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Funding Acknowledgements Type of funding sources: None. Background The Global Registry of Acute Coronary Events (GRACE) risk score is widely recommended for risk assessment in patients with acute coronary syndrome (ACS). The Charlson Comorbidity Index (CCI) is a recognized measure of comorbid burden, and a useful tool for estimating prognosis in patients with multiple coexisting illnesses. Despite it has been validated in the context of ACS-related mortality, scarce and conflicting data still exist about the role of the CCI when added to the traditional GRACE risk score for outcome prediction in patients with acute coronary syndrome (ACS). Purpose The assessment of the potential predictive value of the CCI both for short, and long term all-cause mortality, in a contemporary ACS population, and its potential adding value beyond the GRACE risk score. Methods All consecutive admission due to ST-elevation myocardial infarction-STEMI, non ST elevated myocardial infarction-NSTEMI, and unstable angina-UA, from 01/01/2018 to 31/12/2020 were retrospectively reviewed from an internal database of a tertiary cardiac center in Italy. Logistic and Cox proportional regression analysis were performed in order to assess the contribution of the CCI on short and long term mortality. In order to specify the CCI adding value to the GRACE score, several measures of improvement in discrimination (increase in the area under the receiver-operating characteristic curve-AUC, the integrated discrimination improvement-IDI, and the continuous net reclassification improvement-cNRI>0) , were implemented. Robustness of the results were assessed through an internal validation procedure with bootstrapping. Results A total of 1310 patients (646 STEMI, 588 NSTEMI, and 76 UA) were identified. Almost 28% were female, and the median age was 68 (58-78). 97 (7,4%) and 136 (11,2%) deaths occurred, respectively, in hospital and during long term follow-up (median follow-up time: 12 months; IQR: 8-23). After multivariate logistic regression analysis the CCI was not associated with in-hospital death, while it was significantly and independently associated with the long-term mortality along with GRACE score (HR: 1,33, 95% CI: 1,22-1,43; p0: 0.678, p < 0.001, Table 1) and integrated discrimination improvement (IDI: 0.08, p < 0.001). Conclusion The CCI is a predictor of long-term mortality and improves risk stratification of patients with ACS over the GRACE risk score.

Aim The present narrative review aimed to shed light on the use of laser systems for gingival retraction procedures necessary for the exposure of iuxta- and sub-gingival finish lines before impression making in fixed prosthodontics. Methods An extensive search of the literature was made on the electronic databases of Pubmed (Medline), Scopus, Embase, Google Scholar, Dynamed, and Open Grey. No limitations were applied to the date of publication. The following keywords and MeSH terms were used: “gingiva”, “displacement”, “troughing”, “retraction”, and “laser”. Results Out of 344 studies found, 25 records were included for review. Laser systems are efficient in gingival retraction, allowing better intraoperative haemostasis control and postoperative patient comfort than other surgical troughing procedures. Laser- mediated gingival displacement seems to be safe particularly in the case of thick gingival biotype. Conclusions As regards laser-related issues in prosthodontics such as pre-setting protocols of laser devices, the best laser system in gingival retraction, their use around implants and effectiveness compared to other troughing systems, further in vitro, in vivo, and randomized controlled trial studies are needed.

Background Although interest in frailty has expanded among cardiology experts over the past 2 decades, its integration, as part of cardiovascular disease management, is still lacking, above all in the acute cardiac care setting. The Clinical Frailty Scale (CFS) is a brief guided tool to assess frailty in hospital settings without specialist equipment. Purpose Our objective was to test the performance of the CFS in an older, unselected population, admitted to an Intensive Cardiac Care Unit (ICCU) during the year 2019. Methods The study sample included 431 patients ≥65 years old, admitted to an ICCU of a tertiary cardiac center in Italy. The CFS ranged from “very fit: 1” to “terminally ill: 9”, but it was considered present at a score ≥5. Our primary endpoint was defined by a combination of severe complications requiring critical care and in-hospital death. The data were collected from the hospital discharge summary and the electronic chart records. Results 158 patients (36.7%) were frail. These individuals had greater comorbidity and higher in-hospital mortality (Table 1). After a multivariable logistic regression analysis, 4 predictors were identified: signs of congestive heart failure (OR: 8.51, 95% Confidence Interval-CI: 4.63–14.6; p Conclusions The CFS is a simple guided frailty tool that may enhance outcome prediction in the acute cardiac care setting. These findings merit evaluation in larger cohorts of unselected patients. Funding Acknowledgement Type of funding sources: None.

Background Amelogenesis Imperfecta (AI) is a syndromic entity comprising several clinical conditions, mostly genetic- based, affecting quality and quantity of enamel. The use of digital tools can be advantageous to enhance communication between the dental team and patients. Moreover, a full digital approach would allow to check each single clinical step according to the treatment plan with a backward approach. The aim of this case report is to describe a multidisciplinary treatment program of a young patient with severe open bite and amelogenesis imperfecta, whose restorative rehabilitation was planned in a full-digital workflow, from the initial communication phase up to the final prosthodontic rehabilitation. Case report An 8-year old female patient was diagnosed with a Class II division 1 malocclusion, severe open bite and AI. The treatment plan included 3 phases: the elimination of the tongue interposition habit and the anterior open bite, the orthodontic correction of dental deviation and leveling of both dental arches and a prosthetic rehabilitation. The extraction of the four first molars corrected the canine and molar Angle Class II relationships, deviation of the midline and repositioning of the maxillary incisors on the sagittal plane. Feldspathic ceramics was used in anterior sites to enhance the esthetic outcome. CAD/CAM hybrid ceramo-polymeric restorative material (PICN) was chosen for posterior regions. Conclusion The outcomes of the present case report proved that the planned objectives were satisfactorily obtained thanks to proper treatment planning, full digital workflow and the patient’s optimal compliance with the extraoral device.

Aim The present paper aimed to assess the accuracy gradient of scans made using an intraoral scanner (IOS) on a totally edentulous maxilla and the effectiveness of artificial markers. Materials and methods A reference scan was made by scanning a fully edentulous upper jaw cast (RC) with a dedicated metrological machine. On the RC, an IOS was used to make 10 scans then superimposed to detect their area accuracy gradient. Artificial markers with a diameter of 2 mm were placed in the less accurate areas following two approaches. In the first one, semispherical resin composite markers were used. In the second approach, a dermographic pen was used to draw circular flat markers. Three experimental groups (n = 10) were obtained: “no markers” for the control group without markers, “embossed markers” for resin composite markers, and “flat markers” for ink-drawn ones. The scans were processed into a specialized software, where trueness and precision were measured in millimeters. Descriptive statistics (95% C.I.) were conducted, also, the Games-Howell and Kruskal-Wallis tests (α = .05) were used to investigate differences between groups. Results Mean values for trueness were: no markers 48.8 (39.2- 58.3); embossed markers 39.2 (37.5-40.8); flat markers 60.5 (47.7-73.4), with statistically significant differences between embossed and flat markers (p = .011). Mean values for precision were: no markers 46.7 (29.7-63.7); embossed markers 41.4 (34.7- 48); flat markers 99.8 (69.3-130.3), with significant differences between embossed markers and flat ones (p = .008) and between the latter and the control group (p = .005). Minor accuracy was detected at both tuberosities, palate, posterior aspect of the papilla, and flattened areas of the ridges. Conclusions To improve IOS scans accuracy on the totally edentulous upper jaw, it is suggested to place embossed markers, rather than flat ones, in the areas of minor accuracy.

Background Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs). Objectives This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD. Methods This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy. Results Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life. Conclusions In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253)

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin-proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells.

This paper provides the design formulas for achieving a coupling-independent regime for a wireless power link consisting of magnetically coupled parallel resonators. It is demonstrated that for a strongly coupled link a performance independent of the coupling coefficient can be realized by an appropriate selection of the operating frequency.

Background Strenuous and chronic exercise training can have detrimental effects on cardiac morphology and function. Our aim was to evaluate the cardiac adaptation between 2 different specialties' endurance athletes: marathon runners (M) and ultra-trailers (UT). Methods 47 M (age 45±7, men 32; training: 18 (9-53) years*days/week), 41 UT (age 42±9, men 38, training: 30 (15-66) years*days/week) were submitted in rest condition to conventional 2D echocardiography and Speckle-Tracking echo (STE) (Beyond Diogenes 2.0, AMID) during agonistic season and compared with 15 age matched sedentary individuals (S) (age 43±6, men 10). Results Left ventricle (LV) global longitudinal strain (GLS) and global radial strain (GRS) were increased in M and UT compared to S (see table) without differences in LV anatomy and function. Right ventricle (RV) end-diastolic area (p=0.026), fractional area changing (p=0.008) and RV GLS were increased in UT compared to M. Moreover UT showed larger right atrium (RA) volume compared to M (p=0.03) and S (p=0.003). RA GLS was reduced in UT compared to M while the RA Global Circumferential Strain was significantly increased in UT. After adjusted for age, sex and HR as covariates, UT showed a reduced RA GLS (OR 0.907; CI 0.856-0.961) and increased RV FAC (OR 1.172; CI: 1.044-1.317) compared to M; while when compared to S subjects, UT showed increased RA volume (OR 1.048; CI 1.002-1.096) and RV GLS (OR 0.667; CI 0.490-0.907). Conclusion UT showed higher RV and RA morphological and functional remodeling in comparison with M. 2D-STE is a useful tool to investigate the deformation dynamic in different sport specialties. Further studies will be necessary to clarify the long-term consequences for cardiac health due to myocardial perturbations. MUTSpLV GLS-28.59±3.43*-27.64±4.18*-24.82±4.53

