ABSTRACT
Sinus bradycardia is defined as a heart rate of less than 60 beats per minute and can occur as an adaptive response but can also be pathologic. Sinus bradycardia can be a normal finding in children, individuals who exercise often, and as a physiologic response during sleep. Pathologic causes of sinus bradycardia include sinus node dysfunction, medications, acute myocardial infarction, heart failure, obstructive sleep apnea, exaggerated vagal activity, increased intracranial hypertension, infection, hypothyroidism, hypothermia, anorexia nervosa, and prolonged hypoxia. When pathologic, addressing the underlying cause will lead to an improvement in heart rate. Here, we present a case of sinus bradycardia in a 61-year-old female with hypothermia. Evaluation for common causes of bradycardia including cardiac evaluation was unremarkable. Treatment of hypothermia led to the resolution of bradycardia. The importance of the case is to help clinicians recognize hypothermia as a cause of bradycardia.
ABSTRACT
Proteasomes are the central proteolytic machines that are critical for breaking down most of the damaged and abnormal proteins in human cells. Although universally applicable drugs are not yet available, the stimulation of proteasomal activity is being analyzed as a proof-of-principle strategy to increase cellular resistance to a broad range of proteotoxic stressors. These approaches have included the stimulation of proteasomes through the overexpression of individual proteasome subunits, phosphorylation, or conformational changes induced by small molecules or peptides. In contrast to these approaches, we evaluated a transcription-driven increase in the total proteasome pool to enhance the proteolytic capacity of degenerating retinal neurons. We show that overexpression of nuclear factor erythroid-2-like 1 (Nfe2l1) transcription factor stimulated proteasome biogenesis and activity, improved the clearance of the ubiquitin-proteasomal reporter, and delayed photoreceptor neuron loss in a preclinical mouse model of human blindness caused by misfolded proteins. The findings highlight Nfe2l1 as an emerging therapeutic target to treat neurodegenerative diseases linked to protein misfolding.
