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Carlo Borromeo’s Instructions represent the only practical application of the Tridentine decrees in architecture. However, historians over time have given little weight to the work, which is mostly considered a simple parish handbook due to its practical-functional nature used to treat the sacred space. New research conducted on the literary work has focused on the massive diffusion of this treatise in the undergrowth of the ecclesiastical literature of the time, testifying to how much the Instructions are linked to the historical context and the spiritual needs of the post-Tridentine Church. The great novelty of the work lies in the fact that it completely overturned the way of writing about architecture. In the writings of Carlo Borromeo, a continuous interweaving between the doctrine of the soul and the sacred building is outlined to give the Church the image of an institution organically constituted in its material and spiritual reality. The influence of this work outside the Milanese context in which Carlo Borromeo worked is still to be clarified, especially in the South of Italy, which experienced the peak of its Counter-Reformation season between the seventeenth and eighteenth centuries. Here, Instructions will be analyzed along with the Antica Basilicografia of Pompeo Sarnelli (1686) and Il Rettore ecclesiastico of Marcello Cavalieri (1688), two writings born in the diocese of Benevento under the wing of the bishop Vincenzo Maria Orsini, a native of Gravina di Puglia.

This work reports preliminary results on the fluid dynamic simulation using ANSYS CFD software of a pilot scale reactor experimentally tested for the removal of VOCs (toluene, ethylbenzene, methyl ethyl ketone and xylenes). The reactor is constructed from the modification of a commercial air stripper and has been successfully evaluated for the removal of VOCs using Mn, Ce and Pt based catalysts on ceramic monoliths (bentonite). By means of ANSYS CFD simulation it was possible to represent the flow in the reactor (validating with experimental data) and to simulate the flow in the monolith channels. This information will allow us to have a better understanding of the fluid dynamics in the catalysts and to simulate the reactions with different VOCs by combining ANSYS CFD with ChemKin-PRO.

Whether incomplete functional revascularization has an impact on the clinical outcome of patients treated with transcatheter aortic valve implantation (TAVI) is still unknown. We aim to assess the prognostic value of residual functional SYNTAX score (rFSS) in a cohort of patients undergoing TAVI.One-hundred-twenty-four patients (229 lesions) with severe aortic stenosis and coronary artery disease (CAD) underwent fractional flow reserve (FFR)-guided revascularization. The primary endpoint of the study was the composite of cardiac death, myocardial infarction, and revascularization at the last available follow-up after TAVI. Median SYNTAX score (SS) and Functional SYNTAX score (FSS) at baseline were 7 (range 5-12) and 0 (range 0-7) respectively. After revascularization or deferral according to FFR, residual SS (rSS) and rFSS were 5 (range 0-8) and 0 (range 0-0) respectively. Angiographic incomplete revascularization (rSS0) was not associated with the primary endpoint (HR 1.2; 95% CI 0.4-3.9; p = 0.69), whereas functional incomplete revascularization (rFSS0) was associated with worse event-free survival at follow up after adjusting for clinical confounders (HR 3.7; 95% CI 1.0-13.7; p = 0.04).Incomplete functional revascularization is associated with adverse clinical outcomes after TAVI. Residual functional SYNTAX score may be regarded as a treatment goal for patients with CAD undergoing TAVI. Further studies are warranted to confirm our hypothesis.

The 20th century generated a crisis of public monuments. This paper proposes a reflection on the choices made by the society regarding what aspects of history to remember and how to provide a foundation for its collective identity. Since ancient times, the task of public monuments has been to imprint in history the perpetual memory of a character, identified as the ideal model around which the history of their time revolves. With the French Revolution, there was a fundamental change of course on this front. The public no longer needed to follow an ideal sovereign, and the story was no longer calibrated to a single character but to each citizen. The crisis of public monuments after World War II dealt with the concept of durability, a fundamental attribute for this archetype, with the consequent birth of the counter-monument. To fully understand this crisis, the evolution of one of the commemorative monuments par excellence — historiated column — will be analysed through three key examples, far apart in space and time, each exemplifying a precise evolutionary phase: Trajan’s Column, the Vendôme Column, and the Monument against Fascism, erected in 1986 by Esther Shalev-Gerz and Jochen Gerz.

Visual Studio Code is an extremely versatile development tool that can be customized and extended in many ways. In fact, you can customize its appearance, the code editor, and key shortcuts to make your editing experience extremely personalized.

Visual Studio Code is not just another evolved text editor with syntax colorization and automatic indentation. Instead, it is a very powerful code-focused development environment expressly designed to make it easier to write web, mobile, and cloud applications using languages that are available to different development platforms.

