Referral Patterns in Oral Medicine: A Retrospective Analysis of an Oral Medicine University Center in Southern Italy

Referral of a patient from one healthcare provider to another is an important part of the medical practice. The aim of this study was to analyze the referral process to the Oral Medicine Unit in a university-based tertiary center in Southern Italy. A chart review of new referrals to the Oral Medicine Unit during a 24-month period was conducted. The following data were recorded: demographic characteristics, medical history, number of physicians seen prior to Oral Medicine assessment, referral source, diagnostic procedures ordered by referrals, reason for referral, site of lesion/condition, final diagnosis. Then, the rates of correct identification for health-care professionals and the appropriateness of the reference diagnosis based on the disease were calculated with descriptive statistic indicators. There were 583 new first consultations. A total of 62.9% of patients were referred by general dental practitioners, 27.4% by physicians, and 9.7% did not have a referral. The most common diseases for referral were immune-mediated diseases (39.6%) and oro-facial pain disorders (25.2%). Only 28.5% of patients had a correct provisional diagnosis. The results of this study show the need to implement curricula in the field of oral medicine among dentistry and medical students, and to support the continuing education among healthcare providers to reduce diagnostic delay for oral diseases

High Fat Diet and Inflammation - Modulation of Haptoglobin Level in Rat Brain

Obesity and dietary fats are well known risk factors for neurodegenerative diseases. The analysis of specific markers, whose brain level can be affected by diet, might contribute to unveil the intersection between inflammation/obesity and neurodegeneration. Haptoglobin (Hpt) is an acute phase protein, which acts as antioxidant by binding free haemoglobin (Hb), thus neutralizing its pro-oxidative action. We previously demonstrated that Hpt plays critical functions in brain, modulating cholesterol trafficking in neurons, beta-amyloid (Aβ) uptake by astrocyte, and limiting Aβ toxicity on these cells. A major aim of this study was to evaluate whether a long term (12 or 24 weeks) high-fat diet (HFD) influences Hpt and Hb expression in rat hippocampus. We also assessed the development of obesity-induced inflammation by measuring hippocampal TNF-alpha, and the extent of protein oxidation by titrating nitro-tyrosine (N-Tyr). Hpt concentration was lower in hippocampus of HFD rats than in control animals, HFD was also associated in hippocampus with the increase of Hb level, inflammation and protein oxidative modification, as evidenced by the increase in the concentration of TNF-alpha and nitro-tyrosine. In fact, TNF-alpha concentration was higher in rats receiving HFD for 12 or 24 weeks compared to controls. N-Tyr concentration was more elevated in hippocampus of HFD than in control rats in both 12 weeks and 24 weeks groups. Finally, we found that the treatment of the human glial cells with cholesterol and fatty acids significantly impairs Hpt secretion in the extracellular compartment. We hypothesize that the HFD-dependent decrease of Hpt in hippocampus, as associated with Hb increase, might enhance the oxidative stress induced by free Hb. Altogether our data, identifying Hpt as a molecule modulated in the brain by dietary fats, may represent one of the first steps in the comprehension of the molecular mechanisms underlying the diet-related effects in the nervous system

Long-term exposure of pancreatic β-cells to palmitate results in SREBP-1C-dependent decreases in GLP-1 receptor signaling via CREB and AKT and insulin secretory response

