Distribution of TAS2R38 bitter taste receptor phenotype and haplotypes among COVID-19 patients.

Bitter taste receptor TAS2R38 is expressed in the respiratory tract and can respond to quorum-sensing molecules produced by pathogens, stimulating the release of nitric oxide, with biocidal activity. TAS2R38 presents two main high-frequency haplotypes: the "taster" PAV and the "non-taster" AVI. Individuals carrying the AVI allele could be at greater risk of infections, including SARS-CoV-2. The aim of this study was to assess the frequency of PAV and AVI alleles in COVID-19 patients with severe or non-severe symptoms compared to healthy subjects to further corroborate, or not, the hypothesis that the PAV allele may act as a protecting factor towards SARS-CoV-2 infection while the AVI one may represent a risk factor. After careful selection, 54 individuals were included in the study and underwent genetic analysis and PROP phenotype assessment. Our investigation could not point out at a significant relationship between single nucleotide polymorphisms responsible for PROP bitterness and presence/severity of SARS-CoV-2 infection, as previous studies suggested. Our results uncouple the direct genetic contribution of rs10246939, rs1726866 and rs713598 on COVID-19, calling for caution when proposing a treatment based on TAS2R38 phenotypes.

The efficacy of myofunctional therapy in patients with atypical swallowing.

PURPOSE: The myofunctional treatment (MFT) is a conventional therapy in the treatment of oral disease like atypical swallowing (AS). Functional (standardized surface electromyographic analysis-ssEMG) and clinical ("orofacial muscular evaluation with score" protocol-OMES) analyses were conducted to detect the effects of MFT (10 weeks session) in a group of patients with AS. METHODS: ssEMG was performed to analyze the activity of masseter (MM), temporalis (TA), and submental (SM) muscles before (T1) and after (T2) the MFT in a group of 15 patients. OMES was completed at the same timepoints. A Student-t test was carried out to detect differences between T1 and T2 for ssEMG data, and a signed RANK test was used for OMES ones. One-way ANOVA variance test was performed to detect any differences between the different couples of muscles at each timepoint. RESULTS: After MFT, patients showed a shorter duration of the whole act of swallowing (p < .0001), higher intensity of the SM activity (p < .01) than at T1. At T2 masticatory muscles showed lower values for the activation index (ANOVA, p < .0001) and for the spike position (ANOVA, p < .01) than SM. The OMES protocol showed a significant increase for the total evaluation score (p < .01), appearance-posture (p < .01) and functions (p < .001). CONCLUSIONS: MFT permits a shortening of the muscular activation pattern and an increase in SM activity. The improvement of oral functionalities is possible and identifiable thanks to the use of standardized protocols.

Preclinical study for treatment of hypospadias by advanced therapy medicinal products.

PURPOSE: This paper explores the feasibility of a new therapy for the treatment of hypospadias patients. Hypospadias is a very common congenital malformation of male genitals, with very high rate of recurrences after surgery. The field of regenerative medicine, which offers innovative solutions for many pathologies, still does not offer reliable solution for this pathology. Here, we propose quality, safety, and clinical feasibility assessment for an oral mucosa advanced therapy medicinal product (ATMP) grown on a biocompatible scaffold for a clinical study on urethral reconstruction of hypospadias patients. METHODS: Urethral and oral mucosal epithelia from donor biopsies were cultivated between two fibrin layers, under clinical-grade conditions for cell and tissue characterization and comparison, aimed at tissue engineering. In addition, single-clone analyses were performed to analyze gene expression profiles of the two epithelia by microarray technology. RESULTS: Oral mucosa appeared suitable for urethral reconstruction. The resulting ATMP was proven to maintain stem cells and regenerative potency. The preclinical safety studies were performed on human tissues to assess abnormalities and tumorigenicity, and confirmed the safety of the ATMP. Finally, the patient selection and the clinical protocol for the upcoming clinical trial were defined. CONCLUSIONS: Against this backdrop, in this paper, we are proposing a new reproducible and reliable ATMP for the treatment of hypospadias.

A new method to assess foveal morphology with optical coherence tomography.

PURPOSE: To measure foveal morphology using optical coherence tomography (OCT). METHODS: Three examiners classified normal subjects and patients with macular edema and epiretinal membranes from a normative database (299 OCT scans) and a study sample (80 OCT scans) on the basis of the foveal depression appearance (reference classification). The following parameters were measured for each OCT scan: Central Foveal Thickness (CFT), Central Subfield Thickness (CST), Central Subfield Volume (CSV), Centrofoveal Index (CI), Parafoveal Index (PI), and Foveal Indices (FI1, FI2, FI3). Foveal depression of OCT scans in the study sample were classified based on the values of OCT parameters using Bayesian statistics (test classifications). RESULTS: Agreement between reference and test classifications was of 70% for CFT, 58.7% for CST, 60% for CSV, 80% for CI, 72.5% for PI, 88.7% for FI1, 96.2% for FI2 and 97.5% for FI3. CONCLUSIONS: IF3 seems to provide a reliable measure of the foveal morphology.

Approaches for Effective Clinical Application of Stem Cell Transplantation.

PURPOSE OF REVIEW: This review highlights problems related to translation of advanced therapy medicinal products (ATMPs) from bench to bedsite. Regenerative medicine within the current regulatory frame reveals common hitches in the course of development, translation, and clinical application. This paper suggests outlining a path from the few examples of successfully approved vs unsuccessful advanced therapies. RECENT FINDINGS: In the multitude of ongoing studies, few of them achieved positive results with a final treatment available to patients; this result was possible due to multidisciplinary teams working together from the beginning of the development and during the hard route to standardization and clinical application. SUMMARY: The root of success of an advanced therapy requires not only the inescapable scientific and biological knowledge but also requires several contributions as regulatory, ethical, medical, and bio-engineering expertise, from the real beginning. A strong scientific rationale and an integrated network of expertises would contribute to a successful investment of available resources in advanced therapy medicinal products and to a greater confidence in future medicine.

Preliminary approach for the surface electromyographical evaluation of the oral phase of swallowing.

Swallowing is a muscular activity that occurs both after mastication and spontaneously as a result of saliva accumulation. Spontaneous saliva swallowing occurs about every 2 minutes. Comprehension of its functional mechanisms is relevant to assess their modification in clinical situations. A standardised surface electromyographical (ssEMG) protocol for the evaluation of this muscle activity is lacking. Aims of the present study are: (i) to determine the reproducibility of a ssEMG protocol for the evaluation of the oral phase of saliva swallowing and (ii) to evaluate the activity of masseter (MM), anterior temporalis (TA), submental muscles (SM) to draw a reference model of swallowing. Standardised surface electromyographical activity of MM, TA and SM during swallowing of saliva spontaneously accumulated was recorded in 20 healthy participants. Functional indexes including symmetry (POC), recruitment (Impact), duration of activation of each couple of muscles and of the whole exercise, position, intensity of the spike were computed. Inter- and intra-appointment reliabilities were assessed and method errors calculated. Descriptive statistics, sex- and muscles-related comparisons were carried out. Standardised surface electromyographical assessment of MM, TA and SM muscles was reliable. A high inter-individual variability was found. Percentage overlapping coefficient (POC) values were close to 80% for TA and SM, higher than for MM (P < .001). Impact values ranged between 16.4% and 30.7%, and differences were found between muscles (P < .001). The global muscle activity during swallowing lasted between 1.5 and 1.8 seconds. For each couple of muscles, the duration of activation ranged between 0.7 and 1.6 seconds and muscles-related differences were found (P < .001). The spike of activation for each couple of muscle ranged between 35.7% and 44.2% of the duration. The protocol was reliable and intra-participants repeatable measures can be carried out. Due to the high inter-participants variability, further analyses are needed to draw a model of muscular activity.

Craniofacial structures' development in prenatal period: An MRI study.

INTRODUCTION: The development of skeletal structures (cranial base, upper and lower) and upper airways spaces (oropharyngeal and nasopharyngeal) of the skull has always been an issue of great interest in orthodontics. Foetal MRI images obtained as screening exam during pregnancy can help to understand the development of these structures using a sample cephalometric analysis. MATERIAL AND METHODS: A total of 28 MRI images in sagittal section of foetuses from 20th to 32th weeks of gestation were obtained to dispel doubts about the presence of skeletal malformations. Cephalometric measurements were performed on MRI T2-dependent images acquired with a 1.5 T scanner. The Software Osirix 5 permits to study sagittal and vertical dimensions of the skull analysing linear measurements, angles and areas of the skeletal structures. RESULTS: Vertical and sagittal dimension of cranial base, maxilla and mandible grow significantly (P < .01) between the second and third trimester of gestational period as well as nasopharyngeal and oropharyngeal spaces (P < .05). High correlation between the development of anterior cranial base and functional areas devoted to speech and swallow is demonstrated (r: .97). CONCLUSIONS: The development of craniofacial structures during foetal period seems to show a close correlation between skeletal features and functional spaces with a peak between the second and third trimester of gestation. MRI images result helpful for the clinician to detect with a sample cephalometric analysis anomalies of skeletal and functional structures during prenatal period.

Polarization properties of second-harmonic generation in AlGaAs optical nanoantennas.

Manipulating light at the nanoscale by means of dielectric nanoantennas recently received renewed attention thanks to the development of key enabling fabrication tools in semiconductor technology, combined with the extremely low losses exhibited by dielectrics in the optical regime. Nanostructures based on III-V type semiconductors, characterized by an intrinsic broken symmetry down to a single elementary cell, has already demonstrated remarkable nonlinear conversion efficiencies at scales well below the operating wavelength. In this Letter, we thoroughly investigate the emission properties of second-harmonic generation (SHG) in AlGaAs monolithic nanoantennas. Our findings point toward the pivotal role of volume susceptibility in SHG, further unraveling the physics behind the nonlinear processes in these systems. The extremely high SHG efficiency attained, together with the control over the polarized emission in these nanoantennas, constitute key ingredients for the development of tunable nonlinear metasurfaces.

Local wound healing biomarkers for real-time assessment of periodontal regeneration: pilot study.

BACKGROUND AND OBJECTIVES: Within the same surgical procedure, a great variability on achievement of clinical outcomes exists and may be associated to different molecular factors related to tissue healing. The aim of the present study was to assess the distribution of clinical success separately in regenerative therapy (REG) and open flap debridement (OFD) to evaluate if factors related with healing of epithelium, connective tissue and bone may be associated to the clinical outcome within each surgical procedure. MATERIAL AND METHODS: Sixteen patients underwent periodontal REG and nine patients underwent OFD. Periodontal wound fluid was collected at baseline, 3-5, 7, 14 and 21 d after surgery, and expression of wound healing proteins was assessed. Pocket depth and clinical attachment level were taken at baseline and at 6 mo of follow-up. Percentage pocket depth reduction and percentage clinical attachment level gain were computed. Patients were regarded as better or worse responders depending on their percentage pocket depth reduction or percentage clinical attachment level gain. RESULTS: Higher percentage of better responders was observed in the REG group (68.7%) compared to the OFD group (22.2%). At 21 d, no difference in the profile of most of the proteins emerged, with two exceptions, both regarding REG treatment. Bone morphogenetic protein-7 tended to increase in better responders and to decrease in worse responders. Matrix metalloproteinase-1 increased in worse responders and remained substantially unchanged in better responders. CONCLUSION: Local expression of matrix metalloproteinase-1 and bone morphogenetic protein-7 during wound healing is associated with the clinical performance of periodontal regenerative surgery. The use of local biomarkers offers the potential for real-time assessment of the periodontal healing process.

Measurement of carbon ion microdosimetric distributions with ultrathin 3D silicon diodes.

The commissioning of an ion beam for hadrontherapy requires the evaluation of the biologically weighted effective dose that results from the microdosimetric properties of the therapy beam. The spectra of the energy imparted at cellular and sub-cellular scales are fundamental to the determination of the biological effect of the beam. These magnitudes are related to the microdosimetric distributions of the ion beam at different points along the beam path. This work is dedicated to the measurement of microdosimetric spectra at several depths in the central axis of a (12)C beam with an energy of 94.98 AMeV using a novel 3D ultrathin silicon diode detector. Data is compared with Monte Carlo calculations providing an excellent agreement (deviations are less than 2% for the most probable lineal energy value) up to the Bragg peak. The results show the feasibility to determine with high precision the lineal energy transfer spectrum of a hadrontherapy beam with these silicon devices.

Oral health in young women having a low calcium and vitamin D nutritional status.

OBJECTIVE: Oral health plays an important role in an individual's eating choices, which in turn ensure good nutrition throughout life. The deterioration in diet quality may partially explain the association between tooth loss and several systemic diseases, including osteoporosis. The study evaluated the association between oral health and calcium (Ca) and vitamin D nutritional status. The effect of several dietary and lifestyle habits was also evaluated. MATERIAL AND METHODS: One hundred six women aged 23.7 ± 0.4 years were evaluated. Ca intake (CaI) and protein intake were recorded, and 25-hydroxyvitamin D (25OHD) was evaluated. Dental status and caries risk were assessed by determining the number of decayed (D), missing (M), and filled (F) teeth and DMFT index, Löe Silness plaque index (PI), and sugar intake (SI). RESULTS: Deficient CaI was observed in 59% of women; 71% had 25OHD <30 ng/mL and 72% consumed soft drinks daily. M/T score was 3%, D/T score was 28.4%, and F/T score was 0%. Thirty-nine percent of women were missing at least one tooth. PI and SI were 2.0 ± 0.1 and 5.2 ± 0, respectively, and DMFT score was 6.6 ± 0.4. CaI adjusted by other risk factors was associated with higher percentage of caries (p < 0.0001), DMFT (p < 0.001), and PI (p < 0.007). One hundred percent of women presented gingivitis. When considering the one third of the studied group with the highest caries scores, DMFT reached 10.6 ± 0.5. This group had significantly lower CaI and 25OHD levels (p < 0.05) and significantly higher protein intake, daily consumption of soft drinks, and PI and SI values compared to the rest of the women (p < 0.05). CONCLUSION: The results of this cross-sectional report evidenced an association between high cariogenic risk and great severity of oral disease in the studied group of young women and low CaI. CLINICAL RELEVANCE: Although caries progression is a complex process involving multiple factors, an adequate nutritional status of Ca and vitamin D could be an additional factor that may help preserve a good oral health.

Neutron measurements with ultra-thin 3D silicon sensors in a radiotherapy treatment room using a Siemens PRIMUS linac.

The accurate detection and dosimetry of neutrons in mixed and pulsed radiation fields is a demanding instrumental issue with great interest both for the industrial and medical communities. In recent studies of neutron contamination around medical linacs, there is a growing concern about the secondary cancer risk for radiotherapy patients undergoing treatment in photon modalities at energies greater than 6 MV. In this work we present a promising alternative to standard detectors with an active method to measure neutrons around a medical linac using a novel ultra-thin silicon detector with 3D electrodes adapted for neutron detection. The active volume of this planar device is only 10 µm thick, allowing a high gamma rejection, which is necessary to discriminate the neutron signal in the radiotherapy peripheral radiation field with a high gamma background. Different tests have been performed in a clinical facility using a Siemens PRIMUS linac at 6 and 15 MV. The results show a good thermal neutron detection efficiency around 2% and a high gamma rejection factor.

Serum factors associated with precancerous colonic lesions in acromegaly.

BACKGROUND: Insulin, 25-hydroxy vitamin D3 [25(OH)D3] and folate have been differently associated with a risk of colonic neoplasms in the general population. Acromegalic patients have an increased risk of colorectal tumors and an association between fasting insulin concentrations and colonic lesions has been reported. However, it is unknown whether insulin, 25(OH)D3, folate, and homocysteine interact to determine the risk of colonic tumors in acromegaly. AIM: To investigate whether serum insulin, 25(OH)D3, folate, and homocysteine concentrations were associated with precancerous colonic lesions in acromegalic patients. MATERIAL AND METHODS: A cohort of 146 consecutive acromegalic patients was evaluated for colonoscopy findings and fasting insulin, 25(OH)D3, folate, and homocysteine levels. A preliminary study was conducted in 9 naïve acromegalic patients to evaluate the effect of somatostatin analogues (SSA) on serum levels of those factors. RESULTS: Insulin reduced during SSA whereas the other factors did not change. In the cohort study, colonic lesions (14 adenomas; 32 hyperplastic polyps) were detected in 46 patients. Fasting insulin, 25(OH)D3, folate, and homocysteine levels did not differ in patients with or without colonic adenomas. High folate levels were associated with a lower risk of developing precancerous colonic lesions at the multivariate analysis, when corrected by age, gender, disease activity and SSA therapy. CONCLUSIONS: Serum insulin, 25(OH)D3 and homocysteine serum concentrations do not seem to influence the development of precancerous colonic lesions in acromegalic patients, while higher folate levels may be associated with a lower risk of colonic lesions.

Management of paediatric Lyme disease in non-endemic and endemic areas: data from the Registry of the Italian Society for Pediatric Infectious Diseases.

The purpose of this investigation was to determine how specialists in paediatric infectious diseases (PIDs) manage children with suspected Lyme disease (LD) by comparing their approaches in Italian endemic and non-endemic areas. A cross-sectional survey of the PID specialists participating in the Italian Society for Pediatric Infectious Disease (SITIP) Registry of LD was carried out between 1 January and 30 April 2012. A total of 160 children (80 living in endemic areas and 80 living in non-endemic areas) were diagnosed as having LD between 1 January 2005 and 31 December 2011. The clinical manifestations were erythema migrans in 130 cases (81.3 %), arthritis in 24 (15.0 %) and neuroborreliosis in six (3.8 %). Significant differences from the recommendations concerning serology and the tests to undertake were mainly observed in the children with erythema migrans, especially those living in non-endemic areas (p < 0.05). The children with erythema migrans who lived in non-endemic areas were treated with antibiotics significantly less frequently than those living in endemic areas (p < 0.05), and significantly fewer children with erythema migrans or arthritis living in non-endemic areas were treated with amoxicillin in comparison with those living in endemic regions (p < 0.05). The duration of antimicrobial therapy was significantly shorter than recommended in the children with erythema migrans or arthritis, especially those living in non-endemic areas (p < 0.05). Paediatric LD is also present in areas of Italy in which it is not considered endemic, but knowledge concerning its management is generally poor among PID specialists and characterised by enormous gaps in non-endemic areas.

In vivo early plaque formation on zirconia and feldspathic ceramic.

AIM: Zirconia is a ceramic material with optimal aesthetic and mechanical properties that make it adapt to esthetic recontructions in narrow spaces. Aim of this split mouth clinical trial is to compare amount and structure of early plaque coated to zirconia and feldspathic ceramic. METHODS: Four patients were included in this study. A removable acrylic device was manufactured for each subject and equipped on the lingual surface in correspondence to molar teeth with eight specimens. Four zirconia samples were positioned on the right side (test) of the device, and 4 feldspathic ceramic samples were positioned on the left side (control). One test and one control samples were harvested from each device at 6, 12, 24 and 36 hours after oral environment exposition. A total of four samples for each group were collected at each timepoint; three of these were used for reverse transcription polymerase chain reaction analysis to evaluate the bacteria plaque amount; the remaining sample was used for scanning electron microscopy analysis to observe the bacteria plaque structure. RESULTS: No significant differences were detected in terms of bacteria amount between test and control group at each timepoint. At scanning electron microscopy evaluation especially at 36 hou, bacteria plaque structure coated to zirconia surface appeared less uniform and compact compared to feldspathic ceramic. CONCLUSION: Zirconia material may be considered adapt to prosthetic reconstructions that require high mechanical and aesthetic properties and that are exposed to the oral environment.

