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Hereditary gingival fibromatosis (HGF) is a rare oral condition that may appear as an isolated entity or as part of a genetic disease or syndrome. Molecular and biochemical mechanisms that trigger this pathologic process are not completely understood. In this article, we present a rare case of hereditary gingival fibromatosis in conjunction with a syndromic phenotype, associated with a rare missense mutation of the KCNK4 gene. This mutation induces a change in the structure of the TRAAK channel belonging to the 2-pore potassium channels. The gain of function promoted by the mutation could represent the pathogenetic basis of gingival fibromatosis.

To explore the prevalence of temporomandibular disorders (TMD) in patients affected by multiple sclerosis (MS) and whether there is a correlation between TMD prevalence and MS severity.PubMed, Web of Science, and Lilacs were systematically searched until July 30 2022, to identify studies presenting patients affected by MS and whether there is a correlation between TMD prevalence and MS severity.Out of 292 papers, 8 studies were included with 1312 study participants. Among the 8 studies, 5 had a control group; 5 used the RDC/TMD criteria, 1 used the NOT-S instrument, and 2 did not define a standardized method to define TMD symptoms. Meta-analysis revealed that the MS group had a higher rate than the control group, showing an association between MS and TMD (RR 2.10; 95% CI: 1.21-3.65).These findings show an association between TMD and MS.Australian Longitudinal Study of MS (AMSLS); Computed Tomography (CT); Community Periodontal Index of Treatment Needs (CPITN); Central Nervous System (CNS); Decayed, Missing, and Filled (DMF); Decayed, Missing, or Filled Teeth Index (DMFT); Expanded Disability Status Scale (EDSS); European Academy of Craniomandibular Disorders (EACD); Healthy Controls (HC); International Prospective Register of Systematic Reviews (PROSPERO); Multiple Sclerosis (MS); Nordic Orofacial Test-Screening (NOT-S); Participants, model of Intervention, Comparison and Outcome (PICO); Preferred Reporting Items for Systematic Reviews (PRISMA); Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD); Temporomandibular Joint (TMJ); Temporomandibular Disorders (TMD); World Health Organization (WHO).

Simple Summary Prognostic models to choose the right treatment schedule are needed in order to translate into practice a personalized approach. None of these models have been still entered into the clinical practice for what concern oral squamous cell carcinoma (OSCC). In this manuscript we performed a systematic review and subsequent quality assessment of already development prognostic model for OSCC with the aim to take stock of the situation on their possible clinical use. Abstract (1) Background: An accurate prediction of cancer survival is very important for counseling, treatment planning, follow-up, and postoperative risk assessment in patients with Oral Squamous Cell Carcinoma (OSCC). There has been an increased interest in the development of clinical prognostic models and nomograms which are their graphic representation. The study aimed to revise the prognostic performance of clinical-pathological prognostic models with internal validation for OSCC. (2) Methods: This systematic review was performed according to the Cochrane Handbook for Diagnostic Test Accuracy Reviews chapter on searching, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, and the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). (3) Results: Six studies evaluating overall survival in patients with OSCC were identified. All studies performed internal validation, while only four models were externally validated. (4) Conclusions: Based on the results of this systematic review, it is possible to state that it is necessary to carry out internal validation and shrinkage to correct overfitting and provide an adequate performance for optimism. Moreover, calibration, discrimination and nonlinearity of continuous predictors should always be examined. To reduce the risk of bias the study design used should be prospective and imputation techniques should always be applied to handle missing data. In addition, the complete equation of the prognostic model must be reported to allow updating, external validation in a new context and the subsequent evaluation of the impact on health outcomes and on the cost-effectiveness of care.

Inflammation seems to play a critical role in the development and progression of different cancers. Neutrophil-to-lymphocyte ratio (NLR) is an easily measurable marker of systemic inflammation. The purpose of this systematic review and meta-analysis was to evaluate the prognostic role of the pre-treatment neutrophil-to-lymphocyte ratio (NLR), in terms of overall survival (OS) and disease-free survival (DFS), in patients with primary head and neck squamous cell carcinoma (HNSCC) treated by surgery alone or followed by chemo/radiotherapy. This systematic review was performed according to the guidelines reported in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Meta-analysis of overall survival and disease-free survival was performed using the inverse of variance test. Fixed-effect models were used on the basis of the presence of heterogeneity. Risk of bias assessment and trial sequential analysis (TSA) were also performed; the quality of the evidence was evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The analysis revealed that a higher value of pre-treatment NLR correlates with a statistically significant decrease of overall survival (HR, 1.56; 95% CI: [1.35, 1.80]; P

Background The occurrence of a head and neck tumoral mass at birth or shortly afterwards may cause concern and the differential diagnosis may be complex. Sialoblastoma is a rare epithelial tumor of the salivary glands of uncertain malignant potential, which typically affects children and arises more frequently in the parotid gland. The diagnosis may be challenging, as the differential diagnosis is wide. Methods The present paper reports a case of sialoblastoma, present at birth, diagnosed in a 20-day-old girl. The patient was submitted to surgery and the neoplasm was excised "en bloc". We also carried out a thorough review of all cases of sialoblastoma, diagnosed in the first year of life and reported in the literature, using the PubMed database. Results A final diagnosis of sialoblastoma was rendered through histological examination and immunohistochemistry. The neoplasm resulted entirely excised with disease-free surgical margins, and no other therapy was necessary. The 2 years clinical and instrumental follow-up was uneventful. Conclusions Through the present case and the review of the literature, the state of the art is established with regard the clinical aspects, the morphological and immunophenotypic features for diagnostic purpose. Moreover, parameters that can influence the prognosis are evaluated, paying attention especially to the cases of sialoblastoma diagnosed in the first year of life.

Ectopic lower third molar is an uncommon condition, and its etiology remains unclear. The main approach used for its surgical removal is the intraoral one, but there are cases in which this may not be the best option. When the lower third molar is located below the lower alveolar canal or when it is close to the lower edge of the jaw, the most recommended approach is the extraoral one. The critical issues related to the extraoral approach are the possibility of damaging anatomical structures such as marginal mandibular branch of the facial nerve (craniofacial nerve VII), facial artery and vein, and submental artery. This complication can occur during incision and dissection of the superficial layers or during osteotomy with rotating instruments.This paper reports a case of extraction of ectopic lower third molar using a minimally invasive extraoral approach combined with piezoelectric surgery in order to prevent intraoperative injury of anatomical structures.

BACKGROUND Primary salivary gland lymphomas are unusual, accounting for 2.5% to 4.5% of salivary gland tumours. More than 90% are non-Hodgkin lymphomas (NHLs) and extranodal marginal zone lymphoma (EMZL) is the most common histotype. METHODS A patient with a history of CD5-negative and CD23-negative clonal B-cell lymphocytosis presented a nodule in the deeper left parotid region, discovered accidentally during a follow-up for the lymphocytosis. Ultrasounds and Magnetic resonance imaging showed multiple nodules, the biggest of about 1.5 centimetres, partly solid and partly cystic. US-guided fine needle aspiration cytology and flow cytometry were executed. Final diagnosis of a monoclonal B-cell lymphoproliferative disorder was rendered, and the patient underwent to partial left parotidectomy. RESULTS Histological examination and immunohistochemistry allowed to formulate the final diagnosis of an extranodal non-Hodgkin B-cell marginal zone lymphoma (MZL) occurring in the context of a lympho-epithelial cyst was rendered. The 2 years clinical and instrumental follow-up was uneventful. CONCLUSIONS The diagnostic evaluation of a LEC has to include the possibility of a concurrent EMZL, mainly in case of high risk biological and clinical conditions like CBL.

The aim of this trial was to study the concentration of zinc (Zn), iron (Fe), copper (Cu), manganese (Mn), selenium (Se), cobalt (Co) and iodine (I) in milk and blood serum of lactating donkeys, taking into account the effects of lactation stage and dietary supplementation with trace elements. During a 3-month period, 16 clinically healthy lactating donkeys (Martina-Franca-derived population), randomly divided into two homogeneous groups (control (CTL) and trace elements (TE)), were used to provide milk and blood samples at 2-week intervals. Donkeys in both groups had continuous access to meadow hay and were fed 2.5 kg of mixed feed daily, divided into two meals. The mixed feed for the TE group had the same ingredients as the CTL, but was supplemented with a commercial premix providing 163 mg Zn, 185 mg Fe, 36 mg Cu, 216 mg Mn, 0.67 mg Se, 2.78 mg Co and 3.20 mg I/kg mixed feed. The concentrations of Zn, Fe, Cu, Mn, Se, Co and I were measured in feeds, milk and blood serum by inductively coupled plasma-MS. Data were processed by ANOVA for repeated measures. The milk concentrations of all the investigated elements were not significantly affected by the dietary supplementation with TE. Serum concentrations of Zn, Fe, Cu Mn and Se were not affected by dietary treatment, but TE-supplemented donkeys showed significantly higher concentrations of serum Co (1.34 v. 0.69 μg/l) and I (24.42 v. 21.43 μg/l) than unsupplemented donkeys. The effect of lactation stage was significant for all the investigated elements in milk and blood serum, except for serum manganese. A clear negative trend during lactation was observed for milk Cu and Se concentrations (-38%), whereas that of Mn tended to increase. The serum Cu concentration was generally constant and that of Co tended to increase. If compared with data reported in the literature for human milk, donkey milk showed similarities for Zn, Mn, Co and I. Furthermore, this study indicated that, in the current experimental conditions, the mineral profile of donkey milk was not dependent on dietary TE supply.