The effects of prolonged exposure of pancreatic β-cells to high saturated fatty acids on glucagonlike peptide-1 (GLP-1) action were investigated. Murine islets, human pancreatic 1.1B4 cells, and rat INS-1E cells were exposed to palmitate for 24 hours. mRNA and protein expression/phosphorylation were measured by real-time RT-PCR and immunoblotting, respectively. Specific short interfering RNAs were used to knockdown expression of the GLP-1 receptor (Glp1r) and Srebf1. Insulin release was assessed with a specific ELISA. Exposure of murine islets, as well as of human and INS-1E β-cells, to palmitate reduced the ability of exendin-4 to augment insulin mRNA levels, protein content, and release. In addition, palmitate blocked exendin-4-stimulated cAMP-response element-binding protein and v-akt murine thymoma viral oncogene homolog phosphorylation, whereas phosphorylation of MAPK-ERK kinase-1/2 and ERK-1/2 was not altered. Similarly, RNA interference-mediated suppression of Glp1r expression prevented exendin-4-induced cAMP-response element-binding protein and v-akt murine thymoma viral oncogene homolog phosphorylation, but did not impair exendin-4 stimulation of MAPK-ERK kinase-1/2 and ERK-1/2. Both islets from mice fed a high fat diet and human and INS-1E β-cells exposed to palmitate showed reduced GLP-1 receptor and pancreatic duodenal homeobox-1 (PDX-1) and increased sterol regulatory element-binding protein (SREBP-1C) mRNA and protein levels. Furthermore, suppression of SREBP-1C protein expression prevented the reduction of PDX-1 and GLP-1 receptor levels and restored exendin-4 signaling and action. Finally, treatment of INS-1E cells with metformin for 24 h resulted in inhibition of SREBP-1C expression, increased PDX-1 and GLP-1 receptor levels, consequently, enhancement of exendin-4-induced insulin release. Palmitate impairs exendin-4 effects on β-cells by reducing PDX-1 and GLP-1 receptor expression and signaling inaSREBP-1C-dependent manner. Metformin counteracts the impairment of GLP-1 receptor signaling induced by palmitate

Transcriptional regulation of the Ciona Gsx gene in the neural plate

Work by R. E. in the laboratory of H. Y. was supported by a European Molecular Biology Organisation (EMBO) short term fellowship (ASTF 534–2014). Work by P. L. and E. F. was supported by CNRS and the Agence Nationale de la Recherche (ANR-13-BSV2–0011-01,TED; ANR-08-BLAN-0067, Chor-Evo-Net). Work by R. E., A. P. and L. S. in the laboratory of A. S. was supported by SZN PhD fellowships. The group of D. E. K. F. is supported by the Leverhulme Trust (RPG-2016-351). Isolation of the Gsx containing cosmid was conducted in the laboratory of Peter Holland and supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (no. G09218).The ascidian neural plate consists of a defined number of identifiable cells organized in a grid of rows and columns, representing a useful model to investigate the molecular mechanisms controlling neural patterning in chordates. Distinct anterior brain lineages are specified via unique combinatorial inputs of signalling pathways with Nodal and Delta-Notch signals patterning along the medial-lateral axis and FGF/MEK/ERK signals patterning along the anterior-posterior axis of the neural plate. The Ciona Gsx gene is specifically expressed in the a9.33 cells in the row III/column 2 position of anterior brain lineages, characterised by a combinatorial input of Nodal-OFF, Notch-ON and FGF-ON. Here, we identify the minimal cis-regulatory element (CRE) of 376 bp, which can recapitulate the early activation of Gsx. We show that this minimal CRE responds in the same way as the endogenous Gsx gene to manipulation of FGF- and Notch-signalling pathways and to overexpression of Snail, a mediator of Nodal signals, and Six3/6, which is required to demarcate the anterior boundary of Gsx expression at the late neurula stage. We reveal that sequences proximal to the transcription start site include a temporal regulatory element required for the precise transcriptional onset of gene expression. We conclude that sufficient spatial and temporal information for Gsx expression is integrated in 376 bp of non-coding cis-regulatory sequences.PostprintPeer reviewe

Exome-Wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated With Fatty Liver Disease

