Underground Paris: the dark side of the city of light

71 σ.Ο υπόγειος κόσμος του Παρισιού, οι κατακόμβες, οι υπόνομοι, τα εγκαταλελειμμένα λατομεία, είναι ένας κόσμος που δημιουργήθηκε με σκοπό να εξυπηρετήσει τις ανάγκες της υπέργειας πόλης και συγχρόνως να κρύψει την εξαθλίωση των φτωχών. Ένας κόσμος που λόγω των συνθηκών διαβίωσης της λαμπρής αστικής κοινωνίας, αναγκάστηκε να παραλάβει τις ζωές ανθρώπων που ζούσαν στο περιθώριο. Ο σκοτεινός κόσμος που παράλληλα με τη μιζέρια και το παρακμιακό του πρόσωπο, είχε πρωταρχικό ρόλο στη βελτίωση της ποιότητας ζωής της πόλης. Ο υπόγειος χώρος περιγράφεται και αναλύεται, μαζί με τις κοινωνικές και πολιτικές εξελίξεις που έπαιξαν σημαντικό ρόλο στη διαμόρφωσή του, προκειμένου να αποδειχτεί η άρρηκτη σχέση των δύο κόσμων, αλλά και η σημασία του υπόγειου κόσμου για την επιβίωση του υπέργειου. Τελικά, το «φώς» και το «σκοτάδι» είναι οι δύο όψεις του Παρισιού, που ενώ συνυπάρχουν και αλληλοεξαρτώνται, προσποιούνται άγνοια η μία για την ύπαρξη της άλλης.The underground world of Paris, the Catacombs, the sewers and the abandoned quarries consist a world that was created in order to serve the needs of the city above, and to hide the poverty of the poor class. It is a world that, due to the living conditions of the high class society, was forced to absorb the lives of people living on the margins. This dark world, who alongside the misery and its decadence face, was the main reason of improvement in citizens’ lives. The underground area is described and analyzed, along with the social and political developments that played an important role in shaping it, in order to demonstrate the inextricable bond between the two worlds, and also the importance of the underground world for survival of the city above. Eventually, "light" and "darkness" are two sides of Paris, which whilst coexisting and being interdependent, pretend ignorance one for the existence of the other

Restriction of extracellular lipids renders pancreatic cancer dependent on autophagy.

BACKGROUND KRAS is the predominant oncogene mutated in pancreatic ductal adenocarcinoma (PDAC), the fourth cause of cancer-related deaths worldwide. Mutant KRAS-driven tumors are metabolically programmed to support their growth and survival, which can be used to identify metabolic vulnerabilities. In the present study, we aimed to understand the role of extracellularly derived fatty acids in KRAS-driven pancreatic cancer. METHODS To assess the dependence of PDAC cells on extracellular fatty acids we employed delipidated serum or RNAi-mediated suppression of ACSL3 (to inhibit the activation and cellular retention of extracellular fatty acids) followed by cell proliferation assays, qPCR, apoptosis assays, immunoblots and fluorescence microscopy experiments. To assess autophagy in vivo, we employed the KrasG12D/+;p53flox/flox;Pdx1-CreERT2 (KPC) mice crossed with Acsl3 knockout mice, and to assess the efficacy of the combination therapy of ACSL3 and autophagy inhibition we used xenografted human cancer cell-derived tumors in immunocompromised mice. RESULTS Here we show that depletion of extracellularly derived lipids either by serum lipid restriction or suppression of ACSL3, triggers autophagy, a process that protects PDAC cells from the reduction of bioenergetic intermediates. Combined extracellular lipid deprivation and autophagy inhibition exhibits anti-proliferative and pro-apoptotic effects against PDAC cell lines in vitro and promotes suppression of xenografted human pancreatic cancer cell-derived tumors in mice. Therefore, we propose lipid deprivation and autophagy blockade as a potential co-targeting strategy for PDAC treatment. CONCLUSIONS Our work unravels a central role of extracellular lipid supply in ensuring fatty acid provision in cancer cells, unmasking a previously unappreciated metabolic vulnerability of PDAC cells

Altered Distribution and Expression of Syndecan-1 and -4 as an Additional Hallmark in Psoriasis

Syndecans act as independent co-receptors to exert biological activities and their altered function is associated with many pathophysiological conditions. Here, syndecan-1 and -4 were examined in lesional skin of patients with psoriasis. Immunohistochemical staining confirmed altered syndecan-1 distribution and revealed absence of syndecan-4 expression in the epidermis. Fibronectin (FN)—known to influence inflammation and keratinocyte hyperproliferation via α5β1 integrin in psoriasis—was also decreased. Syndecan-1 and -4 expression was analyzed in freshly isolated lesional psoriatic human keratinocytes (PHK) characterized based on their proliferation and differentiation properties. mRNA levels of syndecan-1 were similar between healthy and PHK, while syndecan-4 was significantly decreased. Cell growth and release of the pro-inflammatory Tumor Necrosis Factor-alpha (TNFα) were selectively and significantly induced in PHKs plated on FN. Results from co-culture of healthy keratinocytes and psoriatic fibroblasts led to the speculation that at least one factor released by fibroblasts down-regulate syndecan-1 expression in PHK plated on FN. To assay if biological treatments for psoriasis target keratinocyte proliferation, gelatin-based patches enriched with inteleukin (IL)-17α or TNFα blockers were prepared and tested using a full-thickness healthy epidermal model (Phenion®). Immunohistochemistry analysis showed that both blockers impacted the localisation of syndecan-1 within the refined epidermis. These results provide evidence that syndecans expression are modified in psoriasis, suggesting that they may represent markers of interest in this pathology

Levels of Produced Antibodies after Vaccination with mRNA Vaccine; Effect of Previous Infection with SARS-CoV-2

The aim of this study was to estimate the immunogenic effect of mRNA vaccine against SARS-CoV-2. This study included 510 participants who received mRNA vaccine. The measurement of anti-COVID-19 antibodies was performed using the Abbott SARS-CoV-2 IgG quantitative assay (Abbott). Overall, mean titer of anti-Spike antibodies was 19,319.2 ± 1787.5 AU/mL. Vaccination induced a robust immunogenic response in those previously infected with SARS-CoV-2 compared with non-infected subjects. Additionally, individuals that were asymptomatic after vaccination produced lower levels of antibodies compared to feverish individuals. In conclusion, remarkably high levels of anti-Spike COVID-19 antibodies were observed after vaccination

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit