Is There a Correlation between Gingival Display and Incisal Inclination in a Gummy Smile? Study on Cephalometric Parameters

Background: Excessive gingival display or “gummy smile” is a clinical condition where a maxillary gum shows between the inferior line of the superior lip and the gingival line of the incisive superior during a spontaneous smile. The aim of this research was to understand the various skeletal and dentoalveolar components contributing to a gummy smile in a sample of 120 patients. Material and Methods: This retrospective case-control study had the primary objectives of analyzing the existence of a correlation between the presence of gingival exposure and the alteration of the inclination of the upper incisors with respect to the Frankfurt plane, the Palatine plane (bi-spinal) and to the NA line in a sample of orthodontic patients, and also evaluating the association with skeletal, dental, and aesthetic cephalometric parameters. Result and Conclusions: In our study, it’s emerged a correlation between the gingival exposure and the presence of alterations to incisal torque in the vestibular direction and the quantity of maxillary gingiva evident during the smile, which is correlated in particular to the Is–Sts distance, overjet and overbite. The major indicative data, therefore, are related to the vertical position of the upper incisors, in particular with respect to the upper lip and to the sagittal position

Integrating Terminological Tools and Semantic Archaeological Information: the ICCD RA Schema and Thesaurus.

This paper describes the process of mapping, translation and publication in SKOS format of the RA Thesaurus, a terminological tool developed by the Italian Ministry of Cultural Heritage (MiBACT) as a part of the official documentation used for the recording of archaeological finds. In particular, the RA Thesaurus is intended to provide unified and meaningful terminology for the description of archaeological objects according to the MiBACT official cataloguing standards. After describing the thesaurus, the logic with which it was developed and its internal structure, we report the various phases of the conversion, both from a theoretical and implementation point of view, and the various technologies used for the publication of the thesaurus on the web. This work is a collaborative effort between PIN and MiBACT carried out under the ARIADNE project

Description, Nomenclature, and Mapping of a Novel Cerebello-Renal Syndrome with the Molar Tooth Malformation

Cerebello-oculo-renal syndromes (CORSs) and Joubert syndrome (JS) are clinically and genetically heterogeneous autosomal recessive syndromes that share a complex neuroradiological malformation resembling a molar tooth on brain axial images, a condition referred to as “molar tooth on imaging” (MTI) or the “molar tooth sign.” The current literature on these syndromes is complex, with overlapping and incomplete phenotypes that complicate the selection of clinically homogeneous cases for genetic purposes. So far, only one locus (JBTS1 on 9q34) has been mapped, in two families with JS. Here, we describe a large consanguineous family with JS and nephronophthisis, representing a novel cerebello-renal phenotype. We have mapped this condition to the pericentromeric region of chromosome 11 and have named the locus “CORS2.” The acronym “CORS” is proposed for all loci associated with JS, CORSs, and related phenotypes sharing the MTI, because this neuroradiological sign seems to be the unifying feature of these clinically heterogeneous syndromes

A Rapid and Cheap Method for Extracting and Quantifying Lycopene Content in Tomato Sauces: Effects of Lycopene Micellar Delivery on Human Osteoblast-Like Cells

Identifying and quantifying the beneficial molecules contained in nutraceuticals is essential to predict the effects derived from their consumption. This study explores a cheap and rapid method for quantifying lycopene content from a semi-solid matrix. In addition, it compares the in vitro effects of the extracts obtained from different tomato sauces available on the local market with Osteocol®, a patented tomato sauce from southern Italy. We performed a liquid extraction of lycopene using suitable solvents. The lycopene extracted was encapsulated in surfactant micelles and finally tested in vitro on Saos-2 cells. The effects exerted by lycopene on ALP and Wnt/β-catenin pathways were investigated by Western blotting. Hexane was found to be the best solvent for lycopene extraction. Spectrophotometrical and HPLC analyses showed similar trends. Osteocol® contained 39 ± 4 mg lycopene per 100 g of sauce, while the best commercial product contained 19 ± 1 mg/100 g. The Osteocol® lycopene extract increased ALP and β-catenin protein expressions in a dose-dependent manner, also showing statistically significant results (p ® represents a useful supplement in the prevention of osteoporosis compared to its commercial competitors

Haploidentical HSCT for hemoglobinopathies: improved outcomes with TCRαβ+/CD19+-depleted grafts

