Evolution of echocardiographic and cardiac magnetic resonance imaging abnormalities during follow-up in patients with multisystem inflammatory syndrome in children.

AIMS: Multisystem inflammatory syndrome in children (MIS-C) with cardiovascular manifestations are frequent. However, there is lacking evidence regarding cardiological follow-up of this cohort of patients. The aim of our study was to describe the early and mid-term cardiac abnormalities assessed by standard and speckle-tracking echocardiography (STE), and cardiac MRI (CMR). METHODS AND RESULTS: We enrolled 32 patients (21 male, 11 female), mean age 8.25 ± 4years, with diagnosis of MIS-C. During admission, all children underwent TTE, STE with analysis of left ventricle global longitudinal strain (GLS) and CMR. Patients underwent cardiological evaluation at 2 (T1) and 6 months (T2) after discharge. Cardiac MRI was repeated at 6 months after discharge. Mean left ventricular ejection fraction (LVEF) at baseline was 58.8 ± 10% with 10 patients (31%) below 55%. Speckle-tracking echocardiography showed reduced mean LV GLS (-17.4 ± 4%). On CMR, late gadolinium enhancement (LGE) with non-ischaemic pattern was evident in 8 of 23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 ± 7.5 vs. 58.8 ± 10.6%, P-value 0.044) with only three patients (10%) below ≤ 55% at T1. Left ventricular (LV) GLS remained impaired at T1 (-17.2 ± 2.7 vs.-17.4 ± 4, P-value 0.71) and significantly improved at T2 (-19 ± 2.6% vs. -17.4 ± 4%, P-value 0.009). LV GLS was impaired (>-18%) in 53% of patients at baseline and T1, whereas only 13% showed persistent LV GLS reduction at T2. Follow-up CMR showed LGE persistence in 33.4% of cases. CONCLUSION: Early cardiac involvement significantly improves during follow-up of MIS-C patients. However, subclinical myocardial dysfunction seems to be still detectable after 6 months of follow-up in a not negligible proportion of them.

Clinical Performance of Complete-Arch Implant- Supported Rehabilitations Using Monolithic Lithium Disilicate Restorations Bonded to CAD/CAM Titanium and Zirconia Frameworks up to 5 Years.

This clinical study evaluated the survival of monolithic lithium disilicate (ML) (IPS Emax, Ivoclar Vivadent) restorations bonded to complete-arch CAD/CAM made titanium or zirconia frameworks. Between August 2007 and December 2009, 15 patients (7 female, 8 male; mean age: 56.8 years old) received 30 implant-supported screw-retained rehabilitations with ML restorations cemented to CAD/CAM made titanium (T) (n=6) or zirconia (Z) frameworks (n=24) adhesively (Multilink Automix, RelyX Unicem) and followed up until December 2015. The evaluation protocol involved technical failures (chipping, debonding or fracture of crown/framework, screw loosening), Californian Dental Association (CDA) quality criteria (Romeo: Excellent; Sierra: Acceptable; Tango: Retrievable; Victor: Not acceptable) and biological failures (mucositis, peri-implantitis). Mean observation time was 60.3 months. No implants were lost, and all the prostheses were in situ. Four mechanical failures occurred in the form of minor chipping (n=3 in ML-Z, n=1 in ML-T) and major fracture in ML crown (n=1 in ML-Z). Romeo scores (N=370) decreased until final observation (N=347) and 23 Sierra scores were given to the restorations. Mucositis was observed in 3 patients and peri-implantitis in one patient. Complete-arch implant-borne FDPs made of monolithic lithium disilicate bonded to titanium or zirconia frameworks could be a promising alternative.

Gut T cell-independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells.

The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through nonredundant T cell-dependent (TD) and T cell-independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria, and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here, we show that the intestinal TI pathway required CD40-independent B cell-activating signals from TACI, a receptor for the innate CD40 ligand-like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria-specific SIgA responses through an intestinal TI program.

Reliability of Chair-side Monolithic CAD-CAM Generated Lithium Disilicate Single Crowns with Knife- Edge Finish Line: Up to 5-Year Retrospective Analysis of Clinical Performance.

This clinical study evaluated the survival of monolithic lithium disilicate (MLD) single crowns. Between January-2010 and January-2015, 87 patients received 122 MLD (IPS e.max CAD) single crowns on natural teeth with knife-edge finish lines that were adhesively bonded (Maxcem Elite). MLD single crowns (N=122) were bonded on 60 molars (maxilla:35, mandible:25), 53 premolars (maxilla:27, mandible:26), 4 canines (maxilla:2, mandible:2), 3 laterals and 2 centrals (maxilla). One crown fracture, one retention loss and one endodontic complication were experienced (survival rate: 97.5%). MLD single crowns could be safely indicated on teeth with knife-edge preparations.

Phytochemical fingerprint and chemometrics for natural food preparation pattern recognition: an innovative technique in food supplement quality control.

Recently, the fingerprint approach using chromatography has become one of the most effective tools for quality assessment of herbal medicines and food supplements: due to the complexity of the chromatographic fingerprint and the irreproducibility of chromatographic instruments and experimental conditions, chemometric approach is employed to deal with the chromatographic fingerprint. The study was aimed at developing new analytical methods for the multivariate phytochemical fingerprinting of bioactive compounds in eight tree-species bud-preparations, commonly used in phytotherapy. Methods was used to identify and quantify the main bioactive compounds (polyphenols, organic acids and vitamins), and obtain a specific botanical profile in order to assess the contribution of each single bioactive class to the total bud preparation phytocomplex. A chemometric approach was used to distinguish among different genotypes assuring the identity, safety and quality of the botanical raw materials. The established protocol was simple, sensitive and reliable and it could be used for the evaluation and quality control of bud-extracts and natural food supplements: the proposed method was successfully applied to the characterization of commercial bud-preparations, demonstrating to be an effective tool for the fingerprinting of this plant material. The new approach developed in this study represents a good alternative for improving the classification results of herbal materials with complex chromatograms. It should be necessary to develop a "multivariate chromatographic fingerprint", in order to differentiate the herbal preparations according to their genotype, avoiding substitutions, changes or adulterations with other species or synthetic drugs.

Responsive population dynamics and wide seeding into the duodenal lamina propria of transglutaminase-2-specific plasma cells in celiac disease.

A hallmark of celiac disease is autoantibodies to transglutaminase 2 (TG2). By visualizing TG2-specific antibodies by antigen staining of affected gut tissue, we identified TG2-specific plasma cells in the lamina propria as well as antibodies in the subepithelial layer, inside the epithelium, and at the brush border. The frequency of TG2-specific plasma cells were found not to correlate with serum antibody titers, suggesting that antibody production at other sites may contribute to serum antibody levels. Upon commencement of a gluten-free diet, the frequency of TG2-specific plasma cells in the lesion dropped dramatically within 6 months, yet some cells remained. The frequency of TG2-specific plasma cells in the celiac lesion is thus dynamically regulated in response to gluten exposure. Laser microdissection of plasma cell patches, followed by antibody gene sequencing, demonstrated that clonal cells were seeded in distinct areas of the mucosa. This was confirmed by immunoglobulin heavy chain repertoire analysis of plasma cells isolated from individual biopsies of two untreated patients, both for TG2-specific and non-TG2-specific cells. Our results shed new light on the processes underlying the B-cell response in celiac disease, and the approach of staining for antigen-specific antibodies should be applicable to other antibody-mediated diseases.

Serviceberry, a berry fruit with growing interest of industry: Physicochemical and quali-quantitative health-related compound characterisation.

Amelanchier canadensis (L.) Medik., commonly called serviceberry, is a potential functional food that is also used for its medicinal purposes. This work evaluated the potential of a cultivated serviceberry species as a functional food by characterising its physicochemical characteristics, antioxidant capacity, vitamin C, phenolics and other phytochemicals selected as health-promoting biomarkers, using high-performance liquid chromatography. The most important compound class identified was polyphenols (62.10%), followed by organic acids (22.63%), monoterpenes (7.95%), and vitamins (7.32%). Results showed that serviceberry fruits could be good sources of phenolic constituents, as catechins (343.46 ± 29.46 mg/100 gFW), anthocyanins (220.66 ± 17.43 mg/100 gFW), and tannins (209.29 ± 7.81 mg/100 gFW) (FW = fresh weight). These results highlight the potential role of A. canadensis fruits as a functional food. Further studies are needed to identify several genotypes for breeding to get suitable cultivars for fresh consumption and processing.

The success of indirect restorations in posterior teeth: a systematic review of the literature.

