Myocardial Infarction and Cardiac Arrest in a Patient With Severe Undiagnosed Hypothyroidism During Bronchoscopy.

Thyroid hormones have an integral role in cardiac homeostasis, and hypothyroidism may be associated with impaired myocardial contractility, altered endothelial function, and blunted response to catecholamines. Herein, the case of a patient with undiagnosed severe hypothyroidism, who developed an acute myocardial infarction and cardiac arrest during sedation for bronchoscopy, is described. He required prolonged resuscitation, which included coronary catheterization and placement of an intra-aortic balloon pump. The resuscitation was noteworthy for blunted physiologic responses to large doses of epinephrine; in particular, persistent bradycardia without evidence of conduction abnormalities. On admission to the intensive care unit, he was hypothermic (31.4°C), bradycardic, and hypotensive. Laboratory investigations revealed profound hypothyroidism, and thyroid hormone replacement was initiated. Within hours of initiation of thyroid hormone replacement, the need for vasopressor support was reduced. He had a complete recovery and was discharged home neurologically intact. The authors of the present report believe that this favorable neurologic outcome could be attributed to efficient resuscitation, prompt coronary revascularization, and profound hypothermia likely related to a hypothyroidism-associated hypometabolic state.

Coinfection of Aspergillus and Cryptococcus in Immunocompromised Host: A Case Report and Review of Literature.

Management of infections in the immunocompromised patient requires unique considerations that are not typically seen in the immunocompetent. Immunocompromised hosts require a broad set of differential diagnoses when presenting with febrile illness involving a wide variety of microbiology. Moreover, fungal infections are common, and cotreatment of fungal and bacterial infections occurs with regularity. Fungal coinfection, however, is rare. Here, we describe a patient with Aspergillus and recurrent Cryptococcus neoformans coinfection following completion of treatment for pulmonary cryptococcosis.

Optimized light-inducible transcription in mammalian cells using Flavin Kelch-repeat F-box1/GIGANTEA and CRY2/CIB1.

Light-inducible systems allow spatiotemporal control of a variety of biological activities. Here, we report newly optimized optogenetic tools to induce transcription with light in mammalian cells, using the Arabidopsis photoreceptor Flavin Kelch-repeat F-box 1 (FKF1) and its binding partner GIGANTEA (GI) as well as CRY2/CIB1. By combining the mutagenesis of FKF1 with the optimization of a split FKF1/GI dimerized Gal4-VP16 transcriptional system, we identified constructs enabling significantly improved light-triggered transcriptional induction. In addition, we have improved the CRY2/CIB1-based light-inducible transcription with split construct optimization. The improvements regarding the FKF1/GI- and CRY2/CIB1-based systems will be widely applicable for the light-dependent control of transcription in mammalian cells.

Dual optical recordings for action potentials and calcium handling in induced pluripotent stem cell models of cardiac arrhythmias using genetically encoded fluorescent indicators.

Reprogramming of human somatic cells to pluripotency has been used to investigate disease mechanisms and to identify potential therapeutics. However, the methods used for reprogramming, in vitro differentiation, and phenotyping are still complicated, expensive, and time-consuming. To address the limitations, we first optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. This method allowed us to generate multiple lines of integration-free and feeder-free induced pluripotent stem cells (iPSCs) from seven patients with cardiac diseases and three controls. Second, we differentiated human iPSCs derived from patients with Timothy syndrome into cardiomyocytes using a monolayer differentiation method. We found that Timothy syndrome cardiomyocytes showed slower, irregular contractions and abnormal calcium handling compared with the controls. The results are consistent with previous reports using a retroviral method for reprogramming and an embryoid body-based method for cardiac differentiation. Third, we developed an efficient approach for recording the action potentials and calcium transients simultaneously in control and patient cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R-GECO1. The dual optical recordings enabled us to observe prolonged action potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We confirmed that roscovitine rescued the phenotypes in Timothy syndrome cardiomyocytes and that these findings were consistent with previous studies using conventional electrophysiological recordings and calcium imaging with dyes. The approaches using our optimized methods and dual optical recordings will improve iPSC applicability for disease modeling to investigate mechanisms underlying cardiac arrhythmias and to test potential therapeutics.