Implication of Cellular Senescence in Osteoarthritis: A Study on Equine Synovial Fluid Mesenchymal Stromal Cells

: Osteoarthritis (OA) is described as a chronic degenerative disease characterized by the loss of articular cartilage. Senescence is a natural cellular response to stressors. Beneficial in certain conditions, the accumulation of senescent cells has been implicated in the pathophysiology of many diseases associated with aging. Recently, it has been demonstrated that mesenchymal stem/stromal cells isolated from OA patients contain many senescent cells that inhibit cartilage regeneration. However, the link between cellular senescence in MSCs and OA progression is still debated. In this study, we aim to characterize and compare synovial fluid MSCs (sf-MSCs), isolated from OA joints, with healthy sf-MSCs, investigating the senescence hallmarks and how this state could affect cartilage repair. Sf-MSCs were isolated from tibiotarsal joints of healthy and diseased horses with an established diagnosis of OA with an age ranging from 8 to 14 years. Cells were cultured in vitro and characterized for cell proliferation assay, cell cycle analysis, ROS detection assay, ultrastructure analysis, and the expression of senescent markers. To evaluate the influence of senescence on chondrogenic differentiation, OA sf-MSCs were stimulated in vitro for up to 21 days with chondrogenic factors, and the expression of chondrogenic markers was compared with healthy sf-MSCs. Our findings demonstrated the presence of senescent sf-MSCs in OA joints with impaired chondrogenic differentiation abilities, which could have a potential influence on OA progression

A deep-learning model to continuously predict severe acute kidney injury based on urine output changes in critically ill patients

BACKGROUND: Acute Kidney Injury (AKI), a frequentcomplication of pateints in theIntensive Care Unit (ICU), is associated with a high mortality rate. Early prediction of AKI is essential in order to trigger the use of preventive careactions.METHODS: The aim of this study was to ascertain the accuracy of two mathematical analysis models in obtaining a predictive score for AKI development. A deep learning model based on a urine output trends was compared with a logistic regression analysis for AKI prediction in stages 2 and 3 (defined as the simultaneous increase of serum creatinine and decrease of urine output, according to the Acute Kidney Injury Network (AKIN) guidelines). Two retrospective datasets including 35,573 ICU patients were analyzed. Urine output data were used to train and test the logistic regression and the deep learning model.RESULTS: The deep learning model definedan area under the curve (AUC) of 0.89 (±0.01), sensitivity=0.8 and specificity=0.84, which was higher than the logistic regression analysis. The deep learning model was able to predict 88% of AKI cases more than 12h before their onset: for every 6 patients identified as being at risk of AKI by the deep learning model, 5 experienced the event. On the contrary, for every 12 patients not considered to be at risk by the model, 2 developed AKI.CONCLUSION: In conclusion, by using urine output trends, deep learning analysis was able to predict AKI episodes more than 12h in advance, and with a higher accuracy than the classical urine output thresholds. We suggest that this algorithm could be integrated inthe ICU setting to better manage, and potentially prevent, AKI episodes

Melanocortin-1 Receptor Positively Regulates Human Artery Endothelial Cell Migration.

Background/aims Melanocortin receptors (MCRs) belong to a hormonal signalling pathway with multiple homeostatic and protective actions. Microvascular and umbilical vein endothelial cells (ECs) express components of the melanocortin system, including the type 1 receptor (MC1R), playing a role in modulating inflammation and vascular tone. Since ECs exhibit a remarkable heterogeneity, we investigated whether human artery ECs express any functional MCR and whether its activation affects cell migration. Methods We used reverse transcription real-time PCR to examine the expression of melanocortin system components in primary human artery ECs. We assessed MC1R protein expression and activity by western blot, immunohistochemistry, cAMP production, and intracellular Ca²⁺ mobilization assays. We performed gap closure and scratch tests to examine cell migration after stimulation with alpha-melanocyte-stimulating hormone (α-MSH), the receptor highest-affinity natural ligand. We assessed differential time-dependent transcriptional changes in migrating cells by microarray analysis. Results We showed that human aortic ECs (HAoECs) express a functionally active MC1R. Unlike microvascular ECs, arterial cells did not express the α-MSH precursor proopiomelanocortin, nor produced the hormone. MC1R engagement with a single pulse of α-MSH accelerated HAoEC migration both in the directional migration assay and in the scratch wound healing test. This was associated with an enhancement in Ca²⁺ signalling and inhibition of cAMP elevation. Time-course genome-wide expression analysis in HAoECs undergoing directional migration allowed identifying dynamic co-regulation of genes involved in extracellular matrix-receptor interaction, vesicle-mediated trafficking, and metal sensing - which have all well-established influences on EC motility -, without affecting the balance between pro- and anticoagulant genes. Conclusion Our work broadens the knowledge on peripherally expressed MC1R. These results indicate that the receptor is constitutively expressed by arterial ECs and provide evidence of a novel homeostatic function for MC1R, whose activation may participate in preventing/healing endothelial dysfunction or denudation in macrovascular arteries

