Cytotoxicity effects and differentiation potential of ormocer-based and nanohybrid composite resins on human dental pulp stem cells.

OBJECTIVE: to compare conventional nanohybrid (Ceram.x Spectra) and ormocer-based (Admira fusion) dental composite resins effects on human dental pulp stem cells (hDPSCs) in terms of cytotoxicity, self-renewal, migration and osteogenic differentiation. METHODS: hDPSCs were cultured in presence of different dilutions (undiluted, form 1:2 to 1:100) of CeramX (CX) and Admira fusion (AD) eluates and viability assay in standard or osteogenic conditions were performed. Samples and eluates were prepared according to ISO 10993-12. In addition, apoptosis, self-renewal and migration activity evaluations were carried out. Osteogenic differentiation potential was tested by Alkaline Phosphatase Activity, alizarin red staining and gene expression of specific markers (ALP, RUNX2, OCN, OPN and COL1α1). Statistical analysis was performed by means of a One-way analysis of variance (One-way ANOVA) followed by a Tukey's test for multiple comparison; results were presented as mean ± standard error of mean (SEM). RESULTS: Admira Fusion demonstrated to be highly biocompatible and showed positive effects on hDPSCs proliferation and differentiation; on the contrary, conventional nanohybrid composite showed to be more cytotoxic and without any notable effect on stem cells differentiation. Moreover, the obtained results were further corroborated by a significant upregulation of osteogenic differentiation markers obtained in presence of ormocer-based composite resin eluate. Specifically, in AD 1:50 group expression levels of ALP, Runx2, Col1α1 were double than control (ALP, p = 0.045; Runx2, p = 0.003; Col1α1, p = 0.001) and CX 1:50 (ALP, p = 0.006; RUNX2, p = 0.029; Col1α1, p = 0.005). Moreover, in the same group, OPN and OCN resulted about 5 times more expressed as compared to control (OPN, p = 0.009; OCN, p = 0.0005) and CX 1:50 (OPN, p = 0.012; OCN, p = 0.0006). SIGNIFICANCE: The less cytotoxicity obtained by AD than conventional nanohybrid composite may be attributed to a reduced monomers release in the oral environment, supporting the hypothesis of limited adverse effect and enhanced healing potential, mainly when the material is positioned in close contact with pulp tissue.

A systematic review of influenza virus in water environments across human, poultry, and wild bird habitats.

Influenza, a highly contagious acute respiratory disease, remains a major global health concern. This study aimed to comprehensively assess the prevalence of influenza virus in different aquatic environments. Using 43 articles from four databases, we thoroughly examined water matrices from wastewater treatment plants (WTPs) and other human environments, as well as poultry habitats and areas frequented by migratory wild birds. In WTP influents (10 studies), positivity rates for influenza A ranged from 0.0 % to 97.6 %. For influenza B (8 studies), most studies reported no positivity, except for three studies reporting detection in 0.8 %, 5.6 %, and 46.9 % of samples. Within poultry habitats (13 studies), the prevalence of influenza A ranged from 4.3 % to 76.4 %, while in environments frequented by migratory wild birds (11 studies), it ranged from 0.4 % to 69.8 %. Geographically, the studies were distributed as follows: 39.5 % from the Americas, 18.6 % from Europe, 2.3 % from South-East Asia and 39.5 % from the Western Pacific. Several influenza A subtypes were found in water matrices, including avian influenza (H3N6, H3N8, H4N1, H4N2, H4N6, H4N8, H5N1, H5N8, H6N2, H6N6, H7N9, H0N8, and H11N9) and seasonal human influenza (H1N1 and H3N2). The existing literature indicates a crucial requirement for more extensive future research on this topic. Specifically, it emphasizes the need for method harmonization and delves into areas deserving of in-depth research, such as water matrices pertaining to pig farming and prevalence studies in low-income countries.

Detection and full genomic sequencing of rare hepatitis E virus genotype 4d in Italian wastewater, undetected by clinical surveillance.

Hepatitis E is a liver disease caused by the hepatitis E virus (HEV), primarily transmitted through contaminated water or food. There are four different HEV genotypes in humans, with genotypes 1 and 2 being the most widespread. Genotypes 3 and 4 are found in animals and can also infect humans. Genotype 4 is prevalent in Asia, mainly in China. In Italy, only one outbreak of HEV-4 has been documented, which occurred in 2011, involving five patients. In 2013, HEV G4 was also detected in a pig farm. Since then, no further evidence of HEV genotype 4 has been found in the country. This study describes the first detection of HEV genotype 4, subtype d, in wastewater in central Italy, despite a lack of any clinical case reported in the area. By using a multiplex PCR protocol and two sequencing strategies, Illumina and ONT, the virus's complete genome was sequenced and characterized as subtype 4d. These findings shed light on the potential of environmental surveillance for infectious agents to improve our understanding of epidemiology and support public health efforts.

Wastewater surveillance of SARS-CoV-2 variants in October-November 2022 in Italy: detection of XBB.1, BA.2.75 and rapid spread of the BQ.1 lineage.

This study adds insight regarding the occurrence and spread of SARS-CoV-2 Variants of Concern (VOCs) and Variants of Interest (VOIs) in Italy in October and November 2022, by testing urban wastewater collected throughout the country. A total of 332 wastewater samples were collected from 20 Italian Regions/Autonomous Provinces (APs) within the framework of national SARS-CoV-2 environmental surveillance. Of these, 164 were collected in the first week of October and 168 in the first week of November. A ∼1600 bp fragment of the spike protein was sequenced by Sanger (for individual samples) and long-read nanopore sequencing (for pooled Region/AP samples). In October, mutations characteristic of Omicron BA.4/BA.5 were detected in the vast majority (91 %) of the samples amplified by Sanger sequencing. A fraction of these sequences (9 %) also displayed the R346T mutation. Despite the low prevalence documented in clinical cases at the time of sampling, amino acid substitutions characteristic of sublineages BQ.1 or BQ.1.1 were detected in 5 % of sequenced samples from four Regions/APs. A significantly higher variability of sequences and variants was documented in November 2022, when the rate of sequences harbouring mutations of lineages BQ.1 and BQ1.1 increased to 43 %, and the number of Regions/APs positive for the new Omicron subvariant more than tripled (n = 13) compared to October. Moreover, an increase in the number of sequences with the mutation package BA.4/BA.5 + R346T (18 %), as well as the detection of variants never observed before in wastewater in Italy, such as BA.2.75 and XBB.1 (the latter in a Region where no clinical cases associated with this variant had ever been documented) was recorded. The results suggest that, as predicted by the ECDC, BQ.1/BQ.1.1 is rapidly becoming dominant in late 2022. Environmental surveillance proves to be a powerful tool for tracking the spread of SARS-CoV-2 variants/subvariants in the population.

Impact of anatomy type of prostatic artery on the number of catheters needed for prostatic artery embolization.

PURPOSE: The purpose of this study was to assess the relationship between the number of microcatheters required for prostatic artery embolization (PAE) and the anatomy of the prostatic artery (PA). MATERIALS AND METHODS: All consecutive patients who underwent PAE between May 2017 and December 2018 were included. The anatomical description of the PAs was assessed by both global cone beam computed tomography and selective angiography and data on the resources used, in terms of microcatheters, were prospectively collected. RESULTS: A total of 215 consecutive patients (mean age, 66±8.7 [SD] years; range: 45-93 years), with a mean International Prostate Symptom Score of 21±7.4 (SD) and a mean prostate volume on magnetic resonance imaging of 88±38 (SD) mL (range: 30-200mL) underwent PAE. A single PA was observed in 347 hemipelvises (347/411; 84.4%) and double PAs in 64 (64/411; 15.6%). Eighty percent (173/215 patients) of PAEs were performed using a single microcatheter. Type I PA anatomy required significantly more microcatheters (1.15±0.39 [SD]; range: 1-3), than type II (1.04±0.19 [SD]; range: 1-2), type III (1.09±0.34 [SD]; range: 1-3) and type IV (1.06±0.27 [SD]; range: 1-2) (P=0.01 for all). CONCLUSION: PAE is feasible with limited per-intervention changes in devices for all types of PA anatomy encountered. This could help in the design of appropriate reimbursement policies in various healthcare settings.

Contrast-Enhanced Ultrasonography for the Early Evaluation of Prostate Artery Embolization.

AIM: To prospectively evaluate the feasibility and reproducibility of the semiquantitative measurement of the unenhanced area of the prostate by trans-abdominal contrast-enhanced ultrasound (CEUS) performed immediately after prostate artery embolization (PAE) as a prognostic factor of success. METHODS: Thirty-nine patients with PAE were prospectively included. They all underwent pre- and post-PAE trans-abdominal prostate CEUS. Two readers independently evaluated the pre- and post-PAE unenhanced area using a semiquantitative method: unenhanced areas were measured on 3 different slices (basis, middle, and apex) and reported to the whole prostate area. The mean of the three measures was reported semiquantitatively in classes of ten percent and quartiles. We evaluated correlation with clinical success, at 3 months after PAE, defined as a > 25% reduction in the International Prostatic Symptoms Score and a Quality of life < 3. RESULTS: Twenty-three patients who had bilateral PAE were analyzed. Pre-PAE trans-abdominal prostate CEUS showed visible early and marked enhancement of the entire prostate in all patients. After PAE, all patients had a semiquantitatively measured unenhanced area > 25%. The semiquantitative measurement was found to be highly reproducible, with an interclass correlation > 0.8. No correlation was found between the area of unenhanced tissue and clinical success evaluated at 3 months. CONCLUSION: Trans-abdominal prostate CEUS performed early after PAE provides reproducible results and is a valuable tool to evaluate unenhanced areas of the prostate. LEVEL OF EVIDENCE: 3, local non random sample.

3D-printed face protective shield in interventional radiology: Evaluation of an immediate solution in the era of COVID-19 pandemic.

PURPOSE: The purpose of this study was to report the clinical evaluation of a 3D-printed protective face shield designed to protect interventional radiologists from droplet transmission of the SARS-Cov-2. MATERIALS AND METHODS: A protective face shield consisting in a standard transparent polymerizing vinyl chloride (PVC) sheet was built using commercially available 3D printers. The 3D-printed face shield was evaluated in 31 interventional procedures in terms of ability to perform the assigned intervention as usual, quality of visual comfort and tolerance using a Likert scale (from 1, as very good to 5, as extremely poor). RESULTS: The mean rating for ability to perform the assigned intervention as usual was 1.7±0.8 (SD) (range: 1-4). The mean visual tolerance rating was 1.6±0.7 (SD) (range: 1-4). The mean tolerability rating was 1.4±0.7 (SD) (range: 1-3). CONCLUSION: The 3D-printed protective face shield is well accepted in various interventions. It may become an additional option for protection of interventional radiologists.

Mid-Term Results of Superior Rectal Artery and Coils for Hemorrhoidal Embolization with Particles Bleeding.

OBJECTIVES: To compare safety and clinical outcomes of embolization of the superior rectal arteries in patients with hemorrhoidal bleeding using particles and coils versus coils only. METHODS: We retrospectively reviewed data for patients undergoing embolization for chronic hemorrhoidal bleeding from January 2014 to April 2017. Embolization was performed with coils alone or with particles and coils. Clinical scores (Paris bleeding severity score, Goligher classification and quality of life score) were obtained, and embolization was performed with microparticles (300-500 µm) followed by fibered pushable coils. Clinical success was defined as an improvement of > 2 points in the Paris bleeding severity score, without complications. Outcomes were compared between the two groups in a matched-pairs analysis (1:1 scenario), with patients embolized with particles and coils as the study group and patients embolized with coils alone as the control. RESULTS: We treated 45 consecutive patients. After matched-pairs analysis, the final study population was 38 patients (19 study group and 19 controls). Clinical success did not differ significantly between the two populations: 63% for control group and 68% for the study group (p = 0.790). The median change in clinical score was - 3 [- 6; - 1] for the control group and - 3 [- 4; - 1] for the study group (p = 0.187). Grade 1 complications were reported in 15% of patients, with no major complications. CONCLUSIONS: Embolization was feasible, with a technical success of 100% and no major complications. Clinical success was obtained in 66% in patients with no difference when using combined embolization with particles and coils versus coils only.

