Middle East Respiratory Syndrome Coronavirus: What Does a Radiologist Need to Know?

OBJECTIVE: The overarching goal of this article is to provide radiologists with the most up-to-date information regarding the underlying epidemiology, pathophysiology, clinical features, and imaging findings related to Middle East respiratory syndrome coronavirus (MERS-CoV), a potentially deadly new infection. CONCLUSION: An increased awareness of MERS-CoV and an understanding of the radiologic features of MERS-CoV can improve the early assessment and monitoring of this new infection. Radiologists can provide information based on chest radiographic and CT scores that can be helpful for patient management and predicting prognosis.

Faulty initiation of proteoglycan synthesis causes cardiac and joint defects.

Proteoglycans are a major component of extracellular matrix and contribute to normal embryonic and postnatal development by ensuring tissue stability and signaling functions. We studied five patients with recessive joint dislocations and congenital heart defects, including bicuspid aortic valve (BAV) and aortic root dilatation. We identified linkage to chromosome 11 and detected a mutation (c.830G>A, p.Arg277Gln) in B3GAT3, the gene coding for glucuronosyltransferase-I (GlcAT-I). The enzyme catalyzes an initial step in the synthesis of glycosaminoglycan side chains of proteoglycans. Patients' cells as well as recombinant mutant protein showed reduced glucuronyltransferase activity. Patient fibroblasts demonstrated decreased levels of dermatan sulfate, chondroitin sulfate, and heparan sulfate proteoglycans, indicating that the defect in linker synthesis affected all three lines of O-glycanated proteoglycans. Further studies demonstrated that GlcAT-I resides in the cis and cis-medial Golgi apparatus and is expressed in the affected tissues, i.e., heart, aorta, and bone. The study shows that reduced GlcAT-I activity impairs skeletal as well as heart development and results in variable combinations of heart malformations, including mitral valve prolapse, ventricular septal defect, and bicuspid aortic valve. The described family constitutes a syndrome characterized by heart defects and joint dislocations resulting from altered initiation of proteoglycan synthesis (Larsen-like syndrome, B3GAT3 type).

Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients.

Spondylo-meta-epiphyseal dysplasia (SMED) with short limbs and abnormal calcifications (SMED-SL) is a rare, autosomal recessive human growth disorder, characterized by disproportionate short stature, short limbs, short broad fingers, abnormal metaphyses and epiphyses, platyspondyly and premature calcifications. Recently, three missense mutations and one splice-site mutation in the DDR2 gene were identified as causative genetic defects for SMED-SL, but the underlying cellular and biochemical mechanisms were not explored. Here we report a novel DDR2 missense mutation, c.337G>A (p.E113K), that causes SMED-SL in two siblings in the United Arab Emirates. Another DDR2 missense mutation, c.2254C>T (p.R752C), matching one of the previously reported SMED-SL mutations, was found in a second affected family. DDR2 is a plasma membrane receptor tyrosine kinase that functions as a collagen receptor. We expressed DDR2 constructs with the identified point mutations in human cell lines and evaluated their localization and functional properties. We found that all SMED-SL missense mutants were defective in collagen-induced receptor activation and that the three previously reported mutants (p.T713I, p.I726R and p.R752C) were retained in the endoplasmic reticulum. The novel mutant (p.E113K), in contrast, trafficked normally, like wild-type DDR2, but failed to bind collagen. This finding is in agreement with our recent structural data identifying Glu113 as an important amino acid in the DDR2 ligand-binding site. Our data thus demonstrate that SMED-SL can result from at least two different loss-of-function mechanisms: namely defects in DDR2 targeting to the plasma membrane or the loss of its ligand-binding activity.

Jewish Liturgy During the Early Stages of the COVID-19 Pandemic: Vignettes from Boston Suburbs.

In March 2020, because of the COVID-19 pandemic, American synagogues locked their doors. This required emergency planning for Passover observances, and then gradually less panicked planning for subsequent liturgies. Based primarily on the experiences of three Boston-area synagogues, Reform, Conservative, and Orthodox, and interviews with their rabbis, this article compares the liturgical responses of Jews in these three movements, offering explanations for their different approaches. It also briefly traces, where appropriate, their resumption of services over the summer and their plans for the fall holy days.

Follow-up chest radiographic findings in patients with MERS-CoV after recovery.

PURPOSE: To evaluate the follow-up chest radiographic findings in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) who were discharged from the hospital following improved clinical symptoms. MATERIALS AND METHODS: Thirty-six consecutive patients (9 men, 27 women; age range 21-73 years, mean ± SD 42.5 ± 14.5 years) with confirmed MERS-CoV underwent follow-up chest radiographs after recovery from MERS-CoV. The 36 chest radiographs were obtained at 32 to 230 days with a median follow-up of 43 days. The reviewers systemically evaluated the follow-up chest radiographs from 36 patients for lung parenchymal, airway, pleural, hilar and mediastinal abnormalities. Lung parenchyma and airways were assessed for consolidation, ground-glass opacity (GGO), nodular opacity and reticular opacity (i.e., fibrosis). Follow-up chest radiographs were also evaluated for pleural thickening, pleural effusion, pneumothorax and lymphadenopathy. Patients were categorized into two groups: group 1 (no evidence of lung fibrosis) and group 2 (chest radiographic evidence of lung fibrosis) for comparative analysis. Patient demographics, length of ventilations days, number of intensive care unit (ICU) admission days, chest radiographic score, chest radiographic deterioration pattern (Types 1-4) and peak lactate dehydrogenase level were compared between the two groups using the student t-test, Mann-Whitney U test and Fisher's exact test. RESULTS: Follow-up chest radiographs were normal in 23 out of 36 (64%) patients. Among the patients with abnormal chest radiographs (13/36, 36%), the following were found: lung fibrosis in 12 (33%) patients GGO in 2 (5.5%) patients, and pleural thickening in 2 (5.5%) patients. Patients with lung fibrosis had significantly greater number of ICU admission days (19 ± 8.7 days; P value = 0.001), older age (50.6 ± 12.6 years; P value = 0.02), higher chest radiographic scores [10 (0-15.3); P value = 0.04] and higher peak lactate dehydrogenase levels (315-370 U/L; P value = 0.001) when compared to patients without lung fibrosis. CONCLUSION: Lung fibrosis may develop in a substantial number of patients who have recovered from Middle East respiratory syndrome coronavirus (MERS-CoV). Significantly greater number of ICU admission days, older age, higher chest radiographic scores, chest radiographic deterioration patterns and peak lactate dehydrogenase levels were noted in the patients with lung fibrosis on follow-up chest radiographs after recovery from MERS-CoV.