Background The fundoscopic examination of hypertensive patients, which is an established hypertension-related target organ damage (TOD), tends to be underutilized in clinical practice. We sought to investigate the relationship between retinal alterations and left atrium (LA) volumes by means of real-time, three-dimensional echocardiography (RT3DE), which is the most pivotal predictor of diastolic dysfunction. Methods Our population consisted of 88 consecutive essential hypertensive patients (age 59.2 ± 1.2 years, 53 females) without overt cardiovascular disease. All subjects underwent a fundoscopy examination and were distributed into five groups according to the Keith-Wagener-Barker (KWB) classification. Comprehensive transthoracic echocardiographic and RT3DE measurements were performed to assess LA volumes and phasic functions. Results The four groups (KWB grades 0-4: including 26, 20, 26, and 16 patients, respectively) did not differ with regards to age, gender, or metabolic profile. There were no significant differences between groups with regards to parameters reflecting left ventricle (LV) systolic function and diastolic dysfunctions in conventional echocardiography, except isovolemic relaxation time (IVRT) and deceleration time (DT). Nevertheless, patients in the higher KWB category had higher values of LA volumes (LA maximal volume, LA minimal volume, preatrial contraction volume, LA total stroke volume, LA active stroke volume, p< 0.001) regarding RT3DE (table 1). There is also a significant relationship between preatrial contraction volume and duration of HT (r: 0.67, p

Aim: The use of all-ceramic conservative occlusal veneers is becoming more popular in the clinical setting thanks to the recent improvement of the mechanical and esthetical properties of the restorative materials. Furthermore, the option of CAD/CAM fabrication may constitute a further advantage for both clinicians and patients. Since little is known about the influence of the occlusal veneer preparation design on the marginal fit of the final restoration, the present study compared the marginal fit of two preparation designs. Methods: Sixteen maxillary molars were selected from a pool of freshly extracted teeth and received 1-mm cusp reduction by using silicon indexes as reference. The teeth were randomly divided into two groups identified by the preparation design: conservative full-coverage occlusal veneer with a 90° rounded shoulder margin (n=8) and marginal chamfer (n=8). At the end of the preparation process, the exposed dentine surfaces were immediately sealed with a self etch adhesive system. Lithium disilicate restorations (IPS e.max CAD) were produced with the Cerec 3 CAD/CAM system. The intaglio surface of the occlusal veneers was conditioned with hydrofluoric acid and silane, while the tooth surface underwent silicatization, enamel etching, and adhesive system application. The occlusal veneers were luted with Variolink II cement. The specimens were embedded into acrylic resin simulating the periodontal ligament with a layer of vinyl polysiloxane; then, they were chewing machine (1,250,000 cycles, 1 Hz, 5-55°C). A quantitative marginal fit evaluation was performed observing at the scanning electron microscope resin replicas of the specimens obtained before and after the thermomechanical aging simulation. For each replica, a single trained blinded operator measured the marginal gap along 120 equidistant points of the adhesive interface. Collected data were tested for the assumptions for using parametric tests. The marginal fit measured at different experimental time points was compared within the same group with a paired sample t-test, while the two groups were compared at the same time point with an independent-sample t-test (p

This paper investigates the possibility of achieving a load– independent output voltage for a resonant inductive Wireless Power Transfer (WPT) link.

Contains fulltext : 177598.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. DESIGN: Observational cohort study. SETTING: Seven hundred and thirty ICUs in 84 countries. PATIENTS: All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. MEASUREMENTS AND MAIN RESULTS: ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock. CONCLUSIONS: In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death.

Hydrogen sulfide (H2S) is produced by the action of cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) or 3-mercaptopyruvate sulfurtransferase (3-MST). 3-MST converts 3-mercaptopyruvate (MPT) to H2S and pyruvate. H2S is recognized as an endogenous gaseous mediator with multiple regulatory roles in mammalian cells and organisms. In the present study we demonstrate that MPT, the endogenous substrate of 3-MST, acts also as endogenous H2S donor. Colorimetric, amperometric and fluorescence based assays demonstrated that MPT releases H2S in vitro in an enzyme-independent manner. A functional study was performed on aortic rings harvested from C57BL/6 (WT) or 3-MST-knockout (3-MST−/−) mice with and without endothelium. MPT relaxed mouse aortic rings in endothelium-independent manner and at the same extent in both WT and 3-MST−/− mice. N5-(1-Iminoethyl)-L-ornithine dihydrochloride (L-NIO, an inhibitor of endothelial nitric oxide synthase) as well as 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) did not affect MPT relaxant action. Conversely, hemoglobin (as H2S scavenger), as well as glybenclamide (an ATP-dependent potassium channel blocker) markedly reduced MPT-induced relaxation. The functional data clearly confirmed a non enzymatic vascular effect of MPT. In conclusion, MPT acts also as an endogenous H2S donor and not only as 3-MST substrate. MPT could, thus, be further investigated as a means to increase H2S in conditions where H2S bioavailability is reduced such as hypertension, coronary artery disease, diabetes or urogenital tract disease. © 2018 Elsevier Inc.

The aim of this study is to evaluate the efficacy and safety of prolonged therapy with low-dose clarithromycin in patients with chronic rhinosinusitis with polyps (CRSwP) after endoscopic sinus surgery (ESS). A total of 10 patients with CRSwP were identified and subjected to bilateral ESS. In post-operative patients they were treated with nasal wash with saline solution and steroid sprays (beclomethasone). During follow-up, after 30–40 days after the operation (M = 35.4 SD = +4.33), patients reported a worsening of symptoms with onset of nasal obstruction; reduction/loss of smell; headache; onset of viscous secretions and therefore all patients continued therapy with saline nasal irrigation, topical steroid therapy and started macrolide (clarithromycin 500 mg/pill: 1 pill/day for 3 days a week for 1 month). 22-item SinoNasal Outcome Test (SNOT-22) and a score to the endoscopic evaluation (endoscopic appearance score, EAS) before and after treatment were performed to evaluate efficacy of treatment. The results of the SNOT-22 and EAS showed statistically significant improvements (p

Background and purpose Sphingosine-1-phosphate (S1P) has been shown to be involved in the asthmatic disease as well in preclinical mouse experimental models of this disease. The aim of this study was to understand the mechanism(s) underlying S1P effects on the lung. Experimental approach BALB/c, mast cell-deficient and Nude mice were injected with S1P (s.c.) on days 0 and 7. Functional, molecular and cellular studies were performed. Key results S1P administration to BALB/c mice increased airway smooth muscle reactivity, mucus production, PGD2 , IgE, IL-4 and IL-13 release. These features were associated to a higher recruitment of mast cells to the lung. Mast cell-deficient Kit (W) (-sh/) (W) (-sh) mice injected with S1P did not display airway smooth muscle hyper-reactivity. However, lung inflammation and IgE production were still present. Treatment in vivo with the anti-CD23 antibody B3B4, which blocks IgE production, inhibited both S1P-induced airway smooth muscle reactivity in vitro and lung inflammation. S1P administration to Nude mice did not elicit airway smooth muscle hyper-reactivity and lung inflammation. Naive (untreated) mice subjected to the adoptive transfer of CD4+ T-cells harvested from S1P-treated mice presented all the features elicited by S1P in the lung. Conclusions and implications S1P triggers a cascade of events that sequentially involves T-cells, IgE and mast cells reproducing several asthma-like features. This model may represent a useful tool for defining the role of S1P in the mechanism of action of currently-used drugs as well as in the development of new therapeutic approaches for asthma-like diseases.

Human endogenous retroviruses (HERVs) have been implicated in human physiology and in human pathology. A better knowledge of the retroviral transcriptional activity in the general population and during the life span would greatly help the debate on its pathologic potential. The transcriptional activity of four HERV families (H, K, W, and E) was assessed, by qualitative and quantitative PCR, in PBMCs from 261 individuals aged from 1 to 80 years. Our results show that HERV-H, HERV-K, and HERV-W, but not HERV-E, are transcriptionally active in the test population already in the early childhood. In addition, the transcriptional levels of HERV-H, HERV-K, and HERV-W change significantly during the life span, albeit with distinct patterns. Our results, reinforce the hypothesis of a physiological correlation between HERVs activity and the different stages of life in humans. Studies aiming at identifying the factors, which are responsible for these changes during the individual’s life, are still needed. Although the observed phenomena are presumably subjected to great variability, the basal transcriptional activity of each individual, also depending on the different ages of life, must be carefully considered in all the studies involving HERVs as causative agents of disease.

The work at hand illustrates the design approach adopted for a large strain sensor, based on the carbon nanotube (CNT) technology, devoted to operations of structural health monitoring and shape reconstruction. After a critical discussion on the specifications, the most suited materials and processes were selected, with specific focus on the dispersion and deposition strategies. Then, by means of a FE approach, the topology in terms of CNT volume concentration, morphology (curvature) and orientation, was identified. A feasibility study on the manufacturability was then carried out. Finally, in compliance with the initial specifications, the set of calibration and space qualification tests was illustrated. The above mentioned activities were developed within the Project “Graphene-Polymeric Spray Sensor for Shape Recognition of Super-Deformable Structures”, GRAPSS, sponsored by CIRA within the “Curiosity Driven” initiative.

Discusses the technologies and applications supported by nanotechnology, considered one of the 21st century's most promising technologies. Nanotechnology deals with the design, development, and manipulation of materials and devices with at least one dimension sized on a nanometer scale. It involves fields of science as diverse as surface science, organic chemistry, molecular biology, semiconductor physics, microfabrication, with a vast range of applications, such as in medicine, electronics, biomaterials, and energy production. Its ultimate goal is to be able to predictably design, construct, and control nanosystems, tailoring them to specified needs.

Purpose: Implant impressions and working models form integratedprecision systems for registration and transmission of clinical data.The components of implant systems have a dimensional tolerancecapable of introducing inaccuracies in the impression, thus in theprostheticframework.Thisarticleaimedatcomparing2repositioningimpression techniques: one using impression copings (conventionaltechnique) and the other using the final abutments as impressioncopings (interceptive technique).Materials andMethods: Two experimentalmodels, onewith 4 par-allel implants and the other with 4 nonparallel implants, were usedto make silicone impressions. Twenty impressions were made withthe conventional technique, and a further 20 were made with theinterceptive technique. Three-dimensional images acquired with athree-dimensional scanner were measured using a three-dimensionalimage analysis software, comparing models obtained from theimpressions with the experimental models. Data were statisticallyanalyzed by means of confidence intervals calculated with themean (α = 0.05), descriptive (box plot), and bivariate analyses.Results: Statistic analysishighlighted significant differences amongmodels obtained using both techniques: the interceptive techniquegenerated working models with less distortion and variability.Conclusions: For internal-connection implants, the interceptivetechnique provided significantly more precise working models thandid the conventional technique.Key Words: Implant prosthesis, impression technique, precision,interceptive impression, internal connection(J Craniofac Surg 2014;25: 822–827)

The canonical arm of NF-κB signaling is well studied in Inflammatory Bowel Disease (IBD) while its noncanonical counterpart has yet to be fully defined. The activation of the noncanonical pathway initiates the nuclear transcription of chemokines associated with chronic inflammation and other diverse immunological processes. Infliximab is an effective anti-TNF treatment that reduces inflammation in IBD, yet a significant percentage of patients are unresponsive or lose responsiveness. Here, we show that noncanonical NF-κB signaling has more relevant implications on IBD and its expression levels correlate to infliximab responsiveness. Our study evaluated noncanonical NF-κB signaling in 27 IBD patient and 9 non-IBD control patient tissue biopsies. Data from these studies were analyzed using bioinformatics to predict its influence on cellular pathways. Genes related to the noncanonical NF-κB pathway were significantly upregulated in IBD lesions compared to healthy tissue. IBD patients that positively respond to infliximab had significantly decreased expression levels compared to nonresponsive patients. These results suggest infliximab, when effective, decreases noncanonical signaling to lessen inflammation. Through targeting in part, the noncanonical NF-κB pathway has prominent emerging roles in IBD pathobiology and is an indicator for improving drug efficacy.

