91 research outputs found
Quali effetti hanno avuto le misure di contenimento del COVID-19 sul benessere occupazionale? Uno studio sui lavoratori delle piccole e medie imprese italiane.
No full textIntroduzione. Le piccole e medie imprese italiane (PMI) sono state duramente colpite dalle misure di
contenimento dell’emergenza sanitaria da COVID-19. Ad oggi, non è ancora chiaro quale impatto queste
misure possano aver avuto sul benessere occupazionale dei lavoratori impiegati nelle PMI.
Obiettivi. Il presente studio si propone di esplorare se e come la chiusura durante il lockdown di alcune PMI,
possa aver avuto un impatto sulla percezione della crisi economica e sulla salute psico-fisica dei lavoratori in
esse impiegati.
Metodo. 101 lavoratori impiegati in PMI localizzate in una provincia del Sud Italia hanno compilato un
questionario self-report che includeva: apertura durante il lockdown (1 item), paura della crisi economica (Fear
of the Economic Crisis Scale), auto-efficacia percepita nel fronteggiare il COVID-19 (COVID-19-related
coping self-efficacy) e salute psico-fisica (General Health Questionnaire). Le analisi dei dati hanno previsto
modelli di mediazione e mediazione moderata.
Risultati. La chiusura durante il lockdown si associa positivamente con la paura della crisi economica (β=.72,
p<.01) che, a sua volta, porta i lavoratori delle PMI a sperimentare sintomi di malessere psico-somatico (β=.20,
p<.001). Tuttavia, l’impatto negativo della paura della crisi economica sul loro stato di salute è confermato
soltanto per coloro che possiedono bassi (β=.31, p<.001) o moderati (β=.21, p<.001) livelli di auto-efficacia
percepita nel fronteggiare il COVID-19, ma non per coloro con elevati livelli di auto-efficacia (β=.08, p=.20).
Limiti. Questo studio trasversale si basa esclusivamente su misure self-report e su un campione esiguo di
lavoratori provenienti da un’unica provincia italiana.
Aspetti innovativi. Analizzando gli effetti di una specifica misura di lockdown sul benessere occupazionale dei
lavoratori impiegati nelle PMI, questa ricerca arricchisce la letteratura sugli effetti dell’emergenza sanitaria.
Inoltre, individuando nell’auto-efficacia percepita un’importante fattore di protezione, questo studio fornisce
supporto circa l’importanza di fornire a tali lavoratori coping effectiveness training
Prolonged darkness reduces liver fibrosis in a mouse model of primary sclerosing cholangitis by miR-200b down-regulation
No full textMelatonin therapy or prolonged exposure to complete darkness reduces biliary hyperplasia and liver fibrosis in bile-duct-ligated (BDL) rats; however, no information exists in primary sclerosing cholangitis (PSC). Thus, we aimed to determine the therapeutic effects of prolonged dark therapy or melatonin administration on hepatic fibrosis in the Mdr2(-/-) mouse model of PSC. Melatonin levels, biliary mass, liver fibrosis, angiogenesis and miR-200b expression were evaluated in wild-type and Mdr2(-/-) mice exposed to darkness or melatonin treatment or in male PSC patient samples and healthy controls. Mdr2(-/-) mice were also treated with miR-200b inhibitor or control before evaluating biliary mass, liver fibrosis, and angiogenesis. After overexpression of arylalkylamine N-acetyltransferase (AANAT; the enzyme regulating melatonin synthesis) or inhibition of miR-200b in cholangiocytes and hepatic stellate cells in vitro, we evaluated angiogenesis and fibrosis gene expression. After exposure to darkness or administration of melatonin, Mdr2(-/-) mice show elevated serum melatonin levels and inhibition of biliary mass, along with reduction of liver fibrosis and angiogenesis. miRNA PCR analysis demonstrated that miR-200b expression increased in Mdr2(-/-) mice and PSC patient samples compared with controls and decreased in Mdr2(-/-) mice subjected to dark exposure or melatonin treatment. Inhibition of miR-200b in Mdr2(-/-) ablates biliary proliferation, liver fibrosis, and angiogenesis. In vitro, overexpression of AANAT or inhibition of miR-200b in cholangiocytes and hepatic stellate cells decreased the expression of miR-200b, angiogenesis, and fibrosis genes. Dark therapy or targeting melatonin/miR-200b axis may be important in the management of biliary damage and liver fibrosis in cholangiopathies including PSC.-Wu, N., Meng, F., Zhou, T., Han, Y., Kennedy, L., Venter, J., Francis, H., DeMorrow, S., Onori, P., Invernizzi, P., Bernuzzi, F., Mancinelli, R., Gaudio, E., Franchitto, A., Glaser, S., Alpini G. Prolonged darkness reduces liver fibrosis in a mouse model of primary sclerosing cholangitis by miR-200b down-regulation
Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis
No full textPrimary biliary cholangitis (PBC) primarily targets cholangiocytes and is characterized by liver fibrosis and biliary proliferation. Activation of the secretin (Sct)/secretin receptor (SR) axis, expressed only by cholangiocytes, increases biliary proliferation, liver fibrosis, and bicarbonate secretion. We evaluated the effectiveness of SR antagonist treatment for early-stage PBC. Male and female dominant-negative TGF-β receptor II (dnTGF-βRII) (model of PBC) and wild-type mice at 12 wk of age were treated with saline or the SR antagonist, Sec 5-27, for 1 wk. dnTGF-βRII mice expressed features of early-stage PBC along with enhanced Sct/SR axis activation and Sct secretion. dnTGF-βRII mice had increased biliary proliferation or senescence, inflammation, and liver fibrosis. In dnTGF-βRII mice, there was increased microRNA-125b/TGF-β1/TGF-β receptor 1/VEGF-A signaling. Human early-stage PBC patients had an increase in hepatobiliary Sct and SR expression and serum Sct levels. Increased biliary Sct/SR signaling promotes biliary and hepatic damage during early-stage PBC.-Kennedy, L., Francis, H., Invernizzi, P., Venter, J., Wu, N., Carbone, M., Gershwin, M. E., Bernuzzi, F., Franchitto, A., Alvaro, D., Marzioni, M., Onori, P., Gaudio, E., Sybenga, A., Fabris, L., Meng, F., Glaser, S., Alpini, G. Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis
The secretin/secretin receptor axis modulates liver fibrosis through changes in TGF-β1 biliary secretion
No full textThe secretin/secretin receptor (SR) axis is upregulated by proliferating cholangiocytes during cholestasis. Secretin stimulates biliary proliferation by downregulation of let-7a and subsequent upregulation of the growth-promoting factor NGF. It is not know if the secretin/SR axis plays a role in subepithelial fibrosis observed during cholestasis. Our aim was to determine the role of secretin/SR axis in the activation of biliary fibrosis in animal models and human primary sclerosing cholangitis (PSC). Studies were performed in Wild-type (WT) mice with bile duct ligation (BDL), BDL SR(-/-) mice or Mdr2(-/-) mouse models of cholestatic liver injury. In selected studies, the SR antagonist (Sec 5-27) was used to block the secretin/SR axis. Biliary proliferation and fibrosis were evaluated as well as the secretion of secretin (by cholangiocytes and S cells), the expression of markers of fibrosis, TGF-β1, TGF-β1R, let-7a and downstream expression of NGF. Correlative studies were performed in human control and PSC liver tissue biopsies, serum and bile. SR antagonist reduced biliary proliferation and hepatic fibrosis in BDL WT and Mdr2(-/-) mice. There was decreased expression of let-7a in BDL and Mdr2(-/-) cholangiocytes that was associated with increased NGF expression. Inhibition of let-7a accelerated liver fibrosis due to cholestasis. There was increased expression of TGF-β1, TGF-β1R. Significantly higher expression of secretin, SR and TGF-β1 was observed in PSC patient liver samples compared to healthy controls. In addition, there was higher expression of fibrosis genes and remarkably decreased expression of let-7a and increased expression of NGF compared to the control
Tubular steel structures under static loading-design of rectangular hollow sections (RHS) joints
No full textLAUREA MAGISTRALENegli ultimi decenni, l’uso di profili tubolari nelle costruzioni in acciaio è aumentato grazie ai loro vantaggi rispetto alle sezioni aperte, come il buon comportamento a compressione e torsione. La progettazione dei giunti è parte importante della progettazione delle strutture tubolari. Il presente studio si propone di implementare un metodo rapido per la valutazione della resistenza dei giunti a sezione rettangolare (RHS/SHS) secondo l’Eurocodice 3 e di confrontare le differenze tra la norma corrente e la nuova versione prossima all’entrata in vigore (i.e., EN 1993-1-8:2005 e prEN 1993-1-8:2021, rispettivamente).
