MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress

MZB1 (pERp1) is a B-cell-specific and endoplasmic reticulum (ER)-localized protein implicated in antibody secretion and integrin-mediated cell adhesion. Here, we examine the role of MZB1 in vivo by conditional gene inactivation in the mouse germline and at different stages of B lymphopoiesis. Deletion of MZB1 impairs humoral immune responses and antibody secretion in plasma cells that naturally undergo ER stress. In addition, we found that experimental induction of ER stress by tunicamycin injections in mice results in a block of pro-B-cell to pre-B-cell differentiation specifically in Mzb1^−/− mice. A similar developmental block was observed in Mzb1^fl/flmb1^Cre mice, whereby a Cre recombinase-induced genotoxic stress unmasks a role for MZB1 in the surface expression of immunoglobulin µ heavy chains (µHCs). MZB1 associates directly with the substrate-specific chaperone GRP94 (also called HSP90B1 or gp96) in an ATP-sensitive manner and is required for the interaction of GRP94 with µHCs upon ER stress. Thus, MZB1 seems to act as a substrate-specific cochaperone of GRP94 that enables proper biosynthesis of µHCs under conditions of ER stress.     

Prosthetic mitral valve thrombosis,malfunction, and paroxysmal mitral regurgitation

Intermittent dysfunction of mechanical mitral valve prosthesis is an uncommon condition. It carries serious clinical implications if unrecognized. Here, we present a case of a 28‐year‐old female with a history of rheumatic multivalvular disease, for which she had undergone double valve replacement and tricuspid annuloplasty. Six months later, she presented with heart failure. Clinical examination revealed intermittent loss of closing clicks followed by a pansystolic murmur at the apex, suggestive of mitral prosthetic valve dysfunction. We highlight the echocardiographic findings of paroxysmal mitral valvular regurgitation secondary to prosthetic valve malfunction secondary to prosthetic valve thrombosis.     

Audio recordings of mindfulness-based stress reduction training to improve cancer patients’ mood and quality of life—a pilot feasibility study

Purpose  

Mindfulness-based stress reduction (MBSR), typically taught in eight weekly classes, helps patients cope with illness, including cancer. Current research is almost exclusively based on post-treatment class attendance. Research suggests that short courses and alternative delivery techniques may also be beneficial. This pilot study assessed whether it would be feasible for cancer patients receiving chemotherapy to listen to MBSR audio recordings individually during treatment and at home and evaluate whether the intervention shows preliminary evidence of efficacy to improve patients’ mood and quality of life (QoL).     

False positive retroaortic left circumflex coronary artery in a patient with atrial septal defect

Retroaortic course of coronary artery is a relative contraindication for device closure of an atrial septal defect. In this brief report, we demonstrate, for the first time, inferior aortic recess mimicking retroaortic left circumflex coronary artery in a patient with atrial septal defect. This distinction is important to avoid spurious diagnosis of anomalous coronary artery denying patient a chance of nonsurgical closure of atrial septal defect.     

Unruptured sinus of Valsalva aneurysm mimicking as right atrial tumor

Sinus of Valsalva aneurysm is a rare congenital cardiac abnormality and is usually diagnosed when it ruptures. An asymptomatic 55‐year‐old male of unruptured sinus of Valsalva aneurysm of noncoronary cusp was on medical follow‐up. At 2‐year follow‐up, there was thrombus formation in the aneurysm, mimicking right atrium tumor on 2D transthoracic echocardiography. Cardiac computed tomography showed filling defect in the aneurysm suggestive of thrombus. Considering the high risk of systemic emboli surgery was performed, and aneurysm was repaired with Dacron patch.