The identification and surveillance of patients with liver dysfunctions and the discovering of new disease biomarkers are needed in the clinical practice. The aim of this study was to investigate on Survivin-immunoglobulin (Ig)M immune complex (IC) as a potential biomarker of chronic liver diseases.Serum levels of Survivin-IgM were measured using an enzyme-linked immunoassay that had been standardized and validated in our laboratory in 262 individuals, including healthy subjects and patients with chronic viral hepatitis, cirrhosis and hepatocellular carcinoma (HCC).Survivin-IgM IC was lower in healthy subjects (median, 99.39 AU/mL) than in patients with chronic viral hepatitis (median, 148.03 AU/mL; P = 0.002) or with cirrhosis (median, 371.00 AU/mL; P 0.001). Among patients with cirrhosis, those with hepatitis C virus (HCV) infection showed the highest level of Survivin-IgM IC (median, 633.71 AU/mL; P 0.001). The receiver-operator curve analysis revealed that Survivin-IgM accurately distinguishes HCV correlated cirrhosis from chronic viral hepatitis (area under the curve [AUC], 0.738; sensitivity, 74.5%; specificity, 70.7%). A multivariate logistic regression model, including Survivin-IgM IC, aspartate aminotransferase (AST) and AST/alanine aminotransferase (ALT) ratio increased the prediction accuracy for the identification of the cirrhotic HCV patients (AUC, 0.818; sensitivity, 87.2%; specificity, 65.9%). Conversely, Survivin-IgM IC significantly decreased in HCC patients (median, 165.72 AU/mL; P = 0.022).Our results suggest that Survivin-IgM immune complex may be used as a potential biomarker for liver damage, particularly for the identification of the HCV-related cirrhotic population.

The most commonly used parameter for monitoring LV function with echocardiography is LV ejection fraction (LVEF). LVEF itself and LVEF drop during and after cancer treatment are currently used to define the onset cardiotoxicity. New, normal cutoff points of LVEF (≥52% in men and ≥54 in women) have been recently established. Changes in LVEF indicative of LV damage can be more appropriately identified when comparisons are made between baseline and follow-up studies. ASE/EACVI recommendations on the use of cardiac imaging in cancer patients fix the drop of LVEF of at least 10 points to an LVEF

Since it was first identified, thymosin alpha 1 (Tα1) has been characterized to have pleiotropic effects on several pathological conditions, in particular as a modulator of immune response and inflammation. Several properties exerted by Tα1 may be attributable to a direct action on lymphoid cells. Tα1 has been shown to exert an immune modulatory activity on both T cell and natural killer cell maturation and to have an effect on functions of mature lymphocytes, including stimulating cytokine production and cytotoxic T lymphocyte-mediated cytotoxic responses. In previous studies we have shown that Tα1 increases the expression of major histocompatibility complex class I surface molecules in murine and human tumor cell lines and in primary cultures of human macrophages. In the present paper, we describe preliminary data indicating that Tα1 is also capable of increasing the expression of tumor antigens in both experimental and human tumor cell lines. This effect, which is exerted at the level of the target tumor cells, represents an additional factor increasing the antitumor activity of Tα1.

Nanotechnology deals with the design, development, and manipulation of materials and devices with at least one dimension sized on a nanometer scale. It involves fields of science as diverse as surface science, organic chemistry, molecular biology, semiconductor physics, microfabrication, with a vast range of applications, such as in medicine, electronics, biomaterials, and energy production. Its ultimate goal is to be able to predictably design, construct, and control nanosystems, tailoring them to specified needs. This is the classical task of engineers, requiring a quantitative modeling of the problem of interest, detailed and accurate enough to make a reliable design possible. In the case of the applications to biology and medicine, living bodies are seen by nanotechnologists as the (essentially passive) environment in which the nanosystems perform their tasks. This modelization does not take into account the actual nature of living beings, which has been uncovered piece by piece in a long process, converging in the last 50 years to form a unified picture, which can be conveyed by a simple sentence: living organisms are hierarchically integrated sets of nanomachines. This may be clear to biologists, they lack reliable methodological and theoretical tools that allow the generalization of their findings into quantitative models, suited to a design procedure. Filling this gap would allow the engineering of biosystems at the nanometric scale, which has the potential of revolutionizing both nanotechnologies and biotechnologies. This article is an attempt to give an idea of this scenario from the engineering point of view, putting in perspective the problems and challenges, and giving an idea of the possible developments and their implications.

Particles generated by combustion comprise sub-100 nm soot particles that are often associated with adverse health effects such as asthma and cardiovascular diseases as well as lung carcer mortality. Little is known about inflammatory processes generated by combustion nanoparticles that may underlie acute and chronic airway dysfunctions. In this study, preliminary results of the effect of sub-100 nm particles on macrophages, which are involved in innate immune responses responsible of inflammation, are presented. Samples were prepared starting from collection of soot particles from fuel-rich ethylene flames by means of a vertical probe and a quartz plate. Particles collected on filters were successively dissolved in water with the help of a surfactant (dimethyl sulfoxide) and sonication for 48h to obtain a stable and homogeneous dispersion. To evaluate the molecular mechanism underlying soot particle cytotoxic activities, we used murine macrophages (J774.1 cells) and treated them with particles (dissolved in DMSO 10%; 1pg/ml-5ng/ml) for 5 hours. Cell-free supernatant was tested for the levels of IL-1? and IL-1? by means of ELISA. The administration of the sole soot particles on J774.1 cells induced a concentration-dependent release of IL-1? and IL-1?, pro-inflammatory cytokines. This effect was not associated to cell death because the addition of necrostatin (1uM), well-known necrosis inhibitor, did not alter the levels of the proinflammatory cytokines. Surprisingly, the co-administration of soot particles with lipolysaccharide (LPS), well-known pro-inflammatory insult, led to the release of IL-1? and IL-1? in an additive manner compared to the sole LPS or soot particles, implying the synergistic activities of both pro-inflammatory stimuli. Our data suggest that very low concentrations of soot particles lead to the initiation of an inflammatory process that underlies IL-1? and IL-1? release. The co-administration of LPS and soot particles further exacerbates the release of the pro-inflammatory cytokines, explaining the higher susceptibility of patients to inflammatory-based airway diseases once exposed to air pollution.

