Unimolecular Variant of the Fluorescence Turn-On Oxidative Coupling of Catecholamines with Resorcinols

Reported herein is a unimolecular variant of the fluorescence turn-on oxidative coupling of catecholamines with resorcinols ("FluoResCat") based on the easily accessible conjugate 4-(2-((2,4-dihydroxybenzyl)amino)ethyl)benzene-1,2-diol (1). The process involves an alkali-activatable sequence of autoxidation and intramolecular cyclization steps with loss of carbon, leading to a fluorescent methanobenzofuroazocinone product identical to that obtained from the oxidative coupling of dopamine with resorcinol. A mechanistic route for this unexpected reaction, mimicking the synthesis of the natural fluorophore matlaline, would involve highly constrained polycyclic spiro intermediates (liquid chromatography–mass spectrometry analysis of intermediates, model reactions, and density functional theory calculations). Emission turn-on from 1 in response to oxygen, superoxide-generating systems, or gaseous ammonia/volatile amines may be of interest for sensing applications, for example, in smart packaging

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

Valorisation of municipal and tannery sludge via hydrothermal liquefaction: Effect of the substrate chemical composition on yield and quality of bio-crude

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Antioxidant activity of film forming systems based on melanins from 5,6-dihydroxyindole derivatives

The development of innovative dip-coating technologies for surface functionalization has been a very active issue over the past decade following the discovery of the adhesion properties of polydopamine, a eumelanin-like material. New opportunities have derived from the discovery that hexamethylenediamine (HMDA) markedly enhances film deposition from a variety of catechol, including the key eumelanin precursor 5,6-dihydroxyindole (DHI). The remarkable antioxidant properties of synthetic eumelanins from the other main melanogenic precursor 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and its methyl ester (MeDHICA) have recently been described. In this work the film forming properties of MeDHICA melanin generated in the presence of HMDA or other diamines/monoamines and the antioxidant activity of the resulting films were investigated. Further to a systematic investigation, the most promising results were obtained running the aerobic oxidative polymerization of MeDHICA in aqueous buffers at pH 9.0 at 1 mM in the presence HMDA at 1:1.5 molar ratio. Under these conditions a dark yellow pigment is formed over 24 h exhibiting good film forming properties on different supports. HPLC analysis of the film solubilized in organic solvents indicated a mixture of oligomers of MeDHICA up to hexamers. Further polymerization of the film was obtained by exposure to ammonia vapors. The films showed high antioxidant activities in the 2,2-diphenyl-1-picrylhydrazyl and Ferric Reducing Antioxidant Power assays. Biocompatibility of MeDHICA/HMDA films was assessed on HaCat cells

Muscle magnetic resonance imaging in myotonic dystrophy type 1 (DM1) : Refining muscle involvement and implications for clinical trials

Only a few studies have reported muscle imaging data on small cohorts of patients with myotonic dystrophy type 1 (DM1). We aimed to investigate the muscle involvement in a large cohort of patients in order to refine the pattern of muscle involvement, to better understand the pathophysiological mechanisms of muscle weakness, and to identify potential imaging biomarkers for disease activity and severity. One hundred and thirty-four DM1 patients underwent a cross-sectional muscle magnetic resonance imaging (MRI) study. Short tau inversion recovery (STIR) and T1 sequences in the lower and upper body were analyzed. Fat replacement, muscle atrophy and STIR positivity were evaluated using three different scales. Correlations between MRI scores, clinical features and genetic background were investigated. The most frequent pattern of muscle involvement in T1 consisted of fat replacement of the tongue, sternocleidomastoideus, paraspinalis, gluteus minimus, distal quadriceps and gastrocnemius medialis. Degree of fat replacement at MRI correlated with clinical severity and disease duration, but not with CTG expansion. Fat replacement was also detected in milder/asymptomatic patients. More than 80% of patients had STIR-positive signals in muscles. Most DM1 patients also showed a variable degree of muscle atrophy regardless of MRI signs of fat replacement. A subset of patients (20%) showed a 'marbled' muscle appearance. Muscle MRI is a sensitive biomarker of disease severity alsofor the milder spectrum of disease. STIR hyperintensity seems to precede fat replacement in T1. Beyond fat replacement, STIR positivity, muscle atrophy and a 'marbled' appearance suggest further mechanisms of muscle wasting and weakness in DM1, representing additional outcome measures and therapeutic targets for forthcoming clinical trials. We refined the pattern of muscle involvement in DM1 by upper and lower body muscle magnetic resonance imaging (MRI), identifying the most frequent pattern of fat replacement and confirming that muscle MRI is a sensitive biomarker of disease burden in DM1. We also observed: STIR-positive muscles in 80% of patients preceding fat replacement, muscle atrophy in muscles unreplaced by fat, and progeroid muscle appearance supporting a premature muscle senescence. Our findings provide novel insights into the pathophysiological mechanisms of muscle wasting and weakness in DM1, and could represent additional outcome measures and therapeutic targets for forthcoming clinical trials