Synthesis of ZnO nanostructures using different metal catalyst: morphology and photoluminescence characteristics.

In the present study, we report the synthesis of ZnO nanostructures using the Vapor-Liquid-Solid growth with different metal catalyst by electron beam evaporation method. As grown samples were characterized by means of Field emission scanning electron microscopy (FESEM), Raman spectroscopy and photoluminescence spectroscopy. FESEM characterization showed the formation of different type of nanostructure depending on the metal catalyst. Array of well aligned nanorods were formed when Au and Fe were used as a catalyst. However, Sn catalyst induced the formation of nanoflakes. The presence of peak at 434 cm(-1) in Raman spectroscopy revealed the wurtzite nature of formed ZnO nanostructures. Nanoflakes showed a more strong UV emission in comparision to that of nanorods as revealed by Photoluminescence spectra.

PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration.

Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5 x 10(8) or 5.5 x 10(9) pfu ml(-1)), Ad encoding luciferase (Ad-Luc; 5.5 x 10(9) pfu ml(-1); control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg ml(-1)). Bone repair and osseointegration were measured through backscattered scanning electron microscopy, histomorphometry, micro-computed tomography and biomechanical assessments. Furthermore, a panel of local and systemic safety assessments was performed. Results indicated that bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared with Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B shows regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable with rhPDGF-BB protein delivery in vivo.

Pre-clinical models for oral and periodontal reconstructive therapies.

The development of new medical formulations (NMF) for reconstructive therapies has considerably improved the available treatment options for individuals requiring periodontal repair or oral implant rehabilitation. Progress in tissue engineering and regenerative medicine modalities strongly depends on validated pre-clinical research. Pre-clinical testing has contributed to the recent approval of NMF such as GEM 21S and INFUSE bone grafts for periodontal and oral regenerative therapies. However, the selection of a suitable pre-clinical model for evaluation of the safety and efficacy of a NMF remains a challenge. This review is designed to serve as a primer to choose the appropriate pre-clinical models for the evaluation of NMF in situations requiring periodontal or oral reconstruction. Here, we summarize commonly used pre-clinical models and provide examples of screening and functional studies of NMF that can be translated into clinical use.

Cutaneous melanoma with metastasis in a cynomolgus monkey (Macaca fascicularis).

BACKGROUND: A 3.3-year-old-male cynomolgus macaque (Macaca fascicularis) showed a focally extensive soft, dark, discoid dermal mass, 0.5 cm in diameter, on the dorsal surface of the right hind foot, over the fourth and fifth metatarsal bones. METHODS AND RESULTS Microscopic examination revealed a cutaneous melanoma with local lymphatic invasion, characterized by neoplastic melanocytes within the subcapsular sinus of popliteal and inguinal lymph nodes. The diagnosis was confirmed by immunohistochemistry and transmission electron microscopy. CONCLUSIONS: To our knowledge, this is the first documented case of melanoma in a cynomolgus monkey.

Gene therapy of inherited skin adhesion disorders: a critical overview.

Gene therapy has the potential to treat devastating inherited diseases for which there is little hope of finding a conventional cure. These include lethal diseases, like immunodeficiencies or several metabolic disorders, or conditions associated with a relatively long life expectancy but poor quality of life and expensive and life-long symptomatic treatments, such as muscular dystrophy, cystic fibrosis and thalassaemia. Skin adhesion defects belong to both groups. For the nonlethal forms, gene therapy, or transplantation of cultured skin derived from genetically corrected epidermal stem cells, represents a very attractive therapeutic option, and potentially a definitive treatment. Recent advances in gene transfer and stem cell culture technology are making this option closer than ever. This paper critically reviews the progress and prospects of gene therapy for epidermolysis bullosa, and the technical and nontechnical factors currently limiting its development.