AIM: Aim of the study was to evaluate the long-term reliability and effectiveness of inlays and onlays in ceramic and composite material, examining scientific studies published from 2004 to 2013. The results of this review were analyzed and compared with the important literature review proposed by Manhart in 2004. METHODS: With this review it was possible to analyze a total sample of 5858 Class I and II restorations, made in the posterior region: 5295 ceramic and 563 composite restorations in 2377 patients. Works were evaluated using USPHS, modified USPHS and CDA criteria after a mean observation period of 5.4 years (5.9 years for ceramic restorations, 2.6 for composite restorations). RESULTS: The arithmetic average of success was 94%, higher in ceramic restorations (94.9%) than composite materials (91.1%). The weighted average success rate was 95.3%, 92.8% for composite restorations and 96.3% for ceramic ones. The highest rates of success were found in ceramic restorations notwithstanding the longer observation period. CONCLUSION: Indirect restorations have a low failure rate and they prove to be an excellent choice in the treatment of both class I and II lesions. During the last 6 years, the parameters related to these restorations have improved, with a 4% increase of success.

Botanicals in Ribes nigrum bud-preparations: an analytical fingerprinting to evaluate the bioactive contribution to total phytocomplex.

UNLABELLED: CONTEXT. Ribes nigrum L. (Grossulariaceae) is among the most commonly used herbal medicines and it is popularized for its alleged tonic effect and curative and restorative properties. The current practice of identifying herbal extracts is by measuring the concentration of the main botanicals. Their concentrations are used to characterize the herbal preparations and fingerprinting is recommended by the main Pharmacopeias as a potential and reliable strategy for the quality control of complex mixtures. OBJECTIVE: The aim of this research was to perform an analytical study of R. nigrum bud-preparations, in order to identify and quantify the main bioactive compounds, obtaining a specific chemical fingerprint to evaluate the single class contribution to herbal preparation phytocomplex. MATERIALS AND METHODS: The same analyses were performed using a high-performance liquid chromatograph-diode array detector both on University lab preparations and on commercial preparations from different Italian locations. Different chromatographic methods were used to analyse the macerated samples, two for polyphenols and one for terpenic compounds. RESULTS. Ribes nigrum was identified as a rich source of anti-inflammatory and antioxidant compounds. The observed analytical firgerprint demonstrated that these bud-preparations represent a rich source of terpenic and polyphenolic compounds, especially catechins and phenolic acids. DISCUSSION AND CONCLUSION: Analytical fingerprinting could be an important tool to study the assessment of chemical composition and bioactivities of plant-derived products, helping to find new sources of natural health-promoting compounds: this study allowed the development of an effective tool for quality control through botanical fingerprinting of bud preparations.

Polymerization degree and cementation methods of two different self-adhesive luting cements used for glass fiber postcementation.

AIM: Aim of this study was to evaluate two different luting cements and how their clinical procedures influence the postcementation quality. METHODS: Thirty-six freshly extracted mono-radicular teeth (N.=18) were treated endodontically and randomly divided into two groups. Posts were cemented respectively with two different self adhesive luting cements: Group A - RelyX Unicem (3M Espe) and Group B - Multilink Sprint (Ivoclar-Vivadent) following the manufacturers' instructions. Teeth were then thermocycled according to protocol ISO/TR 11405 and were immersed 24 hours in 2% methylene-blue solution. Each tooth was sectioned by a diamond-coated saw (Isomet-Buhler) from CEJ to apex. Each slice was examined for the presence or absence of gutta-percha remnants, voids, bubbles, dye infiltration degree and polymerization grade of the luting agent. Findings were evidenced by stereoscopic microscopy (30x) and Micro-Raman spectroscopy. Mann-Whitney and ANOVA statistical analyses were performed for all results. RESULTS: No statistical significances were evidenced for gutta-percha presence, dye infiltration and polymerization degree. Voids were present mostly in Group B and bubbles in Group A. Both differences were statistically significant. CONCLUSION: Materials and protocols for glass fiber posts cementation are fundamental for the clinical success. Self adhesive luting cements, if used correctly, could be an acceptable and quick luting agent for postcementation.

A combination therapy to treat second-degree anti-Ro/La-related congenital heart block: a strategy to avoid stable third-degree heart block?