Sheep develop clinical diseases after 3-5 years after infection with Mycobacterium avium subsp. paratuberculosis (MAP). Clinical symptoms of paratuberculosis include persistent diarrhea and weight loss due to a chronic inflammation of the small intestine. Tissue alterations in the areas of the ileo-cecal junction are often observed. Here, we investigate the molecular processes underlying tissue damages in intestinal mucosa of 14 sheep showing either tuberculoid or lepromatous form of MAP enteritis. We found that E-cadherins, alpha-catenin and beta1-integrins were present at significant low levels in tissues of sheep affected by lepromatous form and that this pattern was associated with high expression of TGF-beta, IL-10, IL-1beta, and TNF-alpha and with a modest increase of CD4+ and CD25+ T cells. Tissues of sheep with the tuberculoid form showed high expression of IFNgamma, IL-12, and MCP-1 and a significant presence of CD4+ and CD25+ T cells. Finally, anti-transglutaminase (tTG) IgG1 antibodies were detected in sera of infected animal belonging to both groups, as already described for human inflammatory bowel diseases. Our results further stress the similarities in the clinical and histological features between ruminant paratuberculosis and human intestinal inflammatory diseases.

Donkey’s milk may be considered a valid alternative, for infant nutrition, to powdered milks, soybean milk or other formulas, since its composition in lipids and proteins is very close to human milk. The aim of the present study is to characterize “donkey’s milk” product, especially with regard to the protein fractions. Three different chromatographic approaches for donkey’s milk proteins separation are described, based on their different isoelectric points, hydrophobicity and molecular mass. The proteins obtained were further separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis and identified by N-terminal sequencing. α S1 - and β-caseins, lysozyme, α-lactalbumin, β-lactoglobulin were identified. Furthermore, the content of α-lactalbumin, β-lactoglobulin, and lysozyme in donkey’s milk was determined by a reversed-phase HPLC method. The β-lactoglobulin and α-lactalbumin content was 3.75 and 1.8 mg/ml, respectively (mean values). The present study showed the nutritional properties of donkey’s milk characterized by low casein and high lysozyme content (1.0 mg/ml) compared with other kinds of milks.

An investigation was made of the role exerted by some residues supposed to be involved in the intersubunit interaction and also in the catalytic site of homotetrameric human cytidine deaminase (T-CDA). Attention was focused on Y33, Y60, R68, and F137 residues that are a part of a conserved region in most T-CDAs. Hence, a series of site-directed mutagenesis experiments was set up obtaining seven mutants: Y60G, Y33G, Y33F Y33S, F137A, R68G, and R68Q. Each active purified mutant protein was characterized kinetically, with a series of substrates and inhibitors, and the effect of temperature on enzyme activity and stability was also investigated. Circular dichroism (CD) experiments at different temperatures and in presence of small amounts of sodium dodecyl sulphate (SDS) were performed in all the soluble mutant CDAs. The results obtained by site-directed mutagenesis studies were compared to the crystallographic data of B. subtilis CDA and E. coli CDA and to molecular modeling studies previously performed on human CDA. The mutation of Y60 to glycine produced an enzyme with a more compact quaternary structure with respect to the wild-type; this mutation did not have a dramatic effect on cytidine deamination, but it slightly affected the binding with the substrate. None of the mutant CDAs in Y33 showed enzymatic activity; they existed only as monomers, indicating that this residue, located at the intersubunit interface, may be responsible for the correct folding of human CDA. The insertion of an alanine instead of phenylalanine at position 137 led to a soluble but completely inactive enzyme unable to form a tetramer, suggesting that F137 residue may be important for the assembling of the tetramer and also for the arrangement of the CDA active site. Finally, R68G and R68Q mutations revealed that the presence of the amino group seems to be important for the catalytic process but not for substrate binding, as already shown in B. subtilis CDA. The quaternary structure of R68Q was not affected by the mutation, as shown by the SDS-induced dissociation experiments and CD studies, whereas R68G dissociated very easily in presence of small amounts of SDS. These experiments indicated that in the human CDA, the side chain of arginine 68 involved in the catalytic process in one subunit active site might come from another subunit. The data obtained from these studies confirmed the presence of a complicated set of intersubunit interactions in the active site of human CDA, as shown in other T-CDAs.