The aim of the present microleakage study was to assess the sealing ability of nanohybrid composite crowns with different finish lines exposed to simulated mechanical periodontal treatment (SMPT).After sample size calculation (α=0.05; β=0.20; δ=1.0; σ=0.8), sixty extracted mandibular molars were divided into four groups (N.=15): G1, 90° shoulder; G2, beveled 90° shoulder; G3, 90° shoulder and SMPT; G4, beveled 90° shoulder and SMPT. Tooth preparations were carried out by means of diamond burs and Arkansas stones. The buildup of crowns was performed with a nanohybrid composite on master casts obtained after polyether impressions and crowns were cemented with self-adhesive cement. Groups G3 and G4 were subjected to the equivalent of five years of semestral mechanical periodontal scaling with Gracey curettes (2-mm long strokes, 5 N). Samples were immersed into a methylene blue supersaturated solution for 10 minutes. Microleakage was measured by stereomicroscopic observation of multiple sections of the samples and leakage data underwent statistical analysis with non-parametric tests.Marginal microleakage was 1.53±1.27% and 17.60±12.72% of the length of the adhesive interface in G1 and G2, respectively. SMPT reduced dye penetration (P0.001) with G3 not leaking at all and G4 leaking along the 5.58±1.84% of the adhesive interface. The bevel preparation significantly worsened the marginal seal both in control and treated crowns (P0.001).Microleakage of nanohybrid composite crowns increased by adding a bevel to a 90° shoulder preparation and diminished after SMPT.

Objectives: The present prospective clinical study aimed at evaluating the clinical perfomances of tooth-supported 3-unit posterior zirconia FDPs after 8 years of service. Methods: Thirty-seven patients received 48 3-unit zirconia-based (Procera, NobelBiocare) FDPs. The prostheses replaced either a premolar or a molar. Specific inclusion criteria were used. Standardized tooth preparations were realized: 2mm occlusal reduction, 1.5mm axial reduction and circumferential chamfer shoulder placed 0.5 mm subgingivally buccally and supragingivally lingually on sound tooth structure; all internal angles were rounded. Impressions were made with polyethers (3M ESPE). CAD-CAM frameworks (Procera, NobelBiocare) with 9mm2 connector and 0.6mm retainer were made. The restorations were luted using a resin cement (RelyXUnicem, 3M ESPE). The patients were recalled after 1, 6 and 12 months after the cementation and then annually for a whole observational period of 8 years. Survival and success of the veneering ceramic and zirconia were assessed. The esthetic and technical outcomes were rated using the USPHS criteria. The biologic outcomes were analyzed at abutment and contralateral teeth. Descriptive statistics were performed (Kaplan-Meier, Wilcoxon). Results: All FDPs completed the study, resulting in 100% cumulative survival rate and 93.75% cumulative success rate. No losses of retention were recorded. Forty restorations were rated Alpha in all measured parameters. Minor chipping of ceramics was detected in 3 restorations. Four restorations were rated Bravo for marginal integrity at 8 years. No significant differences between the periodontal parameters of the test and control teeth were observed. As to esthetics, 42 restorations were rated Alpha and 6 were rated Bravo by both the clinicians and the patients at the 8-year follow-up. Conclusions: Eight-year clinical results showed that posterior 3-unit zirconia-based FDPs can be considered a viable treatment option in the medium-term. These restorations may be considered reliable to replace a posterior missing tooth.