While mainly based on the use of fluorinated steroids, there is no standard management of anti-Ro/La-related congenital heart block (CHB). This is a report concerning two consecutive cases of anti-Ro/La-related second-degree block treated with betamethasone (4 mg/day), weekly plasmapheresis, and intravenous immunoglobulins (IVIGs; 1 g/kg) administered every 15 days, a therapy that was begun shortly after CHB was detected and continued until delivery. The newborns were also treated with IVIG (1 g/kg) soon after birth and continued fortnightly until the anti-Ro/La antibody levels became undetectable. In both cases second-degree AV block reverted to a stable sinus rhythm with a first-degree atrioventricular (AV) block. Moreover, there was no recurrence of CHB when therapy was suspended, as confirmed by a 29 month and an eight month follow-up, respectively.

Prophylometric and SEM analyses of four different finishing methods.

Adhesion is the pivot of the modern restorative dentistry. Inlays, onlays and veneers have become a valid alternative to the traditional prosthetic treatments even in the rehabilitation of extremely damaged teeth, allowing a consistent saving of sound tooth tissues. Composite resins and dental adhesive are continously investigated and improved, nevertheless the optimization of the tooth-adhesive interface has to be considered: in fact, the long-term stability of adhesion between tooth and composite material depends on the treatment of the amelo-dentinal surfaces. THIS STUDY INVESTIGATED THE QUALITY OF THE OCCLUSAL WALLS OF A CAVITY PREPARED TO RECEIVE AN INLAY AND FINISHED WITH FOUR DIFFERENT SYSTEMS: thin and extra-thin diamond coated burs, a 12-blades carbide burs and a diamond-coated tip driven by sonic instrument. Consequently, prophylometric and SEM analyses were performed on the samples. The average roughness values recorded by the prophylometer were expressed by the parameters Ra and RZ: there is a correspondence between the numeric values and the pictures of the SEM. The results show a better quality (low roughness values) of the surface treated with multi-blade burs, followed by the this and extra-thin diamond coated burs. The 25 micron diamond-coated tip of the sonic instrument obtains the roughest surface and a sensibly higher amount of smear layer than the other tested systems.

Indirect resin composite restorations: evaluation of polymerization of luting agents by means of micro-Raman spectrophotometry.

AIM: The degree of conversion of a luting composite cement influences its clinical performance. Aim of the study was to evaluate the degree of conversion of 4 different composite cements by means of micro Raman spectrophotometry. METHODS: Forty-four cylindrical onlays of different and defined thickness (1, 2, 3, 4 mm) were built using a custom made template. The onlays were made in composite material (Signum, Heraeus; shade A 3,5) and cemented onto a glass plate with different luting materials: dual curing (Variolink II, Calibra) and light curing (Venus flow, Tetric flow). The lamp tip was shielded in order to have the light reach the cement only through the onlay. Samples were divided into 12 groups (N.=3), differing in onlay thickness and luting material. Each sample was examined in three spots by a micro-Raman spectrophotometer (Dilor Hr-Labram). The conversion degree was evaluated by analyzing the variations in intensity of the 1638 cm(-1) aliphatic peak (C=C), characteristic of all Bis-GMA containing materials, related to the invariant 1608 cm(-1) (C-C of the aromatic ring). RESULTS: All materials show good polymerisation results below 1 mm and 2 mm onlays. Below onlays thicker than 3 mm a constant degree of conversion throughout the surface of samples could not be found: spots with satisfactory polymerisation and spots with insufficient polymerisation were found. CONCLUSIONS: Onlay thickness has a key role in cement conversion. The thicker the onlay, the less predictable the conversion.

Location, location, location: B-cell differentiation in the gut lamina propria.

The intestinal immune system includes an immunoglobulin (Ig)A-inductive site represented by Peyer's patches (PPs) and an IgA effector site represented by the lamina propria (LP). This canonical map of intestinal IgA production has been blurred recently by studies showing the presence of active IgA class switching in the LP. Here we discuss the functional implications and controversial nature of these findings.

A new miniaturised optical system for chemical species spectroscopic detection based on a scanning integrated Mach-Zehnder microinterferometer on LiNbO3.