The aim of this trial was to study the concentration of Ti, V, As, Rb, Sr, Mo, Cd, Cs, and Pb in donkey milk and blood serum. One hundred twelve individual milk and blood serum samples were collected from 16 lactating donkeys (Martina-Franca-derived population; 6 to 12 yr old; 3 to 7 parities; average live weight 205.4kg; 32 to 58 d after foaling at the beginning of the trial) during a 3-mo-long experiment. The samples were analyzed for the aforementioned elements by inductively coupled plasma-mass spectrometry. Feedstuff and drinking water were also analyzed for the investigated elements. Data were processed by ANOVA for repeated measures. Average milk concentrations (±SD) of Ti, Rb, Sr, Mo, Cs, and Pb were 77.3 (±7.7), 339.1 (±82.1), 881.7 (±270.4), 4.5 (±1.6), 0.49 (±0.09), and 3.2 (±2.7) μg/L, respectively. More than 80% of samples were below the limit of detection for V, As, and Cd in milk and for Cd, and Pb in blood serum. The lower bound calculated for milk V, As, and Cd was 0.03μg/L for the 3 elements, the upper bound was calculated at 0.23, 0.10, and 0.31μg/L and the maximum value was observed at 0.54, 0.15, and 0.51μg/L, respectively. The average milk concentrations of Ti, Rb, Sr, Mo, and Cs were 600, 458, 346, 16, and 294%, respectively, than those of blood serum. Yet, Cs concentrations were in the same order of magnitude in milk and serum. Moderate to strong positive and significant correlation coefficients were observed between milk and blood serum concentrations for Ti, Rb, Sr, and Cs. The effect of the stage of lactation was significant for all the investigated elements in milk and blood serum, but most of the elements showed only small changes or inconsistent trends, and only the concentrations of Rb and Sr showed decreasing trends both in milk and blood serum. The relationship between milk and blood serum element concentrations indicates that the mammary gland plays a role in determining the milk concentrations of Mo, Ti, Rb, Sr, Mo, and Cs. In the current experimental conditions, in agreement with the low levels in drinking water and feedstuff, donkey milk concentration of potentially toxic elements was very low and did not raise health concerns for human consumption.

In order to design new efficient cytidine based drugs, an intersubunit interactions study related to the active site has been performed on the wild-type cytidine deaminase (CDA) and on the mutant enzyme F137W/W113F. F137 is the homologous to the Bacillus subtilis CDA F125 involved in the subunit interactions. In presence of the dissociating agent SDS, wild-type human CDA dissociate into enzymatically inactive monomers without intermediate forms via a non-cooperative transition. Extensive dialysis or dilution of the inactivated monomers restores completely the activity. The presence of the strong human CDA competitive inhibitor 5-fluorozebularine disfavour dissociation of the tetramer into subunits in the wild-type CDA but not in mutant enzyme F137W/W113F.

Recent clinical studies have demonstrated that feeding with asses milk is a safe and valid treatment for infants affected by protein intolerance to dairy cows milk (Businco et al., 2000; Iacono et al., 1992). In fact, the composition of asses milk is similar to humans milk, especially concerning the lipid and protein fraction contents (Fantuz et al., 2001; Salimei et al., 2004). Furthermore, the protein fraction in asses milk is characterized by low casein and β-lactoglobulin content, probably responsible for the hypoallergenic characteristics of this milk, and by a quite high lysozime content (Fantuz et al., 2001; Salimei et al., 2004). In any case, there is not much information regarding the caseinic fractions of asses milk in the literature. Therefore, in the present study αS1and β-caseins were purified from asses milk by gel filtration chromatography followed by anion exchange chromatography on HPLC. The obtained caseins were characterized by SDS-PAGE and, after blotting on a PVDF membrane, were identified by N-terminal sequencing.

The aim of this trial was to study the content of calcium, phosphorus, potassium, sodium and magnesium in donkey milk. Individual milk samples obtained from 16 lactating jennies during a 3 month experiment were analyzed for Ca, P, K, Na and Mg by inductively coupled plasma-mass spectrometry. Average milk concentrations of Ca, P, K, Na and Mg were 807.09 mg L −1 , 638.42 mg L −1 , 746.61 mg L −1 , 140.94 mg L −1 , 81.69 mg L −1 , respectively. The Ca/P and Na/K ratios averaged 1.26 and 0.19, respectively. The concentration of the studied minerals was affected by the stage of lactation showing a decreasing trend for Ca, P and Mg. The correlation coefficients among all studied minerals were positive and significant except between Ca and Na. Results indicated that generally the concentration of macro elements in donkey milk is lower compared with milk from conventional dairy species and higher than human milk.