Hepatitis C virus core antigen (HCVcoreAg) may be measured in serum with a sensitive, recently validated assay. Beyond its value as a marker of viral infection, there are little data on its relation with clinical, histological, and virological parameters. In this study, the significance of HCVcoreAg levels was studied in a prospective cohort of 114 patients with chronic hepatitis C. HCVcoreAg was measured by a commercial chemiluminescent microparticle immunoassay. Clinical and virological data included quantitative HCV-RNA, HCV genotype, ALT, GGT, IL28B rs12979860 polymorphism as well as liver histology parameters. HCVcoreAg levels were correlated significantly with HCV-RNA (r=0.56; P

WOS: 000350546100004, PubMed ID: 24661203, The ability to get and keep an erection is important to men for several reasons and the inability is known as erectile dysfunction (ED). ED has started to be accepted as an early indicator of systemic endothelial dysfunction and subsequently of cardiovascular diseases. The role of NO in endothelial relaxation and erectile function is well accepted. The discovery of NO as a small signalling gasotransmitter led to the investigation of the role of other endogenously derived gases, carbon monoxide (CO) and hydrogen sulphide (H2S) in physiological and pathophysiological conditions. The role of NO and CO in sexual function and dysfunction has been investigated more extensively and, recently, the involvement of H2S in erectile function has also been confirmed. In this review, we focus on the role of these three sister gasotransmitters in the physiology, pharmacology and pathophysiology of sexual function in man, specifically erectile function. We have also reviewed the role of soluble guanylyl cyclase/cGMP pathway as a common target of these gasotransmitters. Several studies have proposed alternative therapies targeting different mechanisms in addition to PDE-5 inhibition for ED treatment, since some patients do not respond to these drugs. This review highlights complementary and possible coordinated roles for these mediators and treatments targeting these gasotransmitters in erectile function/ED. Linked ArticlesThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit, Turkish Academia Young investigator award programmeTurkish Academy of Sciences; TUBA-GebipTurkish Academy of Sciences; Turkish Scientific Research Council TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S453, 109S432]; EBILTEMEge University; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; CNPqNational Council for Scientific and Technological Development (CNPq); Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina; FAPESC; COST actionEuropean Cooperation in Science and Technology (COST) [BM1005], The authors would like to thank the financial supports by Turkish Academia Young investigator award programme; TUBA-Gebip (to G. Y. A.), Turkish Scientific Research Council TUBITAK for the grant #109S453 and # 109S432 (to G. Y. A.), EBILTEM (to G. Y. A.), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; CNPq (to A. E. L.) and Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina; FAPESC (to A. E. L.) and the COST action BM1005 (ENOG: European Network on Gasotransmitters).

Objectives: This 3D-FEA aimed at evaluating the biomechanical response of bone and implant-supported prostheses in the presence of axial and tilted implants. Methods: Four numerical models of human mandible with different implant-supported prostheses configurations were set up. The cortical bone was considered orthotropic according to an indipendent mechanical characterization performed on fresh human dentate mandibles. Jaw-closing muscular forces were simulated. The spongy bone was considered isotropic while the temporo-mandibular disc was considered hyperelastic. Contact pairs elements were generated at the fixture-bone interfaces. Failure criteria were based on ultimate normal and shear stresses computed in in vivo. The strain fields in the periimplant bone were compared to Frost's biomechanical relation. The bone remodelling stimuli were computed as the strain energy density variations. Results: EPTO1=FIRST PRINCIPAL STRAIN EPTO3=THIRD PRINCIPAL STRAIN STRAIGHT IMPLANTS. PERI-IMPLANT STRAIN FIELDS. POSTERIOR IMPLANTS, EPTO1 2000 TO 8000, EPTO3 -1500 TO -8000. ANTERIOR IMPLANT, EPTO1 667 TO 4667, EPTO3 -667 TO -3340. STRAIN STATE ON EXTERIOR CORTEX BETWEEN IMPLANTS, EPTO1 100 TO 1000, EPTO 3 -100 TO -1000. STRAIN STATE IN SPONGY BONE BETWEEN IMPLANTS, EPTO1 100 TO 500, EPTO3 -100 TO -500. TILTED IMPLANTS. PERI-IMPLANT STRAIN FIELDS. POSTERIOR IMPLANTS, EPTO1 333 TO 4330, EPTO3 -667 TO -3333. ANTERIOR IMPLANT, COMPARABLE TO STRAIGHT CONFIGURATION. STRAIN STATE ON EXTERIOR CORTEX BETWEEN IMPLANTS, COMPARALE TO STREISHT CONFIGURATION. STRAIN STATE IN SPONGY BONE BETWEEN IMPLANTS, COMPARABLE TO STRAIGHT CONFIGURATION. Conclusions: Bone strain fields were scarcely influenced by implant orientation but significantly influenced by the rigidity of the restorative material.