Right heart thrombus in transit and peripherally inserted central catheters.

Right heart thrombus in transit or "free-floating right heart thrombus" is defined as thrombus(i) arising from the deep veins that embolises to the right atrium or right ventricle before reaching the pulmonary vasculature. It is almost always associated with pulmonary thromboembolism and is a medical emergency with reported mortality rates of over 40%. We present two cases of right heart thrombus in transit with pulmonary thromboembolism resulting from venous thrombosis associated with peripherally inserted central catheters that were managed with different approaches. The cases highlight that clinicians should have a low threshold to utilise imaging modalities such as computerised tomography and transthoracic echocardiography when there is an untoward change in physiological parameters among patients with peripherally inserted central catheters, particularly those with risk factors for peripherally inserted central catheter associated venous thrombosis. Furthermore, procedural optimisation surrounding peripherally inserted central catheters, such as insertion technique and choice of lumen size, is underscored.

Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID-19 patients.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID-19 may impact the development of the MDR. METHODS: Blood and skin samples from COVID-19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID-MDR), healthy controls, non-COVID-19-related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high-throughput multiplexed proteomic profiling of serum were performed. RESULTS: IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8+ T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID-MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID-MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed upregulation of various inflammatory mediators (IL-4, IL-5, IL-6, TNF, and IFN-γ), eosinophil and Mo/Mac -attracting chemokines (MCP-2, MCP-3, MCP-4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID-MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features. CONCLUSION: A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8+ T cells in severe COVID-19 patients, which in turn may impact the development of MDR.

Exploring Teacher Job Satisfaction in Rural China: Prevalence and Correlates.

Extant research continues to establish the importance of teacher job satisfaction to student performance, yet teacher job satisfaction remains under-investigated in rural China. In this paper, we examine the prevalence and correlates of teacher job satisfaction. Using data from 634 teachers across 120 schools in rural China, we find an alarmingly high prevalence of teacher job dissatisfaction: roughly 21% of rural teachers were less than satisfied with their jobs. In addition, we find that several individual- and school-level characteristics, including being a male teacher, being a homeroom teacher, not having a management role in school, being a middle-aged teacher, and a school's boarding status, are correlated with teacher job dissatisfaction. In sum, the results demonstrate a need for further research and policy interventions to improve teacher job satisfaction in rural schools.

Antagonism of interferon signaling by fibroblast growth factors promotes viral replication.

Fibroblast growth factors (FGFs) play key roles in the pathogenesis of different human diseases, but the cross-talk between FGFs and other cytokines remains largely unexplored. We identified an unexpected antagonistic effect of FGFs on the interferon (IFN) signaling pathway. Genetic or pharmacological inhibition of FGF receptor signaling in keratinocytes promoted the expression of interferon-stimulated genes (ISG) and proteins in vitro and in vivo. Conversely, FGF7 or FGF10 treatment of keratinocytes suppressed ISG expression under homeostatic conditions and in response to IFN or poly(I:C) treatment. FGF-mediated ISG suppression was independent of IFN receptors, occurred at the transcriptional level, and required FGF receptor kinase and proteasomal activity. It is not restricted to keratinocytes and functionally relevant, since FGFs promoted the replication of herpes simplex virus I (HSV-1), lymphocytic choriomeningitis virus, and Zika virus. Most importantly, inhibition of FGFR signaling blocked HSV-1 replication in cultured human keratinocytes and in mice. These results suggest the use of FGFR kinase inhibitors for the treatment of viral infections.

The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity.

To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that Cerox1, an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p. Increased abundance of Cerox1 cooperatively elevates complex I subunit protein abundance and enzymatic activity, decreases reactive oxygen species production, and protects against the complex I inhibitor rotenone. Cerox1 function is conserved across placental mammals: human and mouse orthologues effectively modulate complex I enzymatic activity in mouse and human cells, respectively. Cerox1 is the first lncRNA demonstrated, to our knowledge, to regulate mitochondrial oxidative phosphorylation and, with miR-488-3p, represent novel targets for the modulation of complex I activity.