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BACKGROUND In humans, wood dust is a carcinogen. Indeed, a strong association between wood dust and lung cancer risk has been reported in woodworkers, as well as in the general population. CASE REPORT The patient was a 58-year-old man with follicular B-cell lymphoma. In the 10 years preceding the cancer diagnosis, he lived within 1/4 mile of a paper mill, where wood was processed. Computed tomography of the chest, abdomen, and pelvis revealed right hilar, mediastinal, abdominal, and retroperitoneal lymphadenopathy, bilateral pleural effusions, and a large soft-tissue mass infiltrating the small bowel mesentery. Analysis of the pleural fluid revealed the presence of a web of thin filopodia-like filaments, which trapped clusters of mesothelial cells and atypical lymphocytes. Single tubular filaments, morphologically similar to tunneling nanotubes, were seen originating from atypical lymphocytes and reaching neighboring cells. Furthermore, long, thick, cylindrical fibers of unknown nature, probably from the external environment, were also observed. CONCLUSIONS Because the patient lived in an unhealthy environment for many years, the possibility that his clinical condition was related to exposure to toxic emissions should be entertained. Considered in this context, the foreign fibers in his pleural fluid could be a direct consequence of inhalation of contaminants in the polluted air.

In this systematic review article, we aim to summarize the most up-to-date evidence regarding elevations of cardiac troponin, especially in clinical scenarios other than obstructive coronary artery disease. The accurate interpretation of raised cardiac troponin is challenging because it relies on unconfirmed postulations and dogmatic knowledge (e.g., the exclusive provenience of cardiac troponin from cardiac myocytes), based on which every troponin elevation is assumed to definitely indicate myocardial damage. Indeed, the investigation of the pathophysiologic mechanism leading to the release in the bloodstream of cardiac biomarkers should be the first step of the diagnostic process to fully understand the clinical significance of the elevated serum levels and identify the best management. A prominent effort should be put in place to identify the contribution of potential confounding factors, both cardiac and non-cardiac in etiology, with the ability to affect synthesis and clearance of cardiac biomarkers. Regardless of the underlying cause, it is well established that cardiovascular biomarkers are increasingly useful to further risk stratification and prognosticate patients. Accordingly, we sought to clarify the meaning and impact of elevated cardiac troponin in those frequently encountered real-world scenarios presenting clinicians with a diagnostic dilemma, with the final goal of facilitating the diagnosis and help optimize individually tailored treatment strategies.

BACKGROUND Urocortin (Ucn) is a member of the hypothalamic corticotrophin-releasing factor family and has been shown to reduce cell death in the heart caused by ischemia/reperfusion (I/R) injury. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor known to function as a pro-survival and anti-apoptotic factor, whose activation depends on a variety of cytokines, including IL-6. A recent study demonstrated that urocortin induced IL-6 release from cardiomyocytes in a CRF-R2-dependent manner, suggesting a possible link between CRF-R2 stimulation and STAT3 activation. MATERIAL AND METHODS Experimental work was carried out in HL-1 cardiac myocytes exposed to serum starvation for 16-24 h. RESULTS Ucn stimulation led to IL-6 expression and release from mouse atrial HL-1 cardiomyocytes. Ucn treatment led to rapid phosphorylation of JAK2, which was blocked by the protein synthesis inhibitor cycloheximide or the JAK inhibitor AG490. Urocortin treatment induced STAT3 phosphorylation at Y705 and S727 through transactivation of JAK2 in an IL-6-dependent manner, but had no effect on STAT1 activity. Kinase inhibition experiments revealed that urocortin induces STAT3 S727 phosphorylation through ERK1/2 and Y705 phosphorylation through Src tyrosine kinase. In line with this finding, urocortin failed to induce phosphorylation of Y705 residue in SYF cells bearing null mutation of Src, while phosphorylation of S727 residue was unchanged. CONCLUSIONS Here, we have shown that Ucn induces activation of STAT3 through diverging signaling pathways. Full understanding of these signaling pathways will help fully exploit the cardioprotective properties of endogenous and exogenous Ucn.

BACKGROUND Although originally described as a survival mechanism, it is unknown whether and to what extent autophagy is implicated in the terminal stages of heart failure. Here, we studied magnitude and evolution of autophagy in patients with intractable heart failure. MATERIAL AND METHODS Myocardial samples were obtained from 22 patients with ischemic cardiomyopathy and idiopathic dilated cardiomyopathy who were undergoing cardiac transplantation. Hearts from 11 patients who died from non-cardiac causes were used as control samples. Autophagy was evaluated by immunostaining with a monoclonal microtubule associated protein light chain 3 (LC3)-II antibody, while the relationship of autophagy with apoptosis and oncosis was assessed by double staining with TUNEL (terminal deoxynucleotidyl transferase - mediated deoxyuridine triphosphate nick end labeling) assay and complement 9 (C9) immunological staining, respectively. In addition, several necroptotic markers, including RIP1 and RIP3 (receptor interacting protein kinase 1 and 3), anti-C3 (cleaved-caspase-3), and anti-NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) were assessed by immunohistochemistry. RESULTS Anti-LC3-II staining was detected in 8.7±1.6% of the heart failure patient heart samples and in 1.2±0.3% of control patient heart samples. Vacuole formation started at one nuclear pole, before becoming bipolar and involving the cytosol. Subsequently, the autophagic process extended also to the nuclei, which underwent a progressive vacuolization and disintegration, assuming a peculiar "strawberry like appearance". Myocytes with extensive vacuole formation exhibited nuclear degeneration, which was associated with TUNEL, C3, C9, RIP1, and RIP3 positive staining. Conversely, myocytes with less extensive vacuole formation showed RIP1 and NF-κB positive staining, though not positivity for other cell death markers. CONCLUSIONS Autophagy was extensively detected in end-stage heart failure and its progression, resulted in secondary cell death, with occurrence of oncosis and necroptosis exceeding that of apoptosis. Conversely, activation of the RIP1/NF-κB pathway was associated with cell survival.