A 49-year-old man was referred to our cath-lab in 2015 after the detection of inducible ischaemia in the infero-lateral wall on single-photon emission CT performed due to a worsening stable angina. His cardiovascular risk factors accounted for family history of ischemic disease, high blood pressure and dyslipidaemia. The echocardiography highlighted a mildly reduced left ventricular function with infero-lateral wall hypokinesia. Coronary angiography revealed a chronic total occlusion (CTO) of the left circumflex artery (LCX) and a long diffuse severe disease of the right coronary artery (RCA). The left anterior descending artery (LAD) showed a diffuse atherosclerotic involvement without critical stenoses. Percutaneous coronary intervention (PCI) was performed after Heart Team discussion with implantation of two 3.5×28mm and 3.5×23mm Absorb bioresorbable vascular scaffold (BVS) on the RCA. Moreover, the LCX CTO was successfully treated by anterograde approach with implantation of a 3.0×28 mm Absorb BVS. Intravascular ultrasound confirmed the optimal result of both the interventions, while confirmed the long diffuse calcific involvement of the LAD with a thick cap calcific fibroatheroma at the virtual histology. The patient was discharged on dual antiplatelet therapy for twelve months. After five uneventful years, he was readmitted to our department for recurrence of worsening stable angina. At the coronary angiography a significant progression of the proximal LAD disease was noted. The lesion was judged hemodynamic relevant with pressure derived indices (instantaneous wave-free ratio 0.86; fractional flow reserve 0.70). The IVUS and optical coherence tomography (OCT) analysis confirmed the significant progression of the disease with a long, diffuse, sub-occlusive thick cap fibroatheroma stenosis (minimal lumen area 1.9 mm2; plaque burden 91%). The OCT analysis showed the complete resorption of the devices previously implanted to the RCA and the LCX, with optimal long-term results and positive remodelling in the LCX. Therefore, an OCT-guided PCI with marker-to-marker implantation of two 3.5×25 and 3×20 mm magnesium-based Magmaris BVS was performed. In 2022, the patient underwent an elective coronary angiography that demonstrated a complete resorption of both the Magmaris with an optimal OCT result. Conversely, the positive remodelled segment resulting from complete resorption of the poly-L-lactic-based BVS in the mid-LCX was shown to be progressed to a critical sub-occlusive fibroatheroma. A further OCT-guided PCI with deployment one 3.5×20mm Magmaris BVS was performed. Six months later, patient was asymptomatic with a good performance status. To the best of our knowledge, the present is the first case of multivessel repetitive imaging-based percutaneous revascularizations with the use of two different BVS technologies and a total of six devices implanted, with very long-term intracoronary imaging result. Through the paired intravascular imaging analysis, this case sought to provide insightful findings on vulnerable plaque atherosclerotic progression and on BVS biologic restoration therapy, a process that appears particularly appealing in young patients with advanced CAD, namely multivessel involvement and diffuse disease that still poses limitations to PCI.

Introduction Echocardiographic evaluation of severe aortic stenosis (SAS) is is important to guide the therapeutic approach but often challenging. Recent studies have demonstrated that the ratio of acceleration time/ejection time (AT/ET) is a simple and reproducible echocardiographic parameter that integrates aortic stenosis severity evaluation and adds information on patient's prognosis. Aim The aim of the study is to investigate the role of the ratio of acceleration time (AT) and ejection time (ET) and its major determinants in severe aortic stenosis . Methods Consecutive echocardiograms of patients with severe AS referred to our center were analyzed offline using Tomtec Arena (Tomtec, Untershlei heim, Germany). AT was measured from the start of the CW Doppler aortic wave, to the peak of the aortic jet. ET was calculated from the same starting point, to the end of the CW Doppler aortic wave. Results A total of 135 patients with severe aortic stenosis formed the study cohort: patients with AT/ET below the median value of 0.35 (vs. higher) presented lower LVEDV (60 vs. 71 ml/mq; p 0.014), left ventricle mass index (116 vs 130 g/m2; p 0.035) and higher LVEF (58 vs 50%; p 0.001), GLS (- 14 vs - 12%; p 0.025), FAC (46 vs 41%; p 0.01), SBP (141 vs 131 mmHg; p 0.003). At multivariable analysis the major AT/ET determinants were systolic arterial pressure and bi-ventricular performance parameters. The following nested regression were created: the first inclusive of systolic arterial pressure (PAS), fractional area change (FAC), left ventricular mass indexed (LVMI), global longitudinal strain (GLS) (R2=0.48 p Conclusion Our study demonstrated that AT/ET ratio relates quite well with LV performance in the context of SAS. An high ACT/ET ratio tends to be associated with a poor bi-ventricular performance and LV negative remodeling. It is possible that this simple parameter in the next future could help in staging the disease among SAS patients.

Background Right Ventricle/Pulmonary Artery (RV/PA) coupling has recently emerged as a relevant prognostic factor in patients undergoing transcatheter valvular interventions. The aim of this study is to assess the interaction between RV/PA coupling ratio and the incidence of Acute Kidney Injury (AKI) following TAVI in patients with severe aortic stenosis. Furthermore we investigated the interaction between this novel ratio and adverse events at 24 months follow-up. Methods A population of 283 patients was selected from the Verona Valvular Registry (CESC n =1918). RV/PA coupling was estimated as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PAPs) obtained through transthoracic echocardiograms. AKI was defined as an increase in serum creatinine (sCr) of at least 0.3 mg/dL up to 48 hours following TAVI. Major adverse cardiovascular events (MACEs) were defined as the composite occurrence of cardiac death, re-hospitalization for congestive heart failure and stroke. Results Mean age was 83.4 ± 5.36 years and 41.3% of patients were female. The median value of TAPSE/PAPs ratio was 0.5667 mm/mmHg and was used as a cut-off. A TAPSE/PASP ratio Furthermore, risk for 24 months MACEs was higher in the population with lower TAPSE/PAPs ratio (HR 2.672; CI 95% [1.195–5.974]; p = 0.017). Conclusion RV/PA coupling, as characterized by TAPSE/PAPs ratio, is a promising independent predictor of AKI, also associated with higher risk of major adverse cardiac events at follow-up in subjects undergoing TAVI. These data suggest a possible role for this novel index in risk stratification, assessment of the prognosis, and decision-making in these patients.

