Tissue informative cell-free DNA methylation sites in amyotrophic lateral sclerosis.

Cell-free DNA (cfDNA) is increasingly recognized as a promising biomarker candidate for disease monitoring. However, its utility in neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS), remains underexplored. Existing biomarker discovery approaches are tailored to a specific disease context or are too expensive to be clinically practical. Here, we address these challenges through a new approach combining advances in molecular and computational technologies. First, we develop statistical tools to select tissue-informative DNA methylation sites relevant to a disease process of interest. We then employ a capture protocol to select these sites and perform targeted methylation sequencing. Multi-modal information about the DNA methylation patterns are then utilized in machine learning algorithms trained to predict disease status and disease progression. We applied our method to two independent cohorts of ALS patients and controls (n=192). Overall, we found that the targeted sites accurately predicted ALS status and replicated between cohorts. Additionally, we identified epigenetic features associated with ALS phenotypes, including disease severity. These findings highlight the potential of cfDNA as a non-invasive biomarker for ALS.

Vogt-Koyanagi-Harada disease after head trauma.

PURPOSE: To report two cases of Vogt-Koyanagi-Harada disease after closed head trauma. METHODS: Case report. RESULTS: Two patients, one male and one female, developed headache, dysacusis, vertigo, tinnitus, and hair hypersensitivity shortly after a closed head trauma and, 10 and 18 days later, a bilateral uveitis with papillitis and exudative retinal detachment in one and a bilateral mild uveitis with macular exudative detachment in the other. The ocular lesions resolved with intravenous high-dose steroid therapy, but recurred after reduction of the dosages, requiring further steroid therapy. The course of the disease in both patients, with the appearance of fundus depigmentation and pigment clumping, and the occurrence of a concomitant ocular and auditory relapse in one, were typical of Vogt-Koyanagi-Harada disease. CONCLUSIONS: Vogt-Koyanagi-Harada disease may appear after a closed head trauma suggesting that even an indirect trauma in melanocyte-containing tissue may induce an inflammatory response within the eye.

Emergency department discharge instructions and patient literacy: a problem of disparity.

This two-part study was designed to determine the reading level necessary to understand commonly used emergency department (ED) discharge instructions and the functioning reading level of adult patients treated in an urban hospital ED. In the first phase, 10 preprinted patient discharge instructions were analyzed using the Flesch Reading Ease Score. The average reading level required to comprehend these instructions was 9.8, with a range from the 8th to the 14th grade. In the second phase of the study, a reading exam, based on the Stanford Diagnostic Reading Test, was administered to 82 ED patients prospectively. The mean reading level was 9.8, with a median level of 10; approximately 45% of the ED patients would be unable to understand the preprinted discharge instructions. ED discharge instructions are frequently written at a level beyond the comprehension of a significant portion of the population.

In vitro activity of cefpodoxime proxetil (U-76,252; CS-807) against clinical isolates of Branhamella catarrhalis.

Cefpodoxime proxetil (U-76,252; CS-807) is a new esterified oral cephem antibiotic with a broad antibacterial spectrum. Since data regarding the activity of cefpodoxime against Branhamella catarrhalis are limited, we tested its activity against 200 B. catarrhalis isolates. The drug was highly active against beta-lactamase-negative and -positive isolates; 99% of all strains tested showed a cefpodoxime proxetil MIC of less than or equal to 2.0 micrograms/ml.