We report a case of severe symptomatic hypercalcemia that resolved after a short course of therapy of exclusively fluids and furosemide. An extensive workup for metabolic, neoplastic, and drug-induced causes did not provide a possible etiology of the hypercalcemia. After calcium level returned to baseline, the patient was discharged, only to return a week later with multiple embolic strokes of unknown source.
View Article and Find Full Text PDFAims: Endotoxemia commonly occurs in severe and fatal COVID-19, suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS-CoV-2. We previously demonstrated that the endogenous glucagon like peptide 1 (GLP-1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram-negative sepsis and modulated by type 2 diabetes (T2D). We aimed to determine the association of COVID-19 severity with endogenous GLP-1 activation upregulated by increased specific pro-inflammatory innate immune response in patients with and without T2D.
View Article and Find Full Text PDFThe inner ear is a complex structure responsible for hearing and balance, and organ pathology is associated with deafness and balance disorders. To evaluate the role of epigenomic dynamics, we performed whole genome bisulfite sequencing at key time points during the development and maturation of the mouse inner ear sensory epithelium (SE). Our single-nucleotide resolution maps revealed variations in both general characteristics and dynamics of DNA methylation over time.
View Article and Find Full Text PDFBackground: Hearing loss is a major cause of disability worldwide, impairing communication, health, and quality of life. Emerging methods of gene therapy aim to address this morbidity, which can be employed to fix a genetic problem causing hair cell dysfunction and to promote the proliferation of supporting cells in the cochlea and their transdifferentiation into hair cells. In order to extend the applicability of gene therapy, the scientific community is focusing on discovery of additional deafness genes, identifying new genetic variants associated with hearing loss, and revealing new factors that can be manipulated in a coordinated manner to improve hair cell regeneration.
View Article and Find Full Text PDFMammalian genomes encode multiple layers of regulation, including a class of RNA molecules known as long non-coding RNAs (lncRNAs). These are >200 nucleotides in length and similar to mRNAs, they are capped, polyadenylated, and spliced. In contrast to mRNAs, lncRNAs are less abundant and have higher tissue specificity, and have been linked to development, epigenetic processes, and disease.
View Article and Find Full Text PDFBackground: The quantitative relations between RNA and protein are fundamental to biology and are still not fully understood. Across taxa, it was demonstrated that the protein-to-mRNA ratio in steady state varies in a direction that lessens the change in protein levels as a result of changes in the transcript abundance. Evidence for this behavior in tissues is sparse.
View Article and Find Full Text PDF