Recognizing differentiating clinical signs of CLN3 disease (Batten disease) at presentation

Purpose To help differentiate CLN3 (Batten) disease, a devastating childhood metabolic disorder, from the similarly presenting early-onset Stargardt disease (STGD1). Early clinical identification of children with CLN3 disease is essential for adequate referral, counselling and rehabilitation. Methods Medical chart review of 38 children who were referred to a specialized ophthalmological centre because of rapid vision loss. The patients were subsequently diagnosed with either CLN3 disease (18 patients) or early-onset STGD1 (20 patients). Results Both children who were later diagnosed with CLN3 disease, as children who were later diagnosed with early-onset STGD1, initially presented with visual acuity (VA) loss due to macular dystrophy at 5-10 years of age. VA in CLN3 disease decreased significantly faster than in STGD1 (p = 0.01). Colour vision was often already severely affected in CLN3 disease while unaffected or only mildly affected in STGD1. Optic disc pallor on fundoscopy and an abnormal nerve fibre layer on optical coherence tomography were common in CLN3 disease compared to generally unaffected in STGD1. In CLN3 disease, dark-adapted (DA) full-field electroretinogram (ERG) responses were either absent or electronegative. In early-onset STGD1, DA ERG responses were generally unaffected. None of the STGD1 patients had an electronegative ERG. Conclusion Already upon presentation at the ophthalmologist, the retina in CLN3 disease is more extensively and more severely affected compared to the retina in early-onset STGD1. This results in more rapid VA loss, severe colour vision abnormalities and abnormal DA ERG responses as the main differentiating early clinical features of CLN3 disease

The Perplexing Problem of Persistently PCR-Positive Personnel

Early in the coronavirus disease 2019 (COVID-19) pandemic, the Centers for Disease Control and Prevention (CDC) published return-to-work criteria for healthcare personnel who had recovered from severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection. These criteria were most recently updated on April 3, 2020.1 The CDC has endorsed 2 different approaches to allow staff to return to work: a symptom or time-based strategy and a test-based strategy. Many institutions initially adopted the test-based strategy, in part because CDC initially recommended it as the preferred option (but no longer does so) and, in part, because it seemed the more definitive or conservative of the 2 CDC options

miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients

PURPOSE: The proper validation of prognostic biomarkers is an important clinical issue in breast cancer research. MicroRNAs (miRNAs) have emerged as a new class of promising breast cancer biomarkers. In the present work, we developed an integrated online bioinformatic tool to validate the prognostic relevance of miRNAs in breast cancer. METHODS: A database was set up by searching the GEO, EGA, TCGA, and PubMed repositories to identify datasets with published miRNA expression and clinical data. Kaplan-Meier survival analysis was performed to validate the prognostic value of a set of 41 previously published survival-associated miRNAs. RESULTS: All together 2178 samples from four independent datasets were integrated into the system including the expression of 1052 distinct human miRNAs. In addition, the web-tool allows for the selection of patients, which can be filtered by receptors status, lymph node involvement, histological grade, and treatments. The complete analysis tool can be accessed online at: www.kmplot.com/mirpower . We used this tool to analyze a large number of deregulated miRNAs associated with breast cancer features and outcome, and confirmed the prognostic value of 26 miRNAs. A significant correlation in three out of four datasets was validated only for miR-29c and miR-101. CONCLUSIONS: In summary, we established an integrated platform capable to mine all available miRNA data to perform a survival analysis for the identification and validation of prognostic miRNA markers in breast cancer

The structure of the tetrasialoganglioside from human brain

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle- age onset. In nine families, we identified heterozygous C- terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias