Cross-Comparison of Human iPSC Motor Neuron Models of Familial and Sporadic ALS Reveals Early and Convergent Transcriptomic Disease Signatures.

Induced pluripotent stem cell (iPSC)-derived neural cultures from amyotrophic lateral sclerosis (ALS) patients can model disease phenotypes. However, heterogeneity arising from genetic and experimental variability limits their utility, impacting reproducibility and the ability to track cellular origins of pathogenesis. Here, we present methodologies using single-cell RNA sequencing (scRNA-seq) analysis to address these limitations. By repeatedly differentiating and applying scRNA-seq to motor neurons (MNs) from healthy, familial ALS, sporadic ALS, and genome-edited iPSC lines across multiple patients, batches, and platforms, we account for genetic and experimental variability toward identifying unified and reproducible ALS signatures. Combining HOX and developmental gene expression with global clustering, we anatomically classified cells into rostrocaudal, progenitor, and postmitotic identities. By relaxing statistical thresholds, we discovered genes in iPSC-MNs that were concordantly dysregulated in postmortem MNs and yielded predictive ALS markers in other human and mouse models. Our approach thus revealed early, convergent, and MN-resolved signatures of ALS.

Gastrointestinal Prophylaxis in Sports Medicine.

CONTEXT: Because sports participation at all levels often requires international travel, coaches, athletic trainers, and team physicians must effectively protect athletes from gastrointestinal infections. Traveler's diarrhea is the most common travel-related illness and can significantly interfere with training and performance. EVIDENCE ACQUISITION: A review of relevant publications was completed using PubMed and Google Scholar. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 5 Results: Enterotoxigenic and enteroaggregative Escherichia coli are the most common bacterial causes of traveler's diarrhea. Traveler's diarrhea generally occurs within 4 days of arrival, and symptoms tend to resolve within 5 days of onset. There are several prophylactic agents that physicians can recommend to athletes, including antibiotics, bismuth subsalicylate, and probiotics; however, each has its own unique limitations. Decision-making should be based on the athlete's destination, length of stay, and intent of travel. CONCLUSION: Prophylaxis with antibiotics is highly effective; however, physicians should be hesitant to prescribe medication due to the side effects and risks for creating antibiotic-resistant bacterial strains. Antibiotics may be indicated for high-risk groups, such as those with a baseline disease or travelers who have little flexible time. Since most cases of traveler's diarrhea are caused by food and/or water contamination, all athletes should be educated on the appropriate food and water consumption safety measures prior to travel.