Autoimmune polyglandular syndrome type 4: experience from a single reference center

Purpose: To characterize patients with APS type 4 among those affected by APS diagnosed and monitored at our local Reference Center for Autoimmune Polyglandular Syndromes. Methods: Monocentric observational retrospective study enrolling patients affected by APS diagnosed and monitored in a Reference Center. Clinical records were retrieved and analyzed. Results: 111 subjects (51 males) were affected by APS type 4, mean age at the onset was 23.1 ± 15.1 years. In 15 patients the diagnosis of APS was performed during the first clinical evaluation, in the other 96 after a latency of 11 years (range 1-46). The most frequent diseases were type I diabetes mellitus and celiac disease, equally distributed among sexes. Conclusions: The prevalence of APS type 4 is 9:100,000 people. Type I diabetes mellitus was the leading indicator of APS type 4 in 78% subjects and in 9% permitted the diagnosis occurring as second manifestation of the syndrome. Our data, showing that 50% of patients developed APS type 4 within the first ten years, don't suggest any particular follow-up time and, more importantly, don't specify any particular disease. It is important to emphasize that 5% of women developed premature ovarian failure

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Smart clothing n’ maxi-jewels

Da ogni crisi globale la moda ha tirato fuori il volto della sensibilità comune, portando alla luce le esigenze e i desideri di una società che, di volta in volta, ha dovuto ridefinire priorità e identità. In tal senso, l’emergenza COVID-19 ha generato un’evoluzione del rito della vestizione per cui non ci si veste più in base all’occasione ma in funzione di un’esigenza più generale di comfort e libertà di movimento: outdoor e indoor si fondono sulla scia dello smart working verso un altrettanto smart clothing che combina sportswear e abbigliamento formale. Sullo sfondo di questo abbigliamento passepartout che prescinde dal dress code, l’accessorio diventa protagonista indiscusso, un vero e proprio gioiello da esibire in formato maxi. L’attuale crisi economica ha visto crescere l’importanza dei gioielli d’alta gamma che nel 2020 hanno consolidato il proprio ruolo di beni-rifugio: i giacimenti di smeraldi, diamanti e rubini sono risorse esauribili, e proprio per la loro crescente rarità hanno rappresentato un ottimo investimento “di emergenza” nell’ultimo anno.After every global crisis, fashion has brought out the face of common sensibility, bringing to light the needs and desires of a society that, from time to time, has had to redefine its priorities and identity. In this sense, the COVID-19 emergency has generated an evolution in the ritual of dressing as we no longer dress according to the occasion but to a more general need for comfort and freedom of movement: outdoor and indoor merge in the wake of smart working towards a smart clothing that combines sportswear and formal wear. Against the backdrop of this passepartout clothing that is independent of the dress code, the accessory becomes the undisputed protagonist, a real jewel to be shown off in maxi format. The current economic crisis has seen an increase in the importance of high-end jewelry, which in 2020 has consolidated its role as a safe haven asset: the deposits of emeralds, diamonds and rubies are exhaustible resources, and precisely because of their increasing rarity they have represented an excellent “emergency” investment in the last year

C2C E ARTIGIANATO DIGITALE: MODA ETICA E PROCESSI PRODUTTIVI SOSTENIBILI

With the entry into the new geological epoch, the Anthropocene, we have seen how the world around us has transformed, and continues to change. Climate change and its consequences have triggered a new state of permanent emergency. This precarious state of equilibrium has prompted scholars in the field to find new solutions that can solve, at least in part, the problems that arise. By observing the natural world and through new design methodologies involving collaboration between applied sciences and design, we can develop intelligent solutions capable of restoring a natural order among the ecosystems of our planet.on l’ingresso nella nuova epoca geologica, l’Antropocene, abbiamo potuto osservare come il mondo che ci circonda si sia trasformato, e continui a mutare. Il cambiamento climatico e le conseguenze ad esso connesso hanno innescato un nuovo stato di emergenza permanente. Questa condizione precaria di equilibrio ha spinto gli studiosi del settore a trovare nuove soluzioni in grado di risolvere, almeno in parte, i problemi che si presentano. Osservando il mondo naturale e attraverso nuove metodologie di progettazione, che implicano la collaborazione fra le scienze applicate e il design, possiamo sviluppare soluzioni intelligenti in grado ristabilire un ordine naturale fra gli ecosistemi del nostro pianeta. L’artigianato, insieme alle PMI, è il settore portante dell’economia italiana e ha permesso al Paese di resistere nei periodi di crisi. Proprio in risposta alla recente crisi economica e occupazionale, si è andata a creare una rete di digital makers che, grazie alle nuove tecnologie, sono stati in grado di crearsi un proprio business autonomo e sostenibile. Un’attività, questa, che ha dato nuovo respiro e nuova vita all’artigianato. Non a caso si parla di “Manufacturing Renaissance” e si fa strada la consapevolezza delle nuove possibilità che l’artigianato può offrire se ricontestualizzato alla luce delle nuove tecnologie