Lysosomal associated membrane protein 2 (LAMP2) is physiologically implicated in autophagy. A genetic LAMP2 defect causes Danon disease, which consists of two major phenotypes of myopathy and cardiomyopathy. In addition, arteriopathy may manifest on rare occasions but the pathological basis remains unknown. We encountered two Danon families that developed small-vessel vasculopathy in the coronary or cerebral arteries. To investigate the underlying mechanisms, we characterized the biological features of LAMP-2–deficient mice and cultured cells. LAMP-2–deficient mice at 9–24 months of age showed medial thickening with luminal stenosis due to proliferation of vascular smooth muscle cells (VSMC) in muscular arteries. Ultrastructural analysis of VSMC revealed various autophagic vacuoles scattered throughout the cytoplasm, suggesting impaired autophagy of long-lived metabolites and degraded organelles (i.e., mitochondria). The VSMC in Lamp2 null mice expressed more vimentin but less α-smooth muscle actin (α-SMA), indicating a switch from contractile to synthetic phenotype. Silencing of LAMP2 in cultured human brain VSMC showed the same phenotypic transition with mitochondrial fragmentation, enhanced mitochondrial respiration, and overproduction of reactive oxygen species (ROS). These findings indicate that LAMP-2 deficiency leads to arterial medial hypertrophy with the phenotypic conversion of VSMC, resulting from age-dependent accumulation of cellular waste generated by aberrant autophagy.

Objective SSc is a connective tissue disease with multisystem disorder induced by the inflammation and fibrosis following T and B cell abnormalities. Follicular helper CD4+ T (TFH) cells play a crucial role in the formation of germinal centres and specialize in interacting to aid B cell differentiation. We aimed to investigate TFH cells and their subsets to evaluate their involvement with B cell alteration in SSc. Method Circulating TFH cells (cTFH), B cells and their subsets were assessed by flow cytometry. The concentration of serum cytokines was measured by cytokine array assay. Immunohistochemistry and IF were performed to evaluate the migration of TFH cells in SSc skin lesions. Results The proportion of cTFH cells did not differ from controls, but their subsets were imbalanced in SSc patients. The frequency of TFH 1 was increased and correlated with ACA titre, serum IgM or CRP levels of patients, and cytokine concentrations of IL-21 and IL-6 that induce B cell differentiation in SSc. cTFH cells from SSc showed activated phenotype with expressing higher cytokine levels compared with controls. The frequency of TFH 17 was also increased, but was not correlated with a high level of Th17 cytokines in patients’ sera. Furthermore, infiltration of TFH cells was found in skin lesion of SSc patients. Conclusion We here describe an imbalance of cTFH toward TFH 1 that may induce B cell alteration through IL-21 and IL-6 pathways and promote inflammation, contributing to the pathogenesis of SSc disease.

Background Cardiac amyloidosis, a progressive cardiac disease, results from the accumulation of undegraded proteinaceous substrates in the extracellular matrix of the heart. It may present as acute coronary syndrome (ACS); therefore, a clear distinction remains challenging in clinical practice. We describe a case of cardiac amyloidosis mimicking ACS. Case summary A 72-year-old man experienced chest discomfort for 2 days. He gradually developed dyspnoea during the preceding month. Electrocardiogram (ECG) showed sinus rhythm with right bundle branch block and low voltage. Echocardiography revealed concentric left ventricular thickening, biatrial dilation, and preserved ejection fraction with predominantly left ventricular basal hypokinesis. Serial testing of the cardiac biomarkers showed persistently increased high-sensitive cardiac troponin T levels and normal serum creatine kinase myocardial band levels. He was diagnosed with ACS with haemodynamic stability. However, coronary angiography demonstrated non-obstructive coronary arteries. Furthermore, significant macroglossia and periorbital purpura were noticed. Laboratory investigations revealed elevated serum immunoglobulin free light chain (FLC) kappa and lambda levels with an increased FLC ratio. Histological analysis of the biopsied abdominal skin confirmed amyloidosis. Discussion Cardiac amyloidosis often presents as restrictive cardiomyopathy. The usual symptoms include dyspnoea and peripheral oedema. Chest pain may manifest rarely, leading to misdiagnosis as coronary artery disease. Some findings suggestive of cardiac amyloidosis include clinical signs such as amyloid deposits, dyspnoea, low ECG voltage, and basal-predominant hypokinesis with relative apical sparing in echocardiography. Serum FLC test and abdominal skin biopsy can confirm the diagnosis of amyloidosis when a myocardial biopsy is not feasible.

The purpose of this study is to present a comprehensive review of the use of structural equation modeling (SEM) in augmented reality (AR) studies in the context of the COVID-19 pandemic. IEEE Xplore Scopus, Wiley Online Library, Emerald Insight, and ScienceDirect are the main five data sources for data collection from Jan 2020 to May 2021. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach was used to conduct the analysis. At the final stage, 53 relevant publications were included for analysis. Variables such as the number of participants in the study, original or derived hypothesized model, latent variables, direct/indirect contact with users, country, limitation/suggestion, and keywords were extracted. The results showed that a variety of external factors were used to construct the SEM models rather than using the parsimonious ones. The reports showed a fair balance between the direct and indirect methods to contact participants. Despite the COVID-19 pandemic, few publications addressed the issue of data collection and evaluation methods, whereas video demonstrations of the augmented reality (AR) apps were utilized. The current work influences new AR researchers who are searching for a theory-based research model in their studies.