An Approach to Prevent Frailty in Community Dwelling Older Adults: a pilot study performed in Campania region in the framework of the PERSSILAA project.

We developed and tested an innovative physical training method in older adults that embeds the gym program into everyday life in the most conservative way possible. Physical training was included in the activities of local parishes where older women from Southern Italy spend most of their free time and was delivered by trained physical therapists with the support of an ICT tool known as CoCo. 113 older women (aged 72.0 [69.0-75.0] years) noncompliant to conventional exercise programs participated to the study. 57 of them underwent the final anthropometric assessment and 50 the final physical tests. In study completers handgrip strength and physical performance evaluated with the chair-stand, the two minutes step and the chair-sit and -reach tests significantly improved. Quality of life as evaluated with the EuroQol-5dimension (EQ-5D) questionnaire improved as well. In conclusion, a training program designed to minimally impact on life habits of older people is effective in improving fitness in patients noncompliant to other to physical exercise programs.

Innovative Approaches to Active and Healthy Ageing: Campania Experience to Improve the Adoption of Innovative Good Practices.

The demographic projections on the European population predict that people aged over 60 will increase by about two million/year in the next decades. Since 2012, the Campania Reference Site of the European Innovation Partnership on Active and Healthy Ageing supports the innovation of the Regional Health System, to face up demographic changes and sustainability. Campania Reference Site provides the opportunity to connect loco-regional stakeholders in social and health care services (universities, healthcare providers, social services, local communities and municipalities), with international organizations, in order to adopt and scale up innovative solutions and approaches. This paper describes the building process of Campania Reference Site and the main results achieved, that have been allowing it to become a hub for open innovation in the field of active and healthy aging at regional, national and international level.

Correction to: Percutaneous Deep Venous Arterialization for Severe Critical Limb Ischemia in Patients With No Option of Revascularization: Early Experience From Two European Centers.

The fifth author's name was incorrectly published as "M. Messas". The correct name is "E. Messas". The original article has been corrected.

Percutaneous Deep Venous Arterialization for Severe Critical Limb Ischemia in Patients With No Option of Revascularization: Early Experience From Two European Centers.

PURPOSE: To report our initial experience of fully percutaneous deep venous arterialization (pDVA) for the treatment of chronic critical limb ischemia (cCLI) after failed distal angioplasty. MATERIALS AND METHODS: pDVA was performed in five consecutive patients by creating an arteriovenous fistula (AVF) between a below the knee artery and its satellite deep vein. In this early experience, only patients with failed prior interventional attempts at establishing flow with no distal targets for an arterial bypass were selected. Early technical success was defined as successful AVF creation and retrograde venous perfusion of the wound site. Patient demographics, procedural details, morbidity/mortality and wound healing outcomes were assessed prospectively. Patients were followed up in wound care centers, and graft patency was documented on duplex ultrasound. RESULTS: All five consecutive patients (mean age 58 years) underwent successful pDVA without any procedural complications. There were neither 30-day major adverse limb events nor major cardiovascular complications. Three out of the five patients (60%) had clinical improvement as observed by resolution of rest pain and complete wound healing. At the 1-month FU, one patient died and one patient received a major amputation. The median wound healing time was 39 weeks. CONCLUSION: pDVA is a safe and feasible vascularization alternative in patients with end-stage/no-option CLI. The early experience highlights the need for a multidisciplinary approach including a dedicated wound care service.

Comparison of Two Endovascular Steerable Robotic Catheters for Percutaneous Robot-Assisted Fibroid Embolization.