Summary Background Spinal muscular atrophy is a rare, autosomal recessive, neuromuscular disease caused by biallelic loss of the survival motor neuron 1 (SMN1) gene, resulting in motor neuron dysfunction. In this STR1VE-EU study, we aimed to evaluate the safety and efficacy of onasemnogene abeparvovec gene replacement therapy in infants with spinal muscular atrophy type 1, using broader eligibility criteria than those used in STR1VE-US. Methods STR1VE-EU was a multicentre, single-arm, single-dose, open-label phase 3 trial done at nine sites (hospitals and universities) in Italy (n=4), the UK (n=2), Belgium (n=2), and France (n=1). We enrolled patients younger than 6 months (180 days) with spinal muscular atrophy type 1 and the common biallelic pathogenic SMN1 exon 7–8 deletion or point mutations, and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 1014 vector genomes [vg]/kg). The outpatient follow-up consisted of assessments once per week starting at day 7 post-infusion for 4 weeks and then once per month until the end of the study (at age 18 months or early termination). The primary outcome was independent sitting for at least 10 s, as defined by the WHO Multicentre Growth Reference Study, at any visit up to the 18 months of age study visit, measured in the intention-to-treat population. Efficacy was compared with the Pediatric Neuromuscular Clinical Research (PNCR) natural history cohort. This trial is registered with ClinicalTrials.gov , NCT03461289 (completed). Findings From Aug 16, 2018, to Sept 11, 2020, 41 patients with spinal muscular atrophy were assessed for eligibility. The median age at onasemnogene abeparvovec dosing was 4·1 months (IQR 3·0–5·2). 32 (97%) of 33 patients completed the study and were included in the ITT population (one patient was excluded despite completing the study because of dosing at 181 days). 14 (44%, 97·5% CI 26–100) of 32 patients achieved the primary endpoint of functional independent sitting for at least 10 s at any visit up to the 18 months of age study visit (vs 0 of 23 untreated patients in the PNCR cohort; p Interpretation STR1VE-EU showed efficacy of onasemnogene abeparvovec in infants with symptomatic spinal muscular atrophy type 1. No new safety signals were identified, but further studies are needed to show long-term safety. The benefit–risk profile of onasemnogene abeparvovec seems favourable for this patient population, including those with severe disease at baseline. Funding Novartis Gene Therapies.

Increasing evidence suggests that during the COVID-19 pandemic, anxiety and depression during the perinatal period increased. The aim of the study is to estimate the prevalence of risk for both maternal depression and anxiety among women attending 18 healthcare centres in Italy during the SARS-COV-2 pandemic and to investigate the psychosocial risks and protective factors associated. It was divided into a retrospective phase (2019, 2020, and the first nine months of 2021) and a prospective phase (which began in November 2021 and it is still ongoing), which screened 12,479 and 2349 women, respectively, for a total of 14,828 women in the perinatal period. To evaluate the risk of anxiety and depression, the General Anxiety Disorder-7 (GAD-7), the Edinburgh Postnatal Depression Scale (EPDS), and an ad hoc form were used to collect sociodemographic variables. In the prospective study, the average age of the women is 31 (range 18–52) years. Results showed that the percentage of women who had EPDS score ≥9 increased from 11.6% in 2019 to 25.5% in the period ranging from November 2021 to April 2022. In logistic regression models, the variables associated with the risk of depression at a level ≤0.01 include having economic problems (OR 2.16) and not being able to rely on support from relatives or friends (OR 2.36). Having the professional status of the housewife is a lower risk (OR 0.52). Those associated with the risk of anxiety include being Italian (OR 2.97), having an education below secondary school level (OR 0.47), having some or many economic problems (OR 2.87), being unable to rely on support from relatives or friends (OR 2.48), and not having attended an antenatal course (OR 1.41). The data from this survey could be useful to determine the impact of the SARS-COV-2 pandemic on women and to establish a screening program with common and uniformly applied criteria which are consistent with national and international women’s mental health programs.

In this work, we developed a novel approach to purify [11C]Raclopride ([11C]RAC), an important positron emission tomography radiotracer, based on tailored shape-recognition polymers, with the aim to substitute single-pass HPLC purification with an in-flow trap & release process. Molecular imprinting technology (MIT) applied to solid phase extraction (MISPE) was investigated to develop a setting able to selectively extract [11C]RAC in a mixture containing a high amount of its precursor, (S)-O-Des-Methyl-Raclopride (DM-RAC). Two imprinted polymers selective for unlabeled RAC and DM-RAC were synthesized through a radical polymerization at 65 °C using methacrylic acid and trimethylolpropane trimethacrylate in the presence of template molecule (RAC or DM-RAC). The prepared polymer was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy and tested in MISPE experiments. The polymers were used in testing conditions, revealing a high retention capacity of RAC-MISPE to retain RAC either in the presence of similar concentrations of RAC and DM-RAC precursor (96.9%, RSD 6.6%) and in the presence of a large excess of precursor (90%, RSD 4.6%) in the loading solution. Starting from these promising results, preliminary studies for selective purification of [11C]Raclopride using this RAC-MISPE were performed and, while generally confirming the selectivity capacity of the polymer, revealed challenging applicability to the current synthetic process, mainly due to high backpressures and long elution times.

To determine the association between direct oral anticoagulant (DOAC) use and risk of major adverse cardiac events (MACEs) in patients with atrial fibrillation (AF).This study is a single-center prospective observational cohort study including 2366 outpatients with non-valvular AF on treatment with DOACs or vitamin K antagonists (VKAs) from February 2008 for patients on VKA and September 2013 for patients on novel oral anticoagulants. The primary endpoint was the incidence of MACE including fatal and non-fatal myocardial infarction (MI), cardiac revascularization, and cardiovascular death.The mean age was 75.1±9.0 years; 44.7% were women. During a mean follow-up of 33.3±21.9 months (6567 patients/years) 133 MACEs occurred (2.03%/year): 79 MI/cardiac revascularization and 54 cardiovascular deaths. Of these, 101 were on VKAs (2.42%/year) and 32 on DOACs (1.34%/year; log-rank test P=.040). This difference was evident also considering MI alone (1.53%/year and 0.63%/year in the VKA and DOAC group, respectively, log-rank test P=.009). At multivariable Cox proportional hazard regression analysis, use of DOACs was associated with a lower risk of MACE (hazard ratio, 0.636; 95% CI, 0.417 to 0.970; P=.036) and MI (hazard ratio, 0.497; 95% CI, 0.276 to 0.896; p=.020). Sensitivity analysis showed that this association was consistent in younger patients (75 years), in patients with anemia, and in those without chronic obstructive pulmonary disease and heart failure. We also found that both dabigatran and apixaban/rivaroxaban were associated with a lower rate of MACE, with similar efficacy between full and low doses.DOACs are associated with a lower risk of MACE in patients with AF independently from dosage.

Background Prosthetic Heart Valves are always more frequent in the clinical practice. Particularly, sometimes more than one native valve is affected and needs to be surgically treated. On the other side, replaced prosthesis could also degenerate over time, leading to worsening symptomatic heart failure. There are no many cases of combined percutaneous approach to both aortic and mitral prosthetic valve deterioration: our aim is to display a case of this complex clinical setting. Case: A 76–year–old man with previous surgical mitral and aortic valve replacement, respectively through Hancock (27 mm) and Mitroflow (21 mm), was referred to our Centre for dyspnoea on mild efforts. Echocardiography revealed severe degeneration of both prosthetic valves, with moderate mitral stenosis (mean pressure gradient – MG – 6 mmHg) and severe central regurgitation, and high transaortic pressure gradients (MG 58; peak pressure gradient – PG – 103 mmHg). Pulmonary hypertension, mild right ventricle dysfunction and reverse flow in hepatic veins were evident. Results The first intervention was Valve–in–Valve Transcatheter Aortic Valve Implantation (ViV TAVI) with CoreValve Evolut PRO+ (23 mm), followed however by recoil determining moderate aortic stenosis (MG 25, PG 47 mmHg). Hence, as both the left prosthetic valves needed treatment, we decided to plan an elective percutaneous procedure aimed to treat both of them. Aortic ViV cracking was successfully obtained through non–compliant Atlas Gold Balloon (22 mm). Then, transseptal puncture by Brockenbrough needle and SL0 dilator sheath system was used to gain access to the left atrium. Finally, after interatrial shunt pre–dilation, Edwards Sapien 3 Ultra (26 mm) was applied as Mitral ViV during rapid ventricle pacing. Echocardiography showed relevant decrease of aortic pressure gradients (MG 11, PG 19) and downgrading of mitral regurgitation from severe to mild, despite unvaried persistent moderate mitral stenosis and signs of chronic severe pulmonary hypertension. The patient was dismissed in 3 days, after adjusting medical therapy. Conclusions Dysfunction of prosthetic heart valves is challenging to be approached, particularly when involving more than one. The expertise of the Centre assumes great importance in this delicate clinical setting. More explanations are further needed to define type and timing of percutaneous intervention aimed to the treatment of multiple prosthetic valves.

The aim of this work was to develop an efficient method for the selective extraction and analysis of fenoxycarb, a carbamate pesticide, in mussel samples using a molecularly imprinted solid-phase extraction device. The optimization of molecularly imprinted polymer synthesis was performed using the experimental design under the response surface methodology approach. A fast rebinding study and Freundlich isotherm adsorption were carried out to calculate binding capacity B, site number n, and affinity constant Kf . The optimum molecularly imprinted polymer was successfully used as sorbent of a solid-phase extraction cartridge for the determination of fenoxycarb in real mussel samples. The range of linearity was 0.3-30 mg/L with a correlation coefficient of 0.991. The limit of detection was 0.247 mg/kg. The recovery of fenoxycarb extracted from mussel samples of Mediterranean sea was 97% (n = 3) with relative standard deviation between 6 and 7% proving the reliability of the developed method.

The volume of contrast to creatinine clearance ratio (CV/CrCl) is a useful indicator of the risk of acute kidney injury (AKI) in patients undergoing percutaneous interventional procedures. Association between CV/CrCl and adverse outcome after transcatheter aortic valve implantation (TAVI) was suggested but it is not well established. A large retrospective multicenter cohort of 1381 patients treated with TAVI was analyzed to assess the association between CV/CrCl and the risk of AKI and mortality at 90 days and 1 year after TAVI. Patients receiving renal replacement therapy at the time of TAVI were excluded. CV/CrCl ≥ 2.2 was associated with the risk of AKI and 90 days mortality after TAVI after adjustment for age, sex, diabetes, baseline left ventricular function, baseline chronic kidney disease (CKD), previous myocardial infarction and peripheral vascular disease (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.09-1.22, p 0.0001). Importantly, CV/CrCl was associated with the adverse outcome independently from the presence of baseline CKD (p for interaction = 0.22). CV/CrCl was independently associated with the individual components of the composite primary outcome including AKI (odds ratio: 1.18, 95% CI: 1.08-1.28, p 0.0001) and 90 days mortality (HR: 1.90, 95% CI: 1.01-3.60, p = 0.047) after TAVI. AKI (HR: 1.94, 95% CI: 1.21-3.11, p = 0.006) but not CV/CrCl was associated with the risk of 1-year mortality after TAVI. CV/CrCl is associated with excess renal damage and early mortality after TAVI. Procedural strategies to minimize the CV/CrCl during TAVI may improve early clinical outcomes in patients undergoing TAVI.

Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1–2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (

Aims Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree in ∼20% of intermediate coronary lesions. The physiological pattern of disease has a significant influence on FFR-iFR discordance. However, if the pattern of disease (diffuse vs. focal) impacts on QFR accuracy and on its agreement with FFR and iFR remains unknown. Methods and results 194 unselected patients with 224 intermediate coronary lesions were investigated with iFR, FFR and QFR. The physiological pattern of disease was independently assessed with iFR Scout pullback in all the cases by two expert interventional cardiologists who were blinded to the clinical presentation, patient characteristics, coronary angiography and QFR results. A predominantly physiologically focal pattern was observed in 81 (36.2%) lesions, whereas a predominantly physiologically diffuse was observed in 143 (63.8%) cases. QFR demonstrated a significant correlation (r = 0.581, P Conclusions QFR has a good diagnostic accuracy in assessing myocardial ischemia independently of the pattern of coronary disease. However, the physiological pattern of disease has an influence on the QFR/IFR disagreement, which occurs in ∼20% of the cases. The QFR virtual pullback correctly defined the physiological pattern of disease in the majority of the cases using the iFR pullback as reference.

Aims PCI timing in patients undergoing TAVI is still controversial, with most cases treated before TAVI, because of concerns about potential ischaemic complications during valve replacement. This study aims to compare procedural and in-hospital outcomes in patients undergoing PCI before or after TAVI. Methods and results Patients undergoing TAVI and PCI from 2010 to 2021 at Verona University Hospital were included. High-risk PCI were defined when performed in unprotected left main, proximal left anterior descending, proximal dominant right coronary artery or in 3-vessel disease. The primary endpoint was the cumulative incidence of any TAVI procedural complication and in-hospital adverse events (VARC-3 criteria). 129/940 TAVI patients underwent PCI was performed before TAVI in 33.4% of cases. Most patients (76.4%) were at high-risk. The primary endpoint occurred in 30.2% PCI pre-TAVI vs. 23.3% post-TAVI (HR: 0.72; 95% CI: 0.26–2.86; P = 0.671); and in 37.9% vs. 18.5% respectively, among high-risk PCI (HR: 1.62; 95% CI: 0.86–3.76; P = 0.102). At 24 months, MACCE-free survival was comparable (PCI pre-TAVI 91.7% vs. post-TAVI 97.5%, HR: 0.88, 95% CI: 0.13–4.77, P = 0.765). Conclusions PCI performed after TAVI does not expose patients to higher risks of peri-procedural or long-term complications when compared with pre-TAVI procedures, even in presence of high-risk lesions. 377 FigureAn example of post-TAVI high risk PCI. Pre-TAVI coronary angiography showed ostial left main critical lesion (A). After Symetis Aortic valve deployment, balloon angioplasty and stent implantation were performed (B and C) with good final angiographic result (D).

Aims The volume of contrast to creatinine clearance ratio (CV/CrCl) is a useful indicator of the risk of acute kidney injury (AKI) in patients undergoing percutaneous interventional procedures. Association between CV/CrCl and adverse outcome after transcatheter aortic valve implantation (TAVI) was suggested but it is not well established. Methods and results A large retrospective multicentre cohort of 1381 patients treated with TAVI was analysed to assess the association between CV/CrCl and the risk of AKI and mortality at 90 days and one year after TAVI. Patients receiving renal replacement therapy at the time of TAVI were excluded. CV/CrCl was associated with the risk of AKI and 90 days mortality after TAVI after adjustment for age, sex, diabetes, baseline left ventricular function, baseline chronic kidney disease (CKD), previous myocardial infarction and peripheral vascular disease (HR: 1.16, 95% CI: 1.09–1.22, P Conclusions CV/CrCl is associated with excess renal damage and early mortality after TAVI. Procedural strategies to minimize the CV/CrCl during TAVI may improve early clinical outcomes in patients undergoing TAVI.

Computed tomography (CT) is a diagnostic medical imaging modality commonly used to detect disease and injury. Contrast agents containing iodine, such as iohexol, are frequently used in CT examinations to more clearly differentiate anatomic structures and to detect and characterize abnormalities, including tumors. However, these contrast agents do not have a specific tropism for cancer cells, so the ability to detect tumors is severely limited by the degree of vascularization of the tumor itself. Identifying delivery systems allowing enrichment of contrast agents at the tumor site would increase the sensitivity of detection of tumors and metastases, potentially in organs that are normally inaccessible to contrast agents, such as the CNS. Recent work from our laboratory has identified cancer patient-derived extracellular vesicles (PDEVs) as effective delivery vehicles for targeting diagnostic drugs to patients’ tumors. Based on this premise, we explored the possibility of introducing iohexol into PDEVs for targeted delivery to neoplastic tissue. Here, we provide preclinical proof-of-principle for the tumor-targeting ability of iohexol-loaded PDEVs, which resulted in an impressive accumulation of the contrast agent selectively into the neoplastic tissue, significantly improving the ability of the contrast agent to delineate tumor boundaries.

This proposal will analyse the motivations that led intellectuals of the third century B.C. to create the canon of Wonders of the World. It is emblematic that the ancient sources do not speak of the Wonders of one civilisation or another; they speak of the Wonders of the World, making this one of the first examples of interculturality in which the protagonist is Man side by side with his History. In the contemporary world, where reference is made to belong to a common reality gravitating around the Mediterranean, we look for a “global” culture made of images that can express an idea of universality. The wonders of the world could be the key to recomposing under the common denominator of a glorious past, a fragmented reality, such as the Mediterranean one.

Endotracheal intubation (EI) in domestic cats is an important skill that veterinary students learn in order to perform anesthesia safely in this species. Implementing a 3D-printed larynx model (LaryngoCUBE) during the instruction process may improve student’s learning of EI in felines. Twenty-two third-year students performed EI in cats with standard training (ST), and 16 students trained with the model (MT) the day before the laboratory. It was evaluated whether training with the model decreases the time and number of EI attempts, students’ perceived difficulty performing EI using a visual analog score (VAS; 0 cm = very easy, 10 cm = extremely difficult; median [minimum–maximum]), and the incidence of failure to perform EI. The EI time on ST (58 [18–160] seconds) was longer, but not statistically different from MT (29 [13–120] seconds; p = .101). The number of EI attempts on ST (2 [1–3]) was higher than MT (1 [1–3]; p = .005). The VAS on the ST and MT were 4.5 (0.0–10.0) cm and 3.0 (0.2–10.0) cm, respectively ( p = .029). The failure rate was 27% on the ST and 25% on the MT ( p = 1.000). Students who practiced with a larynx model took fewer attempts to perform EI, tended to be faster, and found that EI was easier. However, the EI success rate in MT was not improved.

Objectives This study aimed to predict the displacement of self-expanding transcatheter heart valves (THV) during final deployment. Background Accurate device positioning during transcatheter aortic valve implantation (TAVI) is crucial for optimal results. Methods At our institution, 103 patients who underwent transfemoral TAVI with Evolut R were retrospectively identified. Multiple linear regression models were created, and a predictor equation was built to quantify the factors that may affect THV behavior. Results Multiple linear regression analysis for THV displacement on the left coronary cusp (LCC) identified the angle between the THV and the ascending aorta (ATA), predilation, and less operator experience as independent predictors of upward displacement, whereas estimated glomerular filtration rate (eGFR) was inversely related with THV behavior (95% confidence interval: 0.219 to 0.340, 0.447 to 2.092, 0.165 to 1.757, and -0.053 to -0.011, respectively). Predictors of THV displacement on the noncoronary cusp side could not be identified using this model. Conclusions The ATA at the point of recapture, predilation, and less operator experience were independent predictors of upward displacement of THV on the LCC side. eGFR was an independent predictor of THV downward displacement on the LCC side. Of them, the ATA was the strongest predictor. Physicians may need to adjust this angle adequately before deployment to achieve the appropriate position.

Gold nanomaterials hold great potential for biomedical applications. While this field is evolving rapidly, little attention has been paid to precise nanoparticle design and functionalization. Here, we show that when using proteins as targeting moieties, it is fundamental to immobilize them directionally to preserve their biological activity. Using full-length leptin as a case study, we have developed two alternative conjugation strategies for protein immobilization based on either a site-selective or a nonselective derivatization approach. We show that only nanoparticles with leptin immobilized site-selectively fully retain the ability to interact with the cognate leptin receptor. These results demonstrate the importance of a specified molecular design when preparing nanoparticles labeled with proteins.

Effective and selective targeting of the αV β3 integrin subtype is of high relevance in cancer research for the development of therapeutic systems with improved efficacy and of diagnostic imaging probes. We report here a new class of highly selective, αV β3 -targeted gold nanoparticles (AuNPs), which carry cyclic 4-aminoproline-RGD semipeptides (cAmpRGD) as the targeting moiety immobilized at low surface density on the poly(ethylene glycol) (PEG)-based nanoparticle coating. We show that these nanoparticles are potent inhibitors of the integrin-mediated melanoma tumor cell adhesion to vitronectin and are selectively internalized via receptor-mediated endocytosis. Furthermore, we have developed bifunctional cAmpRGD-functionalized AuNPs by conjugation of a fluorophore (FAM or TAMRA) to a separate set of reactive groups on the PEG-based coating. These bifunctional AuNPs not only recapitulate the binding properties of cAmpRGD-AuNPs but also can be visualized via confocal laser microscopy, allowing direct observation of nanoparticle internalization. The peculiar molecular design of these nanoparticles and their precisely defined architecture at the molecular level accounts for their selective integrin binding with very low nonspecific background.

l-Kynurenine is an endogenous metabolite generated by the catabolic pathway of l-tryptophan and it could be a potential biomarker to test the efficacy of several checkpoint inhibitors that have already reached the clinical trials in the antitumor therapy. Thus, a molecularly imprinted polymer specific for the recognition of this metabolite was synthesized and used as innovative system in solid-phase extraction technique for the specific extraction and quantification of l-kynurenine in human urine. The off-line system was firstly tested on l-kynurenine standard solutions, allowing recoveries up to 97.7% (relative standard deviation = 2.2%) and then applied to fortified and deproteinated human urine samples, where a recovery of 84.1% (relative standard deviation = 3.1%) was obtained. The method was validated and it revealed a good linearity in the range of 0.157-20 μg/mL (r2 = 0.9992). The optimized procedure demonstrated a good feasibility on biological samples, allowing a ready quantification of l-kynurenine in the human urine, where the metabolite was found at a very low concentration (0.80 μg/mL). The extraction system developed could attract attention of pharmaceutical industries for l-kynurenine production as potential drug in the treatment of autoimmune disorders through its extraction and purification from biological matrixes.

Orientadores : Paulo Augusto Valente Ferreira Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica e de Computação Doutorado

BackgroundExcessive production of mitochondrial reactive oxygen species (ROS) is a central mechanism for the development of diabetes complications. Recently, hypoxia has been identified to play an additional pathogenic role in diabetes. In this study, we hypothesized that ROS overproduction was secondary to the impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia.MethodsThe dynamic of ROS levels was analysed in the blood of healthy subjects and individuals with type 1 diabetes after exposure to hypoxia (ClinicalTrials.gov registration no. NCT02629406). The relation between HIF-1, glucose levels, ROS production and its functional consequences were analyzed in renal mIMCD-3 cells and in kidneys of mouse models of diabetes.ResultsExposure to hypoxia increased circulating ROS in subjects with diabetes, but not in subjects without diabetes. High glucose concentrations repressed HIF-1 both in hypoxic cells and in kidneys of animals with diabetes, through a HIF prolyl-hydroxylase (PHD) - dependent mechanism. The impaired HIF-1 signaling contributed to excess production of mitochondrial ROS through increased mitochondrial respiration that was mediated by Pyruvate dehydrogenase kinase 1 (PDK1) and was followed by functional consequences. The restoration of HIF-1 function attenuated ROS overproduction despite persistent hyperglycemia, and conferred protection against apoptosis and renal injury in diabetes.ConclusionsWe conclude that the repression of HIF-1 plays a central role in mitochondrial ROS overproduction in diabetes and is a potential therapeutic target for diabetic complications. These findings are highly significant and timely since the first PHD inhibitor that can activate HIF-1 has been newly approved for clinical use.

The diagnostic workflow of patients with cognitive decline needs an extensive clinical evaluation. The use of FDG-PET can be helpful because the finding of a rather specific pattern of hypometabolism could point to specific neurodegenerative disorders. In patients with memory impairment and visuo-spatial deficits, FDG-PET may reveal a pattern of temporo-parietal hypometabolism that is associated with Alzheimer’s disease or a more extended area of hypometabolism that spreads to the occipital cortex, as in posterior cortical atrophy indicating signs of neurodegeneration in the associative visual cortex. In the spectrum of fronto-temporal lobe degeneration, FDG-PET is used to support the diagnosis by excluding AD and to identify areas of hypometabolism that are associated with the behavioural variant of FTD or with progressive primary aphasia. When cognitive impairment develops along with parkinsonism, FDG-PET can be used to differentiate among the different forms of disorders, such as dementia with Lewy bodies, progressive supranuclear palsy and cortico-basal degeneration, occurring with different specific pattern of altered metabolism. In this pictorial essay, we present a series of clinical cases in which the use of FDG-PET contributed to the final diagnosis.

