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Mitochondria are cytoplasmic organelles having a fundamental role in the regulation of neural stem cell (NSC) fate during neural development and maintenance. During embryonic and adult neurogenesis, NSCs undergo a metabolic switch from glycolytic to oxidative phosphorylation with a rise in mitochondrial DNA (mtDNA) content, changes in mitochondria shape and size, and a physiological augmentation of mitochondrial reactive oxygen species which together drive NSCs to proliferate and differentiate. Genetic and epigenetic modifications of proteins involved in cellular differentiation (Mechanistic Target of Rapamycin), proliferation (Wingless-type), and hypoxia (Mitogen-activated protein kinase)–and all connected by the common key regulatory factor Hypoxia Inducible Factor-1A–are deemed to be responsible for the metabolic shift and, consequently, NSC fate in physiological and pathological conditions. Both primary mitochondrial dysfunction due to mutations in nuclear DNA or mtDNA or secondary mitochondrial dysfunction in oxidative phosphorylation (OXPHOS) metabolism, mitochondrial dynamics, and organelle interplay pathways can contribute to the development of neurodevelopmental or progressive neurodegenerative disorders. This review analyses the physiology and pathology of neural development starting from the available in vitro and in vivo models and highlights the current knowledge concerning key mitochondrial pathways involved in this process. [ABSTRACT FROM AUTHOR]

The Feline Leukemia Virus Subgroup C Receptor 1a (FLVCR1a) is a transmembrane heme exporter essential for embryonic vascular development. However, the exact role of FLVCR1a during blood vessel development remains largely undefined. Here, we show that FLVCR1a is highly expressed in angiogenic endothelial cells (ECs) compared to quiescent ECs. Consistently, ECs lacking FLVCR1a give rise to structurally and functionally abnormal vascular networks in multiple models of developmental and pathologic angiogenesis. Firstly, zebrafish embryos without FLVCR1a displayed defective intersegmental vessels formation. Furthermore, endothelial-specific Flvcr1a targeting in mice led to a reduced radial expansion of the retinal vasculature associated to decreased EC proliferation. Moreover, Flvcr1a null retinas showed defective vascular organization and loose attachment of pericytes. Finally, adult neo-angiogenesis is severely affected in murine models of tumor angiogenesis. Tumor blood vessels lacking Flvcr1a were disorganized and dysfunctional. Collectively, our results demonstrate the critical role of FLVCR1a as a regulator of developmental and pathological angiogenesis identifying FLVCR1a as a potential therapeutic target in human diseases characterized by aberrant neovascularization. [ABSTRACT FROM AUTHOR]

COVID-19 has dramatically affected working forces. We aim to report our occupational medicine service's experience in managing suspected COVID-19 cases during the pandemic through a retrospective observational study. We compared the number of days employees were absent from work due to flu-like symptoms from March 2020 to February 2021 to the same period the previous year (2019-2020). Two hundred thirty-four patients (+47.2% compared to the previous year) who tested negative for SARS-CoV-2 reported flu-like symptoms; the number of days of absence from work was 2812 (+190.2% compared to the previous year). On average, employees with flu-like symptoms lost 12.07 working days compared to 6.12 in the previous year (p<0.0001). In conclusion, in our sample COVID-19 has increased the number of working day loss. However, our approach proved to be important, especially during the first months of the pandemic, to limit SARS-CoV-2 spread in workplaces. [ABSTRACT FROM AUTHOR]

Background: T-lymphocyte activation within atherosclerotic plaque, and widespread to the myocardium, has been shown in patients with acute coronary syndromes. Objective: To investigate the presence of T-lymphocyte infiltrate at different stages of acute coronary syndromes by studying patients with sudden coronary death, acute myocardial infarction IAMI) and healed infarction, in comparison with patients with myocarditis and patients with non-ischaemic heart failure. Methods: 72 cases were studied at autopsy: 12 dying of sudden coronary death (group 1), 12 dying <4 weeks (group 2) and 12 dying >4 months after AMI (group 3), 12 with active lymphocytic myocarditis (group 4), 12 with hypertensive heart disease (group 51, and 12 control subjects (group 6). Light microscopy was performed to measure the number of activated T-lymphocytes ICD3+/ DR+l in the myocardium and coronary artery wall, and intercellular adhesion molecule-i (ICAM-1) expression in the myocardium. Results: Activated T-lymphocyte infiltrates and CAM-i myocardial expression in both remote and pen-infarction regions and activated T-lymphocytes within the epicardial coronary artery wall of both the infarct- and non-infarct- related arteries were found in groups 1, 2 and 3, whereas myocardial, but not coronary, infiltrates were found in groups 4 (p'

Objective: To test the hypothesis that impaired coronary and myocardial blood flow are linked with increased myocyte apoptosis, thus establishing a link between pressure overload and left ventricular (LV) remodelling. Methods and results: Peak diastolic coronary blood flow velocity (CBFV) was evaluated at transthoracic Doppler echocardiography, and signal intensity (SI) and the rate of SI rise (β) were measured at myocardial contrast echocardiography in 11 patients with severe aortic stenosis and LV hypertrophy. In the same patients, biopsies were obtained from the anterolateral LV free wall during surgery and analysed for cardiomyocyte apoptosis. LV mass corrected CBFV (CBFVI) was significantly lower in patients than in controls (median 0.100 cm g/s (interquartile range 0.07–0.115) v 0.130 cm g/s (0.130–0.160), p = 0.002). Similarly, SI*β was significantly lower in patients than in controls (11 1/s (8–66) v 83 1/s (73–95), p = 0.001). Apoptotic rate was increased in aortic stenosis more than 100-fold versus controls (1.2% (0.8–1.4) v 0.01% (0.01–0.01), p < 0.001) and inversely correlated with lower CBFVI and SI*β (r = -0.77, p = 0.001 for both). Conclusions: Patients with severe aortic stenosis and LV hypertrophy have impaired myocardial perfusion, which is associated with enhanced cardiomyocyte apoptosis. Impaired myocardial perfusion and the ensuing oxygen demand-supply imbalance may, at least partially, be responsible for increased apoptosis and possible transition to heart failure, thus establishing a link between pressure overload, LV remodelling, and heart failure. [ABSTRACT FROM AUTHOR]

Background: Apoptosis is a key feature in postinfarction remodelling leading to progressive myocyte loss. Both proapoptotic and antiapoptotic factors contribute to the delicate balance between death and survival. The survivin pathway has emerged as essential in the control of apoptosis, although its role in heart disease is unknown. Am: To evaluate survivin expression after acute myocardial infarction (AMI). Methods: Survivin expression was assessed immunohistochemically in the peri-infarct and remote viable myocardium in 17 consecutive patients who died 1-30 weeks after AMI and in Four control hearts. Results: Survivin was expressed by myocytes in the peri-infarct area in eight patients and in the remote region in 13 patients. The rate of survivin expression after AMI was significantly higher in the remote versus peri-infard regions and compared with control hearts. Its expression was inversely associated with the presence of dilated cardiopathy and of apoptosis, independently from the gross pathology infarct size. Conclusions: Survivin myocardial expression after AM! may be associated with the survival of at risk myocardium and may be indicative of more favourable remodelling after AMI. These findings identify a potential new target for the treatment of postinfarction remodelling. [ABSTRACT FROM AUTHOR]

Objective: In our previous work, patients affected by SSc were treated with intravenous urokinase and showed clinical improvement. In this study we used microscopy to document ultrastructural alterations occurring in sclerodermic skin from SSc patients treated with urokinase.Methods: Ten patients with SSc were selected for this study. Skin biopsies were taken from the medial side of the right forearm on the third proximal on the volar surface. The patients were then treated with urokinase for 7 consecutive days. At the end of the treatment, the patients were examined and a new skin biopsy was taken close to the above-mentioned zone of the forearm for optic and electron microscopy examination.Results: The patients showed a gradual improvement of the skin after urokinase treatment. Raynaud's appeared to be less intense, and they had an increased articular range, with the restoration of movements that had previously been limited. Histological findings showed that, after treatment, skin alterations appeared attenuated, in particular the connective tissue showed a decreased density and inflammatory infiltrate was slight. Electron microscopy findings showed that collagen fibres appeared to have a more regular diameter, and the capillary vessels' lining was thicker, with fewer pinocytotic vesicles.Conclusion: These observations show that urokinase treatment seems to be an interesting therapeutic strategy to consider for the treatment of SSc. [ABSTRACT FROM AUTHOR]