Oxidant-dependent antioxidant activity of polydopamine films: The chemistry-morphology interplay

Polydopamine (PDA) films allow to functionalize almost all materials with a conformal and chemically active coating. These coatings can react with reducible metallic cations and with all kinds of molecules carrying nucleophilic groups. Recently, our team extended PDA chemistry to a vast repertoire of oxidants and to acidic conditions. However, the influence of changes in the method of PDA deposition on the properties of the obtained coatings, in particular the antioxidant properties, have not been sufficiently explored. It is anticipated that the antioxidant properties should depend on the film preparation method. A combination of experimental techniques, atomic force microscopy, cyclic voltammetry and X ray photoelectron spectroscopy are used to relate the antioxidant properties of PDA films to their structural features and to their chemical composition. It is demonstrated that the antioxidant properties of PDA films are not only dependent on the type of the employed oxidant – which can be expected to affect a variable density of oxidizable groups on the surface of PDA - but also on the oxidant film morphology and roughness

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

Nature-based solutions efficiency evaluation against natural hazards: modelling methods, advantages and limitations

Nature-based solutions (NBS) for hydro-meteorological risks (HMRs) reduction and management are becoming increasingly popular, but challenges such as the lack of well-recognised standard methodologies to evaluate their performance and upscale their implementation remain. We systematically evaluate the current state-of-the art on the models and tools that are utilised for the optimum allocation, design and efficiency evaluation of NBS for five HMRs (flooding, droughts, heatwaves, landslides, and storm surges and coastal erosion). We found that methods to assess the complex issue of NBS efficiency and cost-benefits analysis are still in the development stage and they have only been implemented through the methodologies developed for other purposes such as fluid dynamics models in micro and catchment scale contexts. Of the reviewed numerical models and tools MIKE-SHE, SWMM (for floods), ParFlow-TREES, ACRU, SIMGRO (for droughts), WRF, ENVI-met (for heatwaves), FUNWAVE-TVD, BROOK90 (for landslides), TELEMAC and ADCIRC (for storm surges) are more flexible to evaluate the performance and effectiveness of specific NBS such as wetlands, ponds, trees, parks, grass, green roof/walls, tree roots, vegetations, coral reefs, mangroves, sea grasses, oyster reefs, sea salt marshes, sandy beaches and dunes. We conclude that the models and tools that are capable of assessing the multiple benefits, particularly the performance and cost-effectiveness of NBS for HMR reduction and management are not readily available. Thus, our synthesis of modelling methods can facilitate their selection that can maximise opportunities and refute the current political hesitation of NBS deployment compared with grey solutions for HMR management but also for the provision of a wide range of social and economic co-benefits. However, there is still a need for bespoke modelling tools that can holistically assess the various components of NBS from an HMR reduction and management perspective. Such tools can facilitate impact assessment modelling under different NBS scenarios to build a solid evidence base for upscaling and replicating the implementation of NBS

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

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease