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The mechanism, the effectiveness, and the potential damage during limewash removal from wall painting models were evaluated for agar gels and water-based pads constituted by ArbocelTM BWW 40 cellulosic fibre. Cleaning materials in different formulations were compared: pure and with additives (ethylenediaminetetraacetic acid, EDTA, and ammonium citrate tribasic, TAC) in different percentages (2% and 3%). The cleaning action was evaluated on laboratory model samples, prepared with hematite a fresco and an egg-based tempera with limewash overlayers. Calcium and iron extracted by cleaning materials were quantified by inductively coupled plasma-mass spectrometry (ICP-MS). The potential damage to the hematite painting layers was also studied by electron paramagnetic resonance (EPR) spectroscopy. A visual observation of the limewash detachment induced by the overall cleaning was also performed. Results suggest that limewash removal mainly occurs by aqueous solution release from the cleaning system, with subsequent layer wetting, probable layer swelling, weakening and complete or partial detachment. A stronger limewash adhesion on the hydrophilic fresco surface than on tempera, was observed. None of the used cleaning materials resulted harmful to the integrity of the hematite layer underneath the limewash. A small damage in terms of extracted iron was detected in the cleaning systems after direct contact with fresco and tempera hematite layers; a “protective” effect by the tempera layer was observed for the pigment, due to the organic binder and triggered by the hydrophobic content of the egg-based medium. Cleaning materials with additives are more harmful than pure materials, with a greater coordinating ability for EDTA than for TAC, which increases with chelator percentage. Data suggest a more efficient backward transportation of aqueous solutions containing calcium and iron ions towards gels with respect to cellulose, due to their smallest pore size. All these results lead to operative suggestions: for fresco painting layers, pure gel allows both a good limewash removal and a lack of damage on the hematite layers. Instead, for tempera layers a good limewash removal and a negligible damage on the pigment was shown by gel, both pure and additivated with TAC, and pure cellulose. Therefore, the present study allows to identify proper characterization methods for evaluating effectiveness and damage in limewash removal and to give useful suggestions for the planning of repeated cleaning operations on a real polychrome object.

Background The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hypothesis that SGLT2-I have anti-inflammatory effects along with glucose-lowering properties. Therefore, we investigated the link between stress hyperglycemia, inflammatory burden, and infarct size in a cohort of type 2 diabetic patients presenting with AMI treated with SGLT2-I versus other oral anti-diabetic (OAD) agents. Methods In this multicenter international observational registry, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the presence of anti-diabetic therapy at the admission, patients were divided into those receiving SGLT2-I (SGLT-I users) versus other OAD agents (non-SGLT2-I users). The following inflammatory markers were evaluated at different time points: white-blood-cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), and C-reactive protein. Infarct size was assessed by echocardiography and by peak troponin levels. Results The study population consisted of 583 AMI patients (with or without ST-segment elevation): 98 SGLT2-I users and 485 non-SGLT-I users. Hyperglycemia at admission was less prevalent in the SGLT2-I group. Smaller infarct size was observed in patients treated with SGLT2-I compared to non-SGLT2-I group. On admission and at 24 h, inflammatory indices were significantly higher in non-SGLT2-I users compared to SGLT2-I patients, with a significant increase in neutrophil levels at 24 h. At multivariable analysis, the use of SGLT2-I was a significant predictor of reduced inflammatory response (OR 0.457, 95% CI 0.275–0.758, p = 0.002), independently of age, admission creatinine values, and admission glycemia. Conversely, peak troponin values and NSTEMI occurrence were independent predictors of a higher inflammatory status. Conclusions Type 2 diabetic AMI patients receiving SGLT2-I exhibited significantly reduced inflammatory response and smaller infarct size compared to those receiving other OAD agents, independently of glucose-metabolic control. Our findings are hypothesis generating and provide new insights on the cardioprotective effects of SGLT2-I in the setting of coronary artery disease. Trial Registration: Data are part of the ongoing observational registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT 05261867.

Background. Diabetic patients presenting with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) have an increased risk of contrast-induced-acute kidney injury (CI-AKI). It has been shown that sodium-glucose cotransporter-2 inhibitors (SGLT2-I) have a nephroprotective effect. Purpose. To analyze the association between chronic SGLT2-I treatment and the development of CI-AKI in diabetic patients with AMI (both ST- and non-ST segment elevation myocardial infarction) treated with PCI, in both patients with and without chronic kidney disease (CKD). Methods. In this multicenter international registry, consecutive patients with type 2 diabetes mellitus (T2DM) and AMI undergoing PCI between 2018 and 2021 were enrolled. The study population was stratified by the presence of CKD and anti-diabetic therapy at admission (SGLT2-I versus non-SGLT2-I users). CI-AKI was defined as an absolute (≥0.5 mg/dl) or relative increase (≥25%) in creatinine at 48-72 h after PCI compared to baseline values. Results. The study population consisted of 646 AMI patients: 111 SGLT2-I users [28 (25.2%) with CKD] and 535 non-SGLT2-I users [221 (41.3%) with CKD]. The median age was 70 [61-79] years, and more than 77% were males. Independently of creatinine at admission, SGLT2-I users exhibited significantly lower creatinine values at 72h after PCI, both in the non-CKD and CKD stratum. After PCI, the overall rate of CI-AKI was 76 (11.8%), significantly lower in SGLT2-I users compared to non-SGLT2-I patients (5.4% vs 13.1%, p=0.022). This finding was confirmed also in patients without CKD (p=0.040). In the CKD cohort, SGLT2-I users maintained significantly lower creatinine values at discharge, albeit without significant differences in CI-AKI rate compared to non-SGLT2-I patients. At multivariate analysis, the use of SGLT2-I was identified as an independent predictor of reduced rate of CI-AKI (OR 0.356; 95%CI 0.134-0.943, p=0.038). Patients with CI-AKI reported a longer hospital stay and higher incidence of adverse cardiovascular events at follow-up (p=0.001), mostly in the CKD cohort. Conclusion. In T2DM patients with AMI, the use of SGLT2-I was associated with a lower risk of CI-AKI during the index hospitalization, mostly in patients without CKD. Our results provide new insights into the cardio and nephroprotective effects of SGLT2-I in the setting of AMI. Trial Registration: data are part of the observational Registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT 05261867.

The cellular heterogeneity within a variety of solid tumors is influenced by several type of tumor-associated bacteria through yet poorly understood mechanisms. Unbiased genomic analysis revealed that right-sided colorectal tumors with poorer prognosis are preferentially populated with species related toEscherichia coli, including strains that are producing colibactin. By applying metabolomic profilingin situ, the presence of colibactin-producingEscherichia coli(CoPEC) was identified to establish a high-glycerophospholipid microenvironment within right-sided colorectal tumors that are bearing mutations in either APC or KRAS. Using spatial approaches, we revealed that bacterial microniches are poorly infiltrated with CD8+T cells. The aforementioned alterations in lipid metabolism negatively correlated with immunomodulatory and neurotrophic factors among which the human regenerating family member 3 alpha gene (REG3A). Accordingly, the loss of its ortholog enhances growth at the proximal colon of tumors with a microenvironment that impedes immune surveillance and shares similarities to human right-sided colorectal tumors. This work clarifies how the presence of colibactin-producing bacteria may locally establish tumor heterogeneity for lipid metabolism to promote cancer progression and provide unique insights both for therapeutic intervention and enabling basic research into the mechanisms of microbiota-host interaction.STATEMENT OF SIGNIFICANCEApplyingin situmetabolic imaging to patients’ tumors revealed that the accumulation of colibactin-producing bacteria that locally creates a potential vulnerability to cancer treatments through lipid metabolic reprogramming of tumor cells.

Streptococcus gallolyticus subsp. gallolyticus (SGG), an opportunistic gram-positive pathogen responsible for septicemia and endocarditis in the elderly, is often associated with colon cancer (CRC). In this work, we investigated the oncogenic role ofSGGstrain UCN34 using the azoxymethane (AOM)-induced CRC modelin vivo, organoid formationex vivoand proteomic and phosphoproteomic analyses from murine colons. We showed thatSGGUCN34 accelerates colon tumor development in the murine CRC model. Full proteome and phosphoproteome analysis of murine colons chronically colonized bySGGUCN34 or the closely related non-pathogenicS. gallolyticus subsp. macedonicus(SGM) revealed that 164 proteins and 725 phosphorylation sites were differentially regulated following colonization bySGGUCN34. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced following colonization bySGGUCN34, as most proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed significantly elevated activities in several cancer hallmark pathways affecting tumoral cells and their microenvironment, i.e. MAPK (ERK, JNK and p38), mTOR and integrin/ILK/actin signaling, inSGGUCN34 colonized colon. Importantly, analysis of protein arrays of human colon tumors colonized withSGGshowed up-regulation of PI3K/Akt/mTOR and MAPK pathways, providing clinical relevance to our findings. To testSGG’s capacity to induce pre-cancerous transformation of the murine colonic epithelium, we grewex vivoorganoids which revealed unusual structures with compact morphology following exposure toSGG. Taken together, our results reveal that the oncogenic role ofSGGUCN34 is associated with activation of multiple cancer-related signaling pathways.Author SummaryColorectal cancer is the third most common cause of cancer mortality worldwide. The colon is a very singular organ, colonized by a vast and complex community of microorganisms, known as the gut microbiota. Strong evidence supports a role of the microbiota in colon cancer development.Streptococcus gallolyticussubsp.gallolyticus(SGG), a gut commensal, was one of the first bacteria to be associated with colorectal cancer. A better understanding of the role ofSGGin colon cancer development is critical to developing novel strategies to improve clinical diagnosis and treatment of this disease. Here, using a global proteomic analysis of mouse colonic tissue colonized bySGG, we show that over 90% of the proteins with altered levels are involved in cancer.SGGcolonization promotes autocrine and paracrine pro-tumor signals contributing to transformation of the colonic epithelium but also modifying the stromal microenvironment, which in turn sustains tumor development. Importantly, two tumor hallmark pathways (PI3K/Akt/mTOR and MAPK) identified in our mouse model were also found in human colon tumor biopsies colonized bySGG, strengthening the clinical relevance to our study.

Monitoring the actual conditions of critical infrastructure assets is a priority for administrators to guarantee high-standard in terms of structural stability, and operational safety and to prevent damages and deterioration. Nowadays, most protocols for assessing road pavement conditions, including viaducts and bridges, are based on visual inspections conducted by specialized operators and, rarely, the local application of ground-based technologies such as IoT Wireless Sensors, laser scanners, Falling Weight Deflectometers, and accelerometers. However, the high costs of maintenance operations and on-site surveys, which involves the partial or total temporary closure of the infrastructure for the duration of the tests, still limit the implementation of these procedures at the network-scale level. Accordingly, the definition of innovative, automatic, and low-cost procedures for continuous monitoring operations, especially for road pavements and concrete bridges, is still an open challenge. In this context, recent developments in Artificial Neural Networks (ANNs) have opened new possibilities in the automatic recognition and geo-localization of damages affecting critical transportation assets, such as bridges and viaducts. This research presents an experimental application for the automatic detection of deteriorated bridge-deck expansion joints and the classification of pavement distresses based on Artificial Neural Networks models. More specifically, the methodology is founded on the latest generation of ANNs algorithms, among which "YOLO v5". For this purpose, an experimental evaluation is conducted by the acquisition of a large dataset of imageries of road damages and bridge-deck joints, collected by open-source datasets, and the processing by ANNs. Furthermore, a field experiment was conducted in order to collect several videos of bridges, selected as case-studies, by means of an instrumented vehicle, through a High-Definition resolution camera. The acquired images were post-processed and implemented for the training phases of the ANNs and the verification phases of the developed model. The application of the presented approach provides a reliable, affordable, and promising methodology for the automatic identification and localization of pavement distresses and bridge-deck joints damages, to be rapidly managed and decisively actioned by administrative authorities and asset owners, giving crucial information that could be implemented for the prioritisation of maintenance activities within Asset Management Systems. The findings of this study demonstrate that ANNs approaches and Deep Learning algorithms, can be applied to complement Non-Destructive Remote Sensing technologies (e.g., satellite radar interferometry, Laser Scanners), localizing automatically the pavement and infrastructure damages, paving the way for integrated approaches in the smart monitoring of infrastructure assets.

International audience; Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.

The synthesis of hydrogels that are based on poly-hydroxyethyl methacrylate, p(HEMA), network semi-interpenetrated with linear polyvinylpyrrolidone (PVP) was optimized in order to allow both a fast preparation and a high cleaning effectiveness of artistic surfaces. For this purpose, the synthesis parameters of the gel with PVP having a high molecular weight (1300 kDa) that were reported in the literature, were modified in terms of temperature, time, and crosslinker amount. In addition, the gel composition was modified by using PVP with different molecular weights, by changing the initiator and by adding maleic anhydride. The modified gels were characterized in terms of equilibrium water content (EWC), water uptake, conversion grade, and thermal properties by differential scanning calorimetry (DSC). The cleaning effectiveness of the gels was studied through the removal of copper salts from laboratory-stained specimens. Cleaning materials were characterized by electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, and inductively-coupled plasma-mass spectrometry (ICP-MS). Cleaning was assessed on marble specimens by color variation measurements. The gel synthesis is accelerated by using PVP 360 kDa. The addition of maleic anhydride in the p(HEMA)/PVP network allows the most effective removal of copper salt deposits from marble since it acts as a chelator towards copper ions.

BackgroundSodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type 2 diabetes mellitus (T2DM). They have also gained interest for their potential anti-arrhythmic role and their ability to reduce the occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs) in T2DM and heart failure patients.ObjectivesTo investigate in-hospital new-onset cardiac arrhythmias in a cohort of T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-i vs. other oral anti-diabetic agents (non-SGLT2-i users).MethodsPatients from the SGLT2-I AMI PROTECT registry (NCT05261867) were stratified according to the use of SGLT2-i before admission for AMI, divided into SGLT2-i users vs. non-SGLT2-i users. In-hospital outcomes included the occurrence of in-hospital new-onset cardiac arrhythmias (NOCAs), defined as a composite of new-onset AF and sustained new-onset ventricular tachycardia (VT) and/or ventricular fibrillation (VF) during hospitalization.ResultsThe study population comprised 646 AMI patients categorized into SGLT2-i users (111 patients) and non-SGLT2-i users (535 patients). SGLT2-i users had a lower rate of NOCAs compared with non-SGLT2-i users (6.3 vs. 15.7%, p = 0.010). Moreover, SGLT2-i was associated with a lower rate of AF and VT/VF considered individually (p = 0.032). In the multivariate logistic regression model, after adjusting for all confounding factors, the use of SGLT2-i was identified as an independent predictor of the lower occurrence of NOCAs (OR = 0.35; 95%CI 0.14–0.86; p = 0.022). At multinomial logistic regression, after adjusting for potential confounders, SGLT2-i therapy remained an independent predictor of VT/VF occurrence (OR = 0.20; 95%CI 0.04–0.97; p = 0.046) but not of AF occurrence.ConclusionsIn T2DM patients, the use of SGLT2-i was associated with a lower risk of new-onset arrhythmic events during hospitalization for AMI. In particular, the primary effect was expressed in the reduction of VAs. These findings emphasize the cardioprotective effects of SGLT2-i in the setting of AMI beyond glycemic control.Trial registrationData are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov, identifier: NCT05261867.

Aims: To investigate in-hospital and long-term prognosis in T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-I versus other oral anti-diabetic agents (non-SGLT2-I users). Methods: In this multicenter international registry all consecutive diabetic AMI patients undergoing percutaneous coronary intervention between 2018 and 2021 were enrolled and, based on the admission anti-diabetic therapy, divided into SGLT-I users versus non-SGLT2-I users. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE). Secondary outcomes included i) in-hospital cardiovascular death, recurrent AMI, occurrence of arrhythmias, and contrast-induced acute kidney injury (CI-AKI); ii) long-term cardiovascular mortality, recurrent AMI, heart failure (HF) hospitalization. Results: The study population consisted of 646 AMI patients (with or without ST-segment elevation): 111 SGLT2-I users and 535 non-SGLT-I users. The use of SGLT2-I was associated with a significantly lower in-hospital cardiovascular death, arrhythmic burden, and occurrence of CI-AKI (all p < 0.05). During a median follow-up of 24 ± 13 months, the primary composite endpoint, as well as cardiovascular mortality and HF hospitalization were lower for SGLT2-I users compared to non-SGLT2-I patients (p < 0.04 for all). After adjusting for confounding factors, the use of SGLT2-I was identified as independent predictor of reduced MACE occurrence (HR=0.57; 95%CI:0.33–0.99; p = 0.039) and HF hospitalization (HR=0.46; 95%CI:0.21–0.98; p = 0.041). Conclusions: In T2DM AMI patients, the use of SGLT2-I was associated with a lower risk of adverse cardiovascular outcomes during index hospitalization and long-term follow-up. Our findings provide new insights into the cardioprotective effects of SGLT2-I in the setting of AMI. Registration: Data are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT05261867.