Sulla base delle formule contenute nelle due norme, le verifiche di sicurezza dei giunti sono state implementate in un programma Excel/VBA, poi calibrato con esempi disponibili in letteratura. Successivamente, ipotesi geometriche sono state considerate per riscrivere le formule corrispondenti ai modi di rottura condizionanti e i dati riguardanti i giunti verificati sono stati utilizzati per ottenere i rispettivi grafici di progettazione.
È stato poi considerato un caso studio per verificare i vantaggi dell’utilizzo dei suddetti grafici. I risultati hanno mostrato che i valori di resistenza così ottenuti sono marginalmente inferiori a quelli derivati dalle rispettive formule in normativa. È stato inoltre dimostrato che l’utilizzo di profili tubolari in acciai a più alta resistenza, il cui spessore è conseguentemente ridotto, determina una riduzione delle resistenze dei giunti, rendendoli più condizionanti nella progettazione strutturale.
La valutazione comparativa tra le resistenze di progetto dei giunti con le due edizioni dell'Eurocodice 3 ha mostrato una riduzione generalizzata delle resistenze ottenute utilizzando la seconda generazione dell'Eurocodice.Over the past few decades, the use of hollow section profiles in steel construction has increased due to their advantages over open sections, such as good compression and torsional behavior. Joint design is an important part of the of tubular structures design. The aim of the study is to implement a quick procedure to evaluate the ultimate resistance of rectangular hollow section (RHS/SHS) joints according to the Eurocode 3 and compare the differences between the current standard and the soon-to-be-effective updated version (i.e., EN 1993-1-8:2005 and prEN 1993-1-8:2021, respectively).
Based on the formulas in the two norms, joint safety verifications were implemented in an Excel/VBA sheet and calibrated using examples from the literature. Geometry-based hypotheses were used to update the formulas for joints' governing failure modes, and information on the tested joint geometries was used to create the corresponding design charts.
A case study was performed to confirm the benefits of using design charts. The results showed that the resistance values derived from the charts are marginally lower than those derived from the corresponding norm formulas. Additionally, it has been found that the stability of the joints is affected if higher steel grade elements are used.
When comparing the joint design resistances between the two Eurocode versions, the results of the second generation of the Eurocode EN 1993-1-8 have an overall reduction
Melatonin exerts by an autocrine loop antiproliferative effects in cholangiocarcinoma; its synthesis is reduced favoring cholangiocarcinoma growth
No full textHan Y, DeMorrow S, Invernizzi P, Jing Q, Glaser S, Renzi A, Meng F, Venter J, Bernuzzi F, White M, Francis H, Lleo A, Marzioni M, Onori P, Alvaro D, Torzilli G, Gaudio E, Alpini G. Melatonin exerts by an autocrine loop antiproliferative effects in cholangiocarcinoma; its synthesis is reduced favoring cholangiocarcinoma growth. Am J Physiol Gastrointest Liver Physiol 301: G623-G633, 2011. First published July 21, 2011; doi: 10.1152/ajpgi.00118.2011.-Cholangiocarcinoma (CCA) is a devastating biliary cancer. Melatonin is synthesized in the pineal gland and peripheral organs from serotonin by two enzymes, serotonin N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT). Cholangiocytes secrete neuroendocrine factors, including serotonin-regulating CCA growth by autocrine mechanisms. Melatonin exerts its effects by interaction with melatonin receptor type 1A/1B (MT1/MT2) receptors. We propose that 1) in CCA, there is decreased expression of AANAT and ASMT and secretion of melatonin, changes that stimulate CCA growth; and 2) in vitro overexpression of AANAT decreases CCA growth. We evaluated the 1) expression of AANAT, ASMT, melatonin, and MT1/MT2 in human nonmalignant and CCA lines and control and CCA biopsy samples; 2) melatonin levels in nonmalignant and CCA lines, and bile and serum from controls and patients with intrahepatic CCA; 3) effect of melatonin on the growth and expression of AANAT/ASMT and MT1/MT2 in CCA lines implanted into nude mice; and 4) effect of AANAT overexpression on the proliferation, apoptosis, and expression of MT1/MT2 in Mz-ChA-1 cells. The expression of AANAT, ASMT, and melatonin decreased, whereas MT1/MT2 expression increased in CCA lines and biopsy samples. Melatonin secretion decreased in the supernatant of CCA lines and bile of CCA patients. Melatonin decreased xenograft CCA tumor growth in nude mice by increased AANAT/ASMT and melatonin, along with reduced MT1/MT2 expression. Overexpression of AANAT in Mz-ChA-1 cells inhibited proliferation and MT1/MT2 expression and increased apoptosis. There is dysregulation of the AANAT/ASMT/melatonin -> melatonin receptor axis in CCA, which inhibited melatonin secretion and subsequently enhanced CCA growth
Forkhead box A2 regulates biliary heterogeneity and senescence during cholestatic liver injury in mice‡
No full textBiliary-committed progenitor cells (small mouse cholangiocytes; SMCCs) from small bile ducts are more resistant to hepatobiliary injury than large mouse cholangiocytes (LGCCs) from large bile ducts. The definitive endoderm marker, forkhead box A2 (FoxA2), is the key transcriptional factor that regulates cell differentiation and tissue regeneration. Our aim was to characterize the translational role of FoxA2 during cholestatic liver injury. Messenger RNA expression in SMCCs and LGCCs was assessed by polymerase chain reaction (PCR) array analysis. Liver tissues and hepatic stellate cells (HSCs) from primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) patients were tested by real-time PCR for methylation, senescence, and fibrosis markers. Bile duct ligation (BDL) and multidrug resistance protein 2 (MDR2) knockout mice (MDR2-/- ) were used as animal models of cholestatic liver injury with or without healthy transplanted large or small cholangiocytes. We demonstrated that FoxA2 was notably enhanced in murine liver progenitor cells and SMCCs and was silenced in human PSC and PBC liver tissues relative to respective controls that are correlated with the epigenetic methylation enzymes, DNA methyltransferase (DNMT) 1 and DNMT3B. Serum alanine aminotransferase and aspartate aminotransferase levels in nonobese diabetic/severe combined immunodeficiency mice engrafted with SMCCs post-BDL showed significant changes compared to vehicle-treated mice, along with improved liver fibrosis. Enhanced expression of FoxA2 was observed in BDL mouse liver after SMCC cell therapy. Furthermore, activation of fibrosis signaling pathways were observed in BDL/MDR2-/- mouse liver as well as in isolated HSCs by laser capture microdissection, and these signals were recovered along with reduced hepatic senescence and enhanced hepatic stellate cellular senescence after SMCC engraft
Berlino : una nuova composizione urbana per l'area dell'ospedale universitario Charité
No full textLAUREA MAGISTRALEBerlino, la città, è il punto di partenza, l’incipit del pensiero progettuale.
Marc Augé definiva la città come “un cantiere” in cui tutto si trasforma cancellando, ogni giorno, la memoria del giorno precedente, e in questa perenne trasformazione è riposta ogni speranza per un futuro imprevedibile e quindi inconoscibile. Il passato è semplicemente rimosso, come rimossa è la necessità di definire, in senso proprio, cioè come proiezione del passato in un futuro attendibile, un progetto.
Berlino si presenta come un cantiere, una città frammentata che cerca con fatica una forma riconoscibile, una città storica stratificata e incompleta.