BACKGROUND & AIMS: Fatty liver disease (FLD) is a growing epidemic that is expected to be the leading cause of end-stage liver disease within the next decade. Both environmental and genetic factors contribute to the susceptibility of FLD. Several genetic variants contributing to FLD have been identified in exome-wide association studies. However, there is still a missing hereditability indicating that other genetic variants are yet to be discovered. METHODS: To find genes involved in FLD, we first examined the association of missense and nonsense variants with alanine amino transferase at an exome-wide level in 425,671 participants from the UK Biobank. We then validated genetic variants with liver fat content in 8930 participants in whom liver fat measurement was available, and replicated 2 genetic variants in 3 independent cohorts comprising 2621 individuals with available liver biopsy. RESULTS: We identified 190 genetic variants independently associated with alanine aminotransferase after correcting for multiple testing with Bonferroni method. The majority of these variants were not previously associated with this trait. Among those associated, there was a striking enrichment of genetic variants influencing lipid metabolism. We identified the variants rs2792751 in GPAM/GPAT1, the gene encoding glycerol-3phosphate acyltransferase, mitochondrial, and rs429358 in APOE, the gene encoding apolipoprotein E, as robustly associated with liver fat content and liver disease after adjusting for multiple testing. Both genes affect lipid metabolism in the liver. CONCLUSIONS: We identified 2 novel genetic variants in GPAM and APOE that are robustly associated with steatosis and liver damage. These findings may help to better elucidate the genetic susceptibility to FLD onset and progression.Peer reviewe

New Insights into the Evolution of Metazoan Tyrosinase Gene Family

Tyrosinases, widely distributed among animals, plants and fungi, are involved in the biosynthesis of melanin, a pigment that has been exploited, in the course of evolution, to serve different functions. We conducted a deep evolutionary analysis of tyrosinase family amongst metazoa, thanks to the availability of new sequenced genomes, assessing that tyrosinases (tyr) represent a distinctive feature of all the organisms included in our study and, interestingly, they show an independent expansion in most of the analyzed phyla. Tyrosinase-related proteins (tyrp), which derive from tyr but show distinct key residues in the catalytic domain, constitute an invention of chordate lineage. In addition we here reported a detailed study of the expression territories of the ascidian Ciona intestinalis tyr and tyrps. Furthermore, we put efforts in the identification of the regulatory sequences responsible for their expression in pigment cell lineage. Collectively, the results reported here enlarge our knowledge about the tyrosinase gene family as valuable resource for understanding the genetic components involved in pigment cells evolution and development

Ciona intestinalis as a Marine Model System to Study Some Key Developmental Genes Targeted by the Diatom-Derived Aldehyde Decadienal

The anti-proliferative effects of diatoms, described for the first time in copepods, have also been demonstrated in benthic invertebrates such as polychaetes, sea urchins and tunicates. In these organisms PUAs (polyunsaturated aldehydes) induce the disruption of gametogenesis, gamete functionality, fertilization, embryonic mitosis, and larval fitness and competence. These inhibitory effects are due to the PUAs, produced by diatoms in response to physical damage as occurs during copepod grazing. The cell targets of these compounds remain largely unknown. Here we identify some of the genes targeted by the diatom PUA 2-trans-4-trans-decadienal (DD) using the tunicate Ciona intestinalis. The tools, techniques and genomic resources available for Ciona, as well as the suitability of Ciona embryos for medium-to high-throughput strategies, are key to their employment as model organisms in different fields, including the investigation of toxic agents that could interfere with developmental processes. We demonstrate that DD can induce developmental aberrations in Ciona larvae in a dose-dependent manner. Moreover, through a preliminary analysis, DD is shown to affect the expression level of genes involved in stress response and developmental processes

Patterning of brain precursors in ascidian embryos

International audienceIn terms of their embryonic origins, the anterior and posterior parts of the ascidian central nervous system (CNS) are associated with distinct germ layers. The anterior part of the sensory vesicle, or brain, originates from ectoderm lineages following a neuro-epidermal binary fate decision. In contrast, a large part of the remaining posterior CNS is generated following neuro-mesodermal binary fate decisions. Here, we address the mechanisms that pattern the anterior brain precursors along the medial-lateral axis (future dorsal-ventral) at neural plate stages. Our functional studies show that Nodal signals are required for induction of lateral genes including Delta-like, Snail, Msxb and Trp. Delta-like/Notch signalling induces intermediate (Gsx) over medial (Meis) gene expression in intermediate cells, while the combinatorial action of Snail and Msxb prevents the expression of Gsx in lateral cells. We conclude that despite the distinct embryonic lineage origins within the larval CNS, the mechanisms that pattern neural precursors are remarkably similar

Approccio analitico integrato per la caratterizzazione di suoli inquinati da metalli pesanti

L’indagine del suolo e delle forme di inquinamento in esso presenti, fino a livelli micrometrici, è uno strumento essenziale ai fini della comprensione delle cause di inquinamento e della definizione e realizzazione delle strategie di bonifica. In presenza di inquinamento da metalli pesanti (MP), non è sufficiente individuare gli elementi con concentrazioni superiori ai valori soglia di contaminazione stabiliti dalla legge, ma occorre altresì indagare la speciazione dei MP e la loro biodisponibilità. In questo studio, tecniche analitiche innovative che impiegano raggi-X e procedure convenzionali sono state utilizzate per caratterizzare alcuni suoli prelevati a Taranto e Altamura (BA), in siti contaminati da MP. Durante il campionamento, sono state individuate le zone a maggiore concentrazione di MP mediante fluorescenza portatile di raggi-X. I campioni sono stati sottoposti alle principali analisi chimico-fisiche, inclusa l’estrazione con DTPA. Il contenuto totale di MP è stato determinato con ICP-AES, dopo digestione acida in microonde. La distribuzione di MP nelle fasi solide del suolo è stata indagata mediante estrazioni sequenziali (metodo BCR modificato, 4 step), nonché analisi di microfluorescenza di raggi-X (μ-XRF) su sezioni sottili di suolo. Un’aliquota finemente macinata di ciascun campione è stata analizzata mediante diffrazione di raggi-X quantitativa e fluorescenza di raggi-X a dispersione di lunghezza d’onda. I due suoli di Taranto, simili tra loro per le proprietà fisico-chimiche (franco sabbiosi, calcarei, pH=8, Corg 2,8%) e mineralogiche, sono risultati caratterizzati da un contenuto elevato di Cu (229 e 140 mg/kg), Pb (415 e 292 mg/kg) e Zn (636 e 574 mg/kg). La frazione estratta in DTPA non ha superato il 12% (Cu), 17% (Pb) e 5% (Zn) rispetto al totale. Le estrazioni sequenziali hanno rivelato che oltre il 92% di questi MP è associato alle frazioni recalcitranti del suolo. In media, il 76% (Cu), 60% (Pb) e 77% (Zn) sono stati determinati nella frazione residua, e il 22% (Cu), 36% (Pb) e 16% (Zn) al termine del IV step (frazione potenzialmente legata alla sostanza organica e ai solfuri). Le mappe μ-XRF hanno rivelato una distribuzione eterogenea di Cu, Pb e Zn, con spot ad elevata concentrazione di dimensioni variabili. I tre MP sono risultati spesso associati tra loro, facendo ipotizzare la presenza di leghe metalliche (stagno al Pb) riconducibili ad attività militari pregresse svolte nel sito. Tali risultati, unitamente ai dati ecotossicologici che hanno rivelato l’assenza di fitotossicità dei suoli, dimostrano la limitata mobilità e disponibilità dei tre MP. Tuttavia, i livelli di Pb misurati nell’estratto di DTPA superano i valori mediamente riscontrati in suoli prossimi a reti stradali, indicando un potenziale rischio ambientale per questo elemento. I dati relativi al sito di Altamura sono in fase di acquisizione. ACKNOWLEDGEMENTS La ricerca è stata finanziata dal Programma “Future in research” (UE, Regione Puglia, A.R.T.I.)