We examined outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) using T-cell receptor alpha beta(+) (TCR alpha beta(+))/CD19(+)-depleted grafts (TCR group, 14 patients) in children with hemoglobinopathies. Patients received a preparative regimen consisting of busulfan, thiotepa, cyclophosphamide, and antithymocyte globulin preceded by fludarabine, hydroxyurea, and azathioprine. The median follow-up among surviving patients was 3.9 years. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 84% and 69%, respectively. The incidence of graft failure was 14%. We compared outcomes to a historical group of 40 patients with hemoglobinopathies who received CD34(+)-selected grafts (CD34 group). The median follow-up of surviving patients for the CD34 group was 7.5 years. The 5-year probabilities of OS and DFS were 78% and 39%, respectively. The CD34 group had a significantly higher incidence of graft failure (45%) than the TCR group (14%) (P = .048). The incidences of grades 2 to 4 acute graft-versus-host disease (GVHD) in the TCR and CD34 groups were 28% and 29%, respectively, and 21% and 10% (P = .1), respectively, for extensive chronic GVHD. Viral reactivation was common in both groups. The overall incidence of posttransplant lymphoproliferative disorders for the entire group was 16%. Among all patients, 5 developed autoimmune hemolytic anemia or thrombocytopenia, with the overall cumulative incidence of 11%. The 2 groups showed suboptimal CD4(+) recovery within the first 6 months of transplantation with no significant difference between groups. These data demonstrate that TCR alpha beta(+)/CD19(+)-depleted grafts are associated with a reduced incidence of graft failure, but delayed immune reconstitution and associated morbidity and mortality remain a significant challenge

HLA-Cw6 and other HLA-C alleles, as well as MICB-DT, DDX58 and TYK2 genetic variants associate with optimal response to anti-IL-17A treatment in patients with psoriasis

Our pharmacogenomic study evaluated the influence of the presence/absence of genetic variants of psoriasis-risk loci on the clinical response to secukinumab. Differences in the single-nucleotide polymorphism (SNP) pattern characterizing HLA-Cw6+ or HLA-Cw6- patient subpopulations, showing high or low responses to secukinumab, were also analysed

Preventing muscle wasting: pro‐insulin C‐peptide prevents loss in muscle mass in streptozotocin‐diabetic rats

Abstract Background C‐peptide therapy exerts several positive actions on nerves, vasculature, smooth muscle relaxation, kidney function and bone. To date, the role of C‐peptide in preventing type 1 diabetes‐related muscle atrophy has not been investigated. Our aim was to evaluate if C‐peptide infusion prevents muscle wasting in diabetic rats. Methods Twenty‐three male Wistar rats were randomly divided into three groups: normal control group, diabetic group and diabetic group plus C‐peptide. Diabetes was induced by streptozotocin injection, and C‐peptide was administered subcutaneously for 6 weeks. The blood samples were obtained at baseline, before streptozotocin injection and at the end of the study to assess C‐peptide, ubiquitin and other laboratory parameters. We also tested the ability of C‐peptide to regulate the skeletal muscle mass, the ubiquitin–proteasome system, the autophagy pathway as well as to improve muscle quality. Results C‐peptide administration reversed hyperglycaemia (P = 0.02) and hypertriglyceridaemia (P = 0.01) in diabetic plus C‐peptide rats compared with diabetic control rats. The diabetic‐control animals displayed a lower weight of the muscles in the lower limb considered individually than the control rats and the diabetic plus C‐peptide rats (P = 0.03; P = 0.03; P = 0.04; P = 0.004, respectively). The diabetic‐control rats presented a significantly higher serum concentration of ubiquitin compared with the diabetic plus C‐peptide and the control animals (P = 0.02 and P = 0.01). In muscles of the lower limb, the pAmpk expression was higher in the diabetic plus C‐peptide than the diabetic‐control rats (in the gastrocnemius, P = 0.002; in the tibialis anterior P = 0.005). The protein expression of Atrogin‐1 in gastrocnemius and tibialis was lower in the diabetic plus C‐peptide than in diabetic‐control rats (P = 0.02, P = 0.03). After 42 days, the cross‐sectional area in the gastrocnemius of the diabetic plus C‐peptide group had been reduced by 6.6% while the diabetic‐control rats had a 39.5% reduction compared with the control animals (P = 0.02). The cross‐sectional area of the tibialis and the extensor digitorum longus muscles was reduced, in the diabetic plus C‐peptide rats, by 10% and 11%, respectively, while the diabetic‐control group had a reduction of 65% and 45% compared with the control animals (both P < 0.0001). Similar results were obtained for the minimum Feret's diameter and perimeter. Conclusions C‐peptide administration in rats could protect skeletal muscle mass from atrophy induced by type 1 diabetes mellitus. Our findings could suggest that targeting the ubiquitin–proteasome system, Ampk and muscle‐specific E3 ubiquitin ligases such as Atrogin‐1 and Traf6 may be an effective strategy for molecular and clinical intervention in the muscle wasting pathological process in T1DM