La città dell’avanguardia sembra essersi arresa alla consolatoria poetica del frammento, accettando il rapporto tra la crisi della vita sociale e la frammentazione dello spazio urbano, relegandosi al solo linguaggio. Davanti a questo fallimento dell’architettura moderna nella costruzione della città l’obiettivo del progetto è stata la ricerca di un principio d’ordine, di una trama, per provare a riconoscere un disegno più generale, di delineare una reale alternativa alle forme della città.
L’approfondimento critico della storia di Berlino ha permesso di ristabilire un comprensibile sistema di nessi sintattici tra i fatti che costruiscono i luoghi dell’abitare, di riconoscere i segni e le trame sottese del territorio, seguendoli con il progetto che, a questo punto, tende alla ricomposizione della città.
L’area di progetto del Charité è stata l’occasione per proporre una tesi per la città di Berlino. Lo studio preciso dei tracciati storici ha portato a una conoscenza esatta della regola insita nel costruito, mostrando anche tuttavia il contrasto, l’interruzione che porta a un dialogo e a un confronto obbligato fra i personaggi della città. Il progetto per il centro di ricerca non deve essere considerato come un ampliamento di un brano della città ma come una costruzione o meglio ridefinizione della città esistente.
Aldo Rossi affermava che solo attraverso il progetto è possibile rendere manifesti e comprensibili i fatti costruiti: solo con un ipotesi è possibile capire quale sarà la dinamica della città del futuro, come si comporteranno i fatti urbani presi in causa, quali saranno i vincoli e i problemi da affrontare. Il progetto del Charité non vuole risolvere una situazione emarginata stretta dai vincoli che l’hanno resa un brano di territorio snaturato dal corpus della città, ma una nuova visione (o composizione) urbana, un nuovo rapporto tra architettura e costruito, rafforzandosi a vicenda con architetture riconoscibili: un disegno di corti crea un sistema di pieni e vuoti culminanti con il parco che dall’edificio storico della Charité si affaccia sul fiume
Amelioration of Ductular Reaction by Stem Cell Derived Extracellular Vesicles in MDR2 Knockout Mice via Lethal‐7 microRNA
No full textCholangiopathies are diseases that affect cholangiocytes, the cells lining the biliary tract. Liver stem cells (LSCs) are able to differentiate into all cells of the liver and possibly influence the surrounding liver tissue by secretion of signaling molecules. One way in which cells can interact is through secretion of extracellular vesicles (EVs), which are small membrane-bound vesicles that contain proteins, microRNAs (miRNAs), and cytokines. We evaluated the contents of liver stem cell-derived EVs (LSCEVs), compared their miRNA contents to those of EVs isolated from hepatocytes, and evaluated the downstream targets of these miRNAs. We finally evaluated the crosstalk among LSCs, cholangiocytes, and human hepatic stellate cells (HSCs). We showed that LSCEVs were able to reduce ductular reaction and biliary fibrosis in multidrug resistance protein 2 (MDR2)(-/-) mice. Additionally, we showed that cholangiocyte growth was reduced and HSCs were deactivated in LSCEV-treated mice. Evaluation of LSCEV contents compared with EVs derived from hepatocytes showed a large increase in the miRNA, lethal-7 (let-7). Further evaluation of let-7 in MDR2(-/-) mice and human primary sclerosing cholangitis samples showed reduced levels of let-7 compared with controls. In liver tissues and isolated cholangiocytes, downstream targets of let-7 (identified by ingenuity pathway analysis), Lin28a (Lin28 homolog A), Lin28b (Lin28 homolog B), IL-13 (interleukin 13), NR1H4 (nuclear receptor subfamily 1 group H member 4) and NF-kappa B (nuclear factor kappa B), are elevated in MDR2(-/-) mice, but treatment with LSCEVs reduced levels of these mediators of ductular reaction and biliary fibrosis through the inhibition of NF-kappa B and IL-13 signaling pathways. Evaluation of crosstalk using cholangiocyte supernatants from LSCEV-treated cells on cultured HSCs showed that HSCs had reduced levels of fibrosis and increased senescence. Conclusion: Our studies indicate that LSCEVs could be a possible treatment for cholangiopathies or could be used for target validation for future therapies
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