0.003) as a monogenic cause of mild and non-specific neurodevelopmental delay. Nine variants were protein-truncating and four missense. Overlapping symptoms included neurodevelopmental delay, intellectual disability, macrocephaly, and psychiatric disorders (autism spectrum disorders/attention deficit hyperactivity disorder). One proband presented with an opposing phenotype of microcephaly and the only missense-variant located in the PH-domain of WDFY3. Findings of this case are supported by previously published data, demonstrating that pathogenic PH-domain variants can lead to microcephaly via canonical Wnt-pathway upregulation. In a separate study, we reported that the autophagy scaffolding protein WDFY3 is required for cerebral cortical size regulation in mice, by controlling proper division of neural progenitors. Here, we show that proliferating cortical neural progenitors of human embryonic brains highly express WDFY3, further supporting a role for this molecule in the regulation of prenatal neurogenesis. We present data on Wnt-pathway dysregulation in Wdfy3-haploinsufficient mice, which display macrocephaly and deficits in motor coordination and associative learning, recapitulating the human phenotype. Consequently, we propose that in humans WDFY3 loss-of-function variants lead to macrocephaly via downregulation of the Wnt pathway. In summary, we present WDFY3 as a novel gene linked to mild to moderate neurodevelopmental delay and intellectual disability and conclude that variants putatively causing haploinsufficiency lead to macrocephaly, while an opposing pathomechanism due to variants in the PH-domain of WDFY3 leads to microcephaly.

Purpose: This study aimed to assess the validity and informational value of TikTok content about epicondylitis. The hypothesis tested herein was that TikTok video content would not provide adequate and valid information. Methods: The term "epicondylitis" was used as a keyword to comprehensively search for TikTok videos, and the first 100 videos that were retrieved were subsequently included for analysis. The duration, number of likes, number of shares and number of views were recorded for each video. Furthermore, the videos were categorized on the basis of their source (medical doctor, physiotherapist, or private user), type of information (physical therapy, anatomy, clinical examination, etiopathogenesis, patient experience, treatment, or other), video content (rehabilitation, education, or patient experience/testimony), and the presence of music or voice. Assessments of video content quality and reliability were conducted using the DISCERN tool, the Journal of the American Medical Association (JAMA) benchmark criteria, and the Global Quality Score (GQS). Results: A total of 100 videos were included in the analysis: 78 (78.0%) were published by physiotherapists, 18 were published by medical doctors (18.0%), and 4 were published by private users (4.0%). Most of the information pertained to physical therapy (75; 75.0%) and most of the content was about rehabilitation (75; 75.0%). The mean length of the videos was 42.51 ± 24.75 seconds; the mean number of views was 193,207.78 ± 1,300,853.86; and the mean number of comments, likes, and shares were 22.43 ± 62.54, 1578.52 ± 8333.11, and 149.87 ± 577.73, respectively. The mean DISCERN score, JAMA score, and GQS were 18.12 ± 5.73, 0.80 ± 0.53, and 1.30 ± 0.52, respectively. Videos posted by medical doctors/private users had higher scores (p < 0.05) than videos posted by physiotherapists. Videos that focused on education or patient experience had higher scores (p < 0.05) than videos based on rehabilitation. Conclusions: TikTok can be an unreliable source of information regarding epicondylitis treatment. It is common to find nonphysicians who share medical advice on the platform, with medical treatments demonstrating the weakest level of supporting evidence. Elbow surgeons should advise their patients that treatment recommendations from TikTok may not align with established guidelines. Level of Evidence: Level IV—Cross-sectional study. [ABSTRACT FROM AUTHOR]

Background: Open Bankart repair and Latarjet stabilization are two of surgical procedures used in the treatment of shoulder instability in contact athletes. The aim of this study is to evaluate the outcomes of bone block arthroscopic procedure, performed with xenograft, in combination with Bankart repair and selective subscapularis augmentation (ASA) for contact athletes with recurrent anterior shoulder instability., Methods: We retrospectively assessed contact athletes who underwent arthroscopic bone block with xenograft and Bankart repair with selective augmentation of subscapularis for recurrent anterior shoulder instability between January 2017 and December 2021. Shoulders with posterior instability or multidirectional instability were excluded. Recurrence, complications, return to sport, and functional scores (Rowe score, WOSI score, ASES score) were assessed. A CT scan at 2-year follow-up was performed to assess the status of Bone block integration, its displacement and restoration of glenoid surface., Results: 16 patients were included in the study with a mean age of 24. None of the patients treated with arthroscopic bone block and ASA presented new dislocation episodes. An increase in preoperative scores was observed at the last follow-up, in particular the ASES, Rowe, and WOSI scores increased from 69±7, 31±9 , 1235±46 respectively to 96.1±3.2, 94±6, 119±51. All athletes returned to sporting activity at or near the same level as pre-surgery. The glenoid bone surface increase from 83% to 116% at last follow-up., Conclusion: Bone block treatment with Xenograft combined with Bankart repair and ASA procedures has been shown to be effective in treating instability in contact athletes with significant glenoid deficit. All athletes returned to athletic activity at a level similar to the pre-intervention period., (Copyright © 2024. Published by Elsevier Inc.)

The management of residual elbow instability is challenging in both acute and chronic injuries. Among the available devices, the hinged external fixator provides an additional joint stabilization while allowing an early motion, but it is clumsy and associated to high rate of pin track complications. To address these issues, an internal joint stabilizer (IJS) has been recently developed. An easier recreation of the axis of rotation coupled to the reduced lever arm of the hinge is the root of the consistent and satisfactory results thus far observed. In addition, the device is more comfortable for the patients being an internal stabilizer. Nonetheless, a second surgery for the device removal is necessary, of which the timing is still not standardized. This current concepts paper describes literature regarding outcomes of the IJS focusing on the rate of maintained radiographic joint reduction, the resultant range of motion, and the associated complication profile., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The elbow is a joint extremely susceptible to stiffness, even after a trivial trauma. As for other joints, several factors can generate stiffness such as immobilisation, joint incongruity, heterotopic ossification, adhesions, or pain. Prolonged joint immobilisation, pursued to assure bony and ligamentous healing, represents the most acknowledged risk factor for joint stiffness. The elbow is a common site of nerve entrapment syndromes. The reasons are multifactorial, but peculiar elbow anatomy and biomechanics play a role. Passing from the arm into the forearm, the ulnar, median, and radial nerves run at the elbow in close rapport with the joint, fibrous arches and through narrow fibro-osseous tunnel. The elbow joint, in fact, has a large range of flexion which exposes nerves lying posterior to the axis of rotation to traction and those anterior to compression., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)