Significant evidence is available in the literature justifying the search for treatment technologies or process combinations to improve the decomposition of dozens of pharmaceuticals in wastewater. Conventional processing techniques are insufficient in removal of the pharmaceuticals, for having resistant waste and low biodegradability. Electron beam irradiation (EBI) may play an important role in this context, and relatively low doses have been reported for such purposes. The objective of this study was to apply the process of irradiation with electron beam in order to reduce the toxic effects of fluoxetine, propranolol, and a binary mixture of these pharmaceuticals in aqueous solution. Ecotoxicological tests conducted in two model organisms, Daphnia similis microcrustacean, and Vibrio fischeri bacterium. It was observed that D. similis was more sensitive to the pharmaceuticals and binary mixture, when compared to V. fischeri. When EBI was applied, all doses showed significant reduction of toxicity for D. similis, and the opposite for V. fischeri, when only 5.0 kGy showed a significant reduced of toxicity for the pharmaceuticals and binary mixture. 5.0 kGy was the best removal efficiency for toxicity, approximately 80% for D. similis and 20% for V. fischeri.

Among the therapeutic options of drug-resistant focal epilepsies, surgical treatment is the most effective treatment, provided that the location of the epileptogenic area is identified. Among the imaging modalities, MRI represents the fundamental method for the identification of structural lesions. However, despite the continuous technical progress of the equipment, a significant proportion of patients do not present recognizable alterations with MRI. PET with 18F-FDG is a method of investigation of cerebral metabolism and can be useful to identify the epileptogenic area and the extension of the epileptogenic network. In this pictorial essay, the role of PET is briefly reported and some representative clinical cases presented. In epilepsies of the mesial temporal lobe, PET is useful for confirming the laterality of the epileptogenic area and for confirming the cases of bi-temporal epilepsy, in which surgery is contraindicated, as well as to recognize remote areas of altered metabolism that could change the planning of surgery. In extra-temporal focal epilepsies, 18F-FDG PET can detect focal metabolism alterations indicative of lesions such as focal cortical dysplasia, even when the MRI is negative. However, for the correct interpretation of 18F-FDG, MRI is necessary. With the use of PET/MRI hybrid devices, the best accuracy of PET is obtained, but the use of registration softwares is, however, suitable for the purpose of accurately identifying the cerebral cortex and avoiding errors in the interpretation of PET. The text describes the protocol for acquiring and recording MRI and 18F-FDG images for clinical use in use in our Department of Pre-surgical Diagnostics.

We have recently demonstrated that iterative reconstruction algorithms with resolution recovery require the adoption of specific normal databases (NDBs) for perfusion SPECT quantification. This work was aimed at investigating the impact of patient low-dose imaging on NDBs and percent summed rest (SR%) and stress (SS%) scores.Assuming that count statistics of shorter acquisition time may simulate that of lower patient dose, three simultaneous scans were acquired (BrightView, Philips) with different acquisition-time/projection: 30, 15 and 8 s (from 100% to 25% of the reference). Fifty-two normal patients with low likelihood of coronary artery disease were enrolled and three homemade NDBs were then generated and compared (Astonish™ algorithm with default parameters): 100%-HM-NDBs, 50%-HM-NDBs and 25%-HM-NDBs. SR% and SS% were subsequently calculated for another group of 38 patients (normal/abnormal = 5/33). SR% and SS% values of 100%-HM-NDBs were compared with those obtained with the NDBs available on the workstation. Moreover, the impact of the study count statistics on perfusion scores was evaluated using the count-specific NDBs.Significantly higher standard-deviation values were found for 25%-HM-NDBs compared to the other HM-NDBs (p 0.02). Significantly higher SS% were also found for the 100%-HM-NDBs compared to the workstation NDBs (95%CI: 0.15-2.11%). Moreover, a post-hoc test showed significantly lower SR% and SS% for 25%-count statistics compared to 100%-HM-NDBs (p 0.03).NDBs and perfusion scores depend significantly on study count-statistics. A 50% reduction in patient dose is ultimately the limit for Astonish™ (with the default parameters) in order to prevent a significant variation in myocardial perfusion quantification.

Objectives: The aim of this study was to describe the sedative and some physiological effects of tiletamine?zolazepam following buccal administration (BA) in cats. Methods: Seven healthy spayed European Shorthair cats (three males, four female) were studied twice in this randomized, blinded, crossover study. Each cat received two doses of tiletamine?zolazepam by BA: the low-dose (LD) consisted of 5 mg/kg of each drug, and the high dose (HD) consisted of 7.5 mg/kg of each. Baseline systolic blood pressure (SAP), heart rate (HR), respiratory rate (RR) and a sedation score were recorded prior to administration of each treatment. The same variables plus the percentage of hemoglobin saturated with oxygen as measured by pulse oximetry (SpO 2 ) were recorded at predefined intervals for the next 2 h. Results: All cats completed the study. No retching or vomiting were observed. Hypersalivation was observed in 0/7 and 3/7 for LD and HD, respectively (P = 0.2). There were significant changes in scores over time for posture, response to clippers and response to manual restraint for both groups, without differences between groups. RR, HR and SAP changed significantly over time. SAP and RR were significantly lower for HD than for LD. No values for hemoglobin saturation

Before you use Visual Studio Code as the editor of your choice, it is convenient for you to know how the workspace is organized and what commands and tools are available, in order to get the most out of the development environment.