PURPOSE: To compare outcomes of percutaneous robot-assisted uterine fibroid embolization (UFE) using two different endovascular robotic catheters. METHODS: Twenty-one patients with a symptomatic uterine fibroid were prospectively enrolled in a single-center study to be treated with a percutaneous robot-assisted embolization using the Magellan system. Fourteen patients were treated using a first generation steerable robotic catheter, version 1.0 (group 1), and seven were treated using the new version 1.1 (group 2). Demographic, pathologic, and procedural variables were recorded. Dose Area Product (DAP) and physician equivalent doses were registered for each procedure. Procedural related complications and clinical midterm outcomes were also evaluated. RESULTS: Successful robot-assisted UFE was obtained in eight patients (57.1%) in group 1 and 7 patients (100%) in group 2 (p = 0.01). A successful robot-assisted catheterization of the internal iliac artery anterior branch was performed in all patients of both groups. Median selective target vessel catheterization time was 21.0 ± 12.8 vs 13.4 ± 7 min (p = 0.04) and total fluoroscopy time was 30.3 ± 11.2 vs 19.3 ± 5.9 min, respectively, in group 1 and 2. Mean DAP decreased from 18472.6 ± 15622 to 5469.1 ± 4461.0 cGy·cm2 (p = 0.04). All patients obtained a symptoms relief at 6 months follow-up. CONCLUSIONS: Robot-assisted uterine fibroid embolization is safe and effective. New version of steerable robotic catheter allows performing a faster procedure without related adverse events compared to old version.

[Recanalization procedure of the common femoral vein following iatrogenic femoral chronic occlusion: 3 cases]. / Recanalisation veineuse des membres inférieurs sur occlusion fémorale chronique iatrogène : à propos de 3 cas.

Common femoral vein occlusion (CFVO) is frequently found in patients with chronic venous insufficiency. The iatrogenic form, secondary to either central catheter or surgery, is very rare but highly symptomatic. Classical compression therapy barely improves the clinical status of these patients, making them suitable candidates for an interventional procedure for venous recanalization. METHODS: We report here three consecutive cases of iatrogenic CFVO referred to our outpatient clinic because the disease had an impact on daily life activities. We detail the recanalization procedure, the Doppler control and the short-term outcome. RESULTS: In each case, endovascular recanalization required rigid material (rigid guide or Colapinto needle) to cross the fibrous adhesions before angioplasty could be performed with stenting. The procedure required two attempts in each case, underlining its complexity, but eventually enabled effective recanalization. No major complication occurred per- or post-procedure. One month later, a duplex Doppler control confirmed the permeability of the common femoral vein. The patients had experienced rapid and significant symptom improvement. CONCLUSION: Patients suffering from severe chronic venous insufficiency caused by iatrogenic CFVO can benefit from endovascular recanalization. Although these procedures may be complex due to the extensive fibrosis at the Scarpa and require specialized equipment, no major complications were observed. Patency of the recanalization persisted at least one month after the procedure. Symptom relief was good.

Opposite effects of ß2-adrenoceptor gene deletion on insulin signaling in liver and skeletal muscle.

BACKGROUND AND AIM: ß2-Adrenoceptors (ß2-ARs) are G protein-coupled receptors (GPCRs) expressed in the major insulin target tissues. The interplay between ß2-AR and insulin pathways is involved in the maintenance of glucose homeostasis. The aim of this study was to explore the consequences of ß2-ARs deletion on insulin sensitivity and insulin signaling cascade in metabolically active tissues. METHODS AND RESULTS: We evaluated glucose homeostasis in skeletal muscle and liver of ß2-AR-null mice (ß2-AR-/-) by performing in vivo (glucose tolerance test and insulin tolerance test) and ex vivo (glucose uptake and glycogen determination) experiments. ß2-AR gene deletion is associated with hepatic insulin resistance and preserved skeletal muscle insulin sensitivity. Importantly, we demonstrate that hepatic ß2-AR regulates insulin-induced AKT activation via Grb2-mediated SRC recruitment through a Gi-independent mechanism. CONCLUSIONS: ß-AR stimulation contributes to the development of early stages of insulin resistance progression in the liver. Our findings indicate that the cross-talk between ß2-AR and insulin signaling represents a fundamental target towards the development of novel therapeutic approaches to treat type 2 diabetes and metabolic syndrome.

Embolization of the superior rectal arteries for chronic bleeding due to haemorrhoidal disease.

AIM: The aim of this study was to assess the safety and efficacy of the emborrhoid technique (embolization of the superior haemorrhoidal arteries) in patients ineligible for surgery. METHODS: Between January 2014 and April 2015, 30 consecutive patients (average age 58 years) suffering from disabling chronic bleeding due to haemorrhoidal disease and with a contraindication for surgery (n = 23) or with a failure of instrumental or surgical treatment (n = 7) underwent embolization. All cases were discussed at multidisciplinary meetings including a proctology specialist or a surgeon and an interventional radiologist. We performed super selective micro coil embolization (pushable 2-3 mm fibre coils) of the distal branches of the superior rectal arteries with a microcatheter, via a right femoral approach, under local anaesthesia. We assessed clinical outcome by evaluating bleeding and specific clinical scores relating to bleeding and changes in quality of life. RESULTS: Immediate technical success, with no complication, was achieved in 93% of cases. A mean of 3.1 arteries per patient was embolized, with a mean of 7.6 coils per patient. Median follow-up was 5 months. Clinical score improvement was observed in 72%, in 17 patients after a single embolization session, and in four additional patients after a second embolization session. No improvement in bleeding was observed in eight patients (28%). CONCLUSION: Distal coil embolization of the superior rectal arteries for disabling chronic bleeding due to haemorrhoidal disease is safe and effective in patients untreatable by surgery.

[Therapeutic endovascular procedures in aortitis]. / Place du traitement endovasculaire dans les aortites inflammatoires.

Aortitis is an inflammation of the aortic wall with an infectious or non-infectious origin, which often progresses to vascular complications. The open surgical approach is a high-risk procedure for these pathologies. Endovascular interventions have improved the prognosis of patients with aortitis complications. This manuscript describes the pathophysiology responsible for vascular complications and the role of endovascular approach for their treatment.

[Distal revascularization in diabetic patients with chronic limb ischemia]. / La revascularisation distale des diabétiques en ischémie critique.

Diabetes mellitus is an independent risk factor for peripheral artery disease. Life expectancy is 41 months for diabetic patients with an ischemic ulcer. The characteristics of diabetic arteriopathy make its treatment more difficult than in non-diabetic patients. Few data are available about the surgical treatment of arteriopathy in diabetic patients (including angioplasty or bypass), especially in case of distal arteriopathy. The choice of the procedure depends on multiple factors such as the disease localization, its extent, distal blood flow and vascular disease-related surgical risk. The principal aim of revascularisation is to restore direct flow to the foot in order to ensure wound healing and limb salvage. With percutaneous endoluminal angioplasty, limb salvage can be achieved in more than 80% of patients at 1-3 years. The percutaneous procedure is less invasive than open surgery, there are fewer complications, and morbidity and mortality rates are reduced; moreover, a second procedure remains possible in the future. With bypass surgery, the rate of limb salvage exceeds 80% at five years. Nevertheless, peri-operative mortality reaches 3% and arterial anatomy, patient-related risks factors or venous graft availability may be limitations. New endovascular techniques especially designed for the distal arteries of the lower limbs enable very distal revascularization with morbidity and mortality rates lower than with surgery.

New small molecules, ISA27 and SM13, inhibit tumour growth inducing mitochondrial effects of p53.

BACKGROUND: p53 is a transcription factor with tumour suppressor properties, which is able to induce mitochondrial apoptosis independently of its transcriptional activity. We recently synthesised two new compounds (ISA27 and SM13), which block p53-MDM2 interaction and induce apoptosis in p53 wild-type (WT) tumour cells. The aim of this study was to verify the effectiveness of these compounds in tumours carrying a mutated form of p53 gene with no transcriptional activity. METHODS: In vitro we evaluated the effectiveness of our compounds in cancer cell lines carrying WT, mutated and null p53 gene. In vivo study was performed in Balb/c nude mice and the mitochondrial-dependent apoptotic signalling was evaluated by western blot. RESULTS: Both ISA27 and SM13 reduced cell proliferation and induced apoptosis in vitro in cells carrying either p53 WT or mutated gene, suggesting that its effect is independent from p53 transcriptional activity. On the contrary, SM13 had no effect in a p53 null cell line. In vivo, ISA27 and SM13 induced cancer cell death in a dose-dependent manner through the activation of the mitochondrial-dependent death signalling in p53-mutated cells. In vivo, SM13 reduced tumour growth. CONCLUSIONS: Our study proposes SM13 as anticancer compound to use for the treatment of p53-dependent tumours, even in the absence of p53 transcriptional activity.