Absorption or emission spectroscopy is a powerful tool for detecting chemical compounds, diluted in fluid media: the sensitivity of this technique depends on the optical path of the source radiation, on the spectral window used for analysis and on the spectrometer performances. In this view, we designed and produced the first prototypes of an integrated scanning Fourier Transform Microinterferometer with Mach-Zehnder geometry, by using MEOS (Micro Electro Optical Systems) technologies. The microdevice, obtained by fabricating integrated optical waveguides on LiNbO(3) (LN) crystals, is electrically driven, without moving parts, by exploiting the electrooptical properties of the material. The microdevice operates the Fourier Transform of the input radiation spectral distribution, which can be reconstructed starting from the output signal by means of Fast Fourier Transform (FFT) techniques. The microinterferometer weights few grams, the power consumption is of a few mW and, in principle, can operate in the LN transmittance range (0.36-4.5 microm). The microinterferometer performances were preliminary tested in the (0.4-1.7 microm) spectral window. In the Visible region (0.4-0.7 mum) this microsystem demonstrated a spectral resolution suitable for detecting the characteristic lines of the solar spectrum together with the absorption bands of common gases present in Earth's atmosphere. In a further experiment we tested its performances for gas trace detection by using a calibrated NO(2) optical gas cell, showing the possibility to reveal up to 10 ppb, when suitable optical paths are used. Finally, colorimetry tests for the titration of an organic dye (E131) in alcohol solution are presented.

A 24-month survey on root canal treatment performed by NiTi engine driven files and warm gutta-percha filling associated system.

AIM: Techniques based on NiTi engine driven files for shaping and warm gutta percha for obturing the root canal space are becoming more and more popular. Aim of this paper is to evaluate, by a clinical longitudinal study, the type of sealing and the outcome of endodontic treatment, performed by new Profile and Thermafil technique, in teeth with or without periapical lesions. METHODS: A total of 122 teeth in 64 patients were consecutively enrolled in the study; 63 teeth had normal periapical status (Group A) and 59 teeth had periapical lesion (Group B). Endodontic therapy was carried out by Profile .04 and Profile .06 NiTi engine driven files and the obturation was made by Thermafil, a filling technique based on heated gutta-percha surrounding a plastic carrier. The type of sealing was evaluated by a score (A best - D worst) and the type of healing was classified as complete, incomplete and failure according to previous published data. The radiographical outcome of the teeth was evaluated by independent observers after 24 months. Data were analysed by non parametric statistics. RESULTS: At the end of the study, 115 teeth (59 group A and 56 group B) were examined. The quality of sealing was evaluated and some differences were reported comparing different types of teeth. The radiographic outcome was evaluated and 94.9% showed to be completely healed in group A and 48.2% in group B (p=0.0001). CONCLUSION: The technique based on NiTi engine driven files and Thermafil heated gutta-percha has shown, after 24 months, results which were comparable to other root canal shaping and filling methods.

The translesion DNA polymerase zeta plays a major role in Ig and bcl-6 somatic hypermutation.

Ig somatic mutations would be introduced by a polymerase (pol) while repairing DNA outside main DNA replication. We show that human B cells constitutively express the translesion pol zeta, which effectively extends DNA past mismatched bases (mispair extender), and pol eta, which bypasses DNA lesions in an error-free fashion. Upon B cell receptor (BCR) engagement and coculture with activated CD4+ T cells, these lymphocytes upregulated pol zeta, downregulated pol eta, and mutated the Ig and bcl-6 genes. Inhibition of the pol zeta REV3 catalytic subunit by specific phosphorothioate-modified oligonucleotides impaired Ig and bcl-6 hypermutation and UV damage-induced DNA mutagenesis, without affecting cell cycle or viability. Thus, pol zeta plays a critical role in Ig and bcl-6 hypermutation, perhaps facilitated by the downregulation of pol eta.

Dysregulation of CD30+ T cells by leukemia impairs isotype switching in normal B cells.

Chronic lymphocytic leukemia (CLL) is associated with impaired immunoglobulin (Ig) class-switching from IgM to IgG and IgA, a defect that leads to recurrent infections. When activated in the presence of leukemic CLL B cells, T cells rapidly up-regulate CD30 through an OX40 ligand and interleukin 4 (IL-4)-dependent mechanism. These leukemia-induced CD30+ T cells inhibit CD40 ligand (CD40L)-mediated S mu-->S gamma and S mu-->S alpha class-switch DNA recombination (CSR) by engaging CD30 ligand (CD30L), a molecule that interferes with the assembly of the CD40-tumor necrosis factor receptor-associated factor (TRAF) complex in nonmalignant IgD+ B cells. In addition, engagement of T cell CD30 by CD30L on neoplastic CLL B cells down-regulates the CD3-induced expression of CD40L. These findings indicate that, in CLL, abnormal CD30-CD30L interaction impairs IgG and IgA production by interfering with the CD40-mediated differentiation of nonmalignant B cells.