Protein fraction characterization of sheep milk from the Comisana breed S. Vincenzetti & P. Polidori & P. Mariani & A. Vita Published online: 7 August 2008 # Springer Science + Business Media B.V. 2008

The thermal stability of human cytidine deaminase (CDA), an enzyme involved in pyrimidine metabolism was investigated. With this in view, the residues R68 and Y60, supposed to be involved in the intersubunit interactions and in the catalytic site of CDA, were mutated to glutamine and glycine, respectively. Thermal stability experiments were performed on the purified mutants by means of circular dichroism and enzymatic assays. The results obtained should be useful for designing more efficient cytidine based drugs for chemotherapy.

In the recent years the interest around donkey’s milk had a marked increase since it has been demonstrated that this milk can be used for feeding of infants affected by dairy cow’s milk protein intolerance (Businco et al., 2000; Iacono et al., 1992).

An intersubunit interactions study related to the active site has been performed on the wild-type cytidine deaminase (CDA) and on the mutant enzyme F137W/W113F. F137 is the homologous to the Bacillus subtilis CDA F125 involved in the subunit interactions. In the presence of SDS, wild-type human CDA dissociates into enzymatically inactive monomers without intermediate forms via a non-cooperative transition. Extensive dialysis or dilution of the inactivated monomers restores completely the activity. Circular dichroism measurements show that the secondary/tertiary structure organization of each subunit is unaffected by the SDS concentration, while the mutation Phe/Trp causes weakening in quaternary structure. The presence of the strong human CDA competitive inhibitor 5-fluorozebularine disfavours dissociation of the tetramer into subunits in the wild-type CDA, but not in mutant enzyme F137W/W113F. The absence of tyrosine fluorescence and the much higher quantum yield of the double mutant protein spectrum suggest the occurrence of an energy transfer effect between the protein subunits. This assumption is confirmed by the crystallographic studies on B.subtilis in which it is shown that three different subunits concur with the formation of each of the four active sites and that F125, homologous to the human CDA F137, is located at the interface between two different subunits contributing to the formation of active site.

Cytidine deaminase (CDA) purified from human placenta revealed the presence of five isoenzymatic forms that differ only in their isoelectric point. Since human cytidine deaminase exists in two variants (CDA 1 and CDA 2) with a non-conservative amino acid substitution at codon 27, in this work we demonstrate that these two variants may combine together in vitro, giving five CDA isoforms as observed in vivo from human placenta. For this purpose, each of the two forms of CDA was purified close to homogeneity and dissociated into monomers in the presence of a small amount of sodium dodecyl sulfate as a dissociating agent. The monomers were mixed together and subjected to anion-exchange chromatography and to chromatofocusing analysis in order to visualize the formation of the five isoforms. Furthermore, for both CDA 1 and CDA 2 some substrates and inhibitors of CDA were assayed, with the aim of demonstrating different kinetic behavior between the two natural variants.

Milk is one of the most common causes of food allergies among children under one year of age. No specific therapy exists for this allergy, and thus the only feasible response is to avoid assumption of milk and derived products. Studies conducted on the serum of children with hypersensi- tivity to milk have shown that caseins are the proteins with the greater allergenic potential. However, in some cases, children have also shown hypersensitivity to the β-lactoglobulines and to the α-lactal- bumins. When food intolerance is diagnosed in an infant, it is often necessary to impose a period of total parenteral feeding, followed by breast feeding, considered the most correct method of re-feeding. When human milk can not be given, alternative food sources must be sought. Clinical studies have demonstrated that donkey milk could substitute breast feeding in infants affected by severe Ig-E me- diated milk allergies. In these subjects, donkey milk is not only useful, but also safer than other types of milk. In fact donkey milk composition in lipids (high levels of linoleic and linolenic acid) and pro- teins (low caseins content) is very close to human milk. Lysozyme content in donkey milk resulted to be very high (mean value 1.0 mg/ml) if compared to bovine (traces), caprine (traces) and human milk. The high lysozyme content of donkey milk may be responsible of the low bacterial count reported in literature and also makes this milk suitable to prevent intestine infections to infants. Among seropro- teins, β-lactoglobulin and α-lactalbumin content in donkey milk was respectively 3.75 and 1.80 mg/ml and remained substancially the same during the different stages of lactation.