HLA-Cw6 and other HLA-C alleles, as well as MICBDT, DDX58, and TYK2 genetic variants associate with optimal response to anti-IL-17A treatment in patients with psoriasis

Objective: Our pharmacogenomic study evaluated the influence of the presence/absence of genetic variants of psoriasis-risk loci on the clinical response to secukinumab. Differences in the single-nucleotide polymorphism (SNP) pattern characterizing HLA-Cw6+ or HLA-Cw6 12 patient subpopulations, showing high or low responses to secukinumab, were also analyzed. Methods: 417 SNPs were analyzed by Next-Generation Sequencing technology, in a cohort of 62 psoriatic patients and undergone secukinumab treatment. Univariate regression analysis was employed to examine the association between SNP and clinical response to secukinumab. Multivariate analysis was also performed to assess multivariate differences in SNP pattern of HLA-Cw6+ or HLA-Cw6 12 patients showing high or low responses to secukinumab. Results: Eight SNPs in HLA-C and upstream region (rs13207315, rs6900444, rs12189871, rs12191877, rs4406273, and rs10484554), including HLA-Cw6 classical allele (rs1131118), and three in MICB-DT (rs9267325), DDX58 (rs34085293) and TYK2 (rs2304255) genes, associating with excellent response to secukinumab were identified. Importantly, rs34085293 or rs2304255 SNP status defined a subgroup of super-responder patients. We also found that HLA-Cw6+ and HLA-Cw6 12 patients carried out specific patterns of SNPs associating with different responses to secukinumab. Conclusion: Assessment of HLA-Cw6, together with other allelic variants of genes, could be helpful to define patients which better benefit from anti-IL-17 therapy. Abbreviations: PASI: Psoriasis Area and Severity Index; SNP: Single-Nucleotide Polymorphism Rs: Reference SNP; PASI75: 75% reduction in Psoriasis Area and Severity Index; PASI90: 90% reduction in Psoriasis Area and Severity Index; PASI100: 100% reduction in Psoriasis Area and Severity Index; NGS: Next-Generation Sequencing; OR: Odds Ratio; CAP: Canonical Analysis of Principal coordinates; BMI: Body Mass Index; LD: Linkage Disequilibriu

Genome-Wide DNA Methylation Profiling Solves Uncertainty in Classifying NSD1 Variants

Background: Inactivating NSD1 mutations causing Sotos syndrome have been previously associated with a specific genome-wide DNA methylation (DNAm) pattern. Sotos syndrome is characterized by phenotypic overlap with other overgrowth syndromes, and a definite diagnosis might not be easily reached due to the high prevalence of variants of unknown significance (VoUS) that are identified in patients with a suggestive phenotype. Objective: we performed microarray DNAm profiling in a set of 11 individuals with a clinical suspicion of Sotos syndrome and carrying an NSD1 VoUS or previously unreported variants to solve uncertainty in defining pathogenicity of the observed variants. The impact of the training cohort size on sensitivity and prediction confidence of the classifier was assessed. Results: The Sotos syndrome-specific DNAm signature was validated in six individuals with a clinical diagnosis of Sotos syndrome and carrying bona fide pathogenic NSD1 variants. Applying this approach to the remaining 11 individuals with NSD1 variants, we succeeded in confirming pathogenicity in eight subjects and excluding the diagnosis of Sotos syndrome in three. The sensitivity and prediction confidence of the classifier based on the different sizes of the training sets did not show substantial differences, though the overall performance was improved by using a data balancing strategy. Conclusions: The present approach solved uncertainty in cases with NDS1 VoUS, further demonstrating the clinical utility of DNAm profiling