Background. Many anticancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (compound B) showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds, in comparison with 4 popular anticancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one-order of magnitude higher TSM as compared with newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two order of magnitude lower TSE than compounds A and B. Compounds A and B showed higher TSM, TSE and TSN values than doxorubicin, 5-FU and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that compounds A and B may inhibit the signaling pathway of estrogen-related receptors.

Oral squamous cell carcinoma often arises from an oral potentially malignant disorder called oral leukoplakia (OL). With this work we aimed to develop a novel data-driven predictive model based on gene expression profiles to distinguish OL patients who underwent malignant transformation from those who did not. We used the Tree Augmented Naïve (TAN) Bayes classifier to predict the posterior probability of having oral cancer given the data. 86 patients were included with a median follow-up of 7.11 years. Fifty-one patients (51/86; 59%) underwent malignant transformation. We found that 16 genes were predictors of oral cancer in patients with OL and these included SLC7A11, SPINK6, SERPINA12, VIT, ATP1B3, CST6, FLRT2, ELMOD1, AZGP1, RNASE13, DIO2, ECM1, CYP4F11, SYTL4, AKR1C1, and AKR1C3. In conclusion, we showed that Bayesian gene networks are a data-driven approach which could be used also in other predictor models in oncology.

Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, Middle East and USA areas. While in the ancient time pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, up to consider pomegranate as a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs) and its consumption appears to exert numerous healthy beneficial effects, in particular, in several pathological conditions, namely in patients affected by metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and in dentistry represents a promising field, as it could permit the development of innovative natural adjuvant therapies, able to empower the standard pharmaceutical therapies.

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, USFDA has given expedited approval to bedaquiline (BDQ), as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis but due to poor solubility desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of Bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of Bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88±2.1 nm with a zeta potential of 21.16 mV. In vitro, studies showed enhanced drug release with a high degree of stability at 25 ± 2 ºC & 60 ± 5 % and 40 ± 2 ºC & 75± 5 %. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.

Total edentulism is the loss of all teeth for any cause by a multifactorial process that involves biological and patient-related factors. Studies on edentulism and risk factors in Mexico are limited, and the epidemiological surveillance data is scarce and controversial since official governmental reports are not statistically representative of the country. We estimate the distribution for edentulism according to sociodemographic and socioeconomic variables in adults from a low-income state in 2003 and its progress in Mexico. We analyzed data from the National Performance Evaluation Survey in Oaxaca, Mexico, and the annual reports of the Epidemiological Surveillance System of Oral Pathologies in 2009-2019 using X². Oaxacan patients older than 75 y.o (17.9%, p<0.05), those with lower schooling (11.2%), and diabetes (14.5%) presented the highest percentage of edentulism. We do not observe differences in edentulism between sex or residence (p>0.05). From 2009 to 2019, country data reports the lowest rate of edentulism in adults over 20 y.o (0.32%; 95% CI 0.18%-0.48%) and the most affected population over 79 y.o. (7.29%; 95% CI 5.2%-9.30%). As it is a cumulative phenomenon, it is necessary to establish better surveillance, prevention, and treatment programs to improve the oral health of older thus reducing edentulism.

Introduction: In the recent years alternate day dosing has been recommended in iron deficieny treatment. The aim of this study is to compare the efficacy and side effects of oral iron treatments given daily 1x1, alternate day 1x1 and 2x1 alternate day dosing in iron deficieny anemia patients. Methods: A total of 52 patients with a diagnosis of iron deficiency anemia with serum ferritin level of 25 µg/L or less were included in this retrospective study. Statistical analyzes were done with SPSS V.25. Results: The patients included in our study were between the ages of 18-51. All of the patients included in the study were female. A statistically significant increase was found between 0-14 days(p<0.001), 14-28 days(p<0.001) and 0-28 days(p<0.001) hemoglobin values in all patients. There was no statistically significant difference between 0-14 days (p=0.397) and 0-28 days(p=0.310) ferritin values in all patients. A statistically significant difference was found between 14-28 days(p<0.001) ferritin values. When the rate of change of hemoglobin and ferritin values between the groups was compared and no statistically significant difference was observed between the groups. The rate of change of ferritin values for 14-28 days was significant (p=0.012). There was no significant difference in the frequency of symptoms in the 14th day and 28th day controls for each group (p>0.05). The incidence of metallic taste and bloating symptoms was found to be statistically significant in the third control in the group with 2x1 drug use alternate day (p=0.094). Discussion: The only difference in efficacy was observed in ferritin values between 14th and 28th days. The increase in ferritin values was higher in the group that used 1x1 oral iron every day. However, since no difference was observed between the groups in terms of ferritin and hemoglobin values on days 0 and 28, all three groups were considered equally efficient. Side effects were mainly gastrointestinal side effects. Since the group that received 2x1 oral treatment alternate day had a statistically significantly higher rate of side effects, the patients’ treatment tolerance will be lower compared to the other groups. In conlusion, there is no difference in efficacy and side effects between the patient groups receiving 1x1 daily and 1x1 alternate day oral iron therapy, so 1x1 use alternate day is the most appropriate treatment method for oral iron therapy in terms of patient tolerance, adherence to treatment and pharmacoeconomics.

The proportion of human cells to the microbial cell is 1:1. These procaryotes use efflux pumps and enzymes to prevent cellular intoxication of ions and compounds respectively. There is promising evidence on the role of the gut microbiome and its enzymes in metabolizing xenobiotics. The genetic potential of oral bacteria in drug and xenobiotic metabolism is yet to be unveiled. This study aimed to characterize the bacteriome associated with oral fibroepithelial polyps (FEP) and to predict the genetic potential. A representative sub-sample of 22 clinically diagnosed oral FEP (the control group) was selected from a main case-control study. Amplification of nucleotides of extracted DNA from frozen tissues was performed for the V1 to V3 region and sequencing of the amplicon with Illumina’s 2 X 300–bp chemistry. Classification of high-quality nonchimeric merged reads was done to the species level with a prioritized BLASTN-based algorithm. Downstream compositional analysis was performed with QIIME (Quantitative Insights into Microbial Ecology). Functional prediction of bacteriome was obtained by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States). Rothia mucilaginosa, Streptococcus mitis, Gamella haemolysans, Streptococcus sp. oral taxon 431, and Rothia dentocariosa accounted for the top five taxa among 810 bacterial species according to the percentage of average relative abundance. Rothia mucilaginosa was elevated statistically significantly (p< 0.05). The genetic potential of xenobiotics and drug metabolism catalyzed by the P450 enzymes was observed for the first time as an attribute of bacteriome associated with oral FEP tissues dominated by R. mucilaginosa. This finding needs further investigation.

Abstract: Cherubism is a rare genetic disorder characterized by painless bilateral expansion of the mandible and maxilla. We present an unusual case of a 50-year-old female patient with Ramon syndrome, a rare variant of cherubism, accompanied by gingival fibromatosis. The patient exhibited symptoms of short stature, mental retardation, rheumatoid arthritis, epilepsy, hirsutism, and gingival enlargement. Clinical examination revealed generalized gingival inflammation with plaque and attachment loss. Radiographically, bilateral defined multilocular radiolucencies were observed in the mandibular body and ramus. The patient underwent a non-surgical phase, including oral hygiene motivation and periodontal debridement, followed by a surgical phase involving gingivoplasty and internal bevel gingivectomy with open flap debridement. Histopathological analysis confirmed the presence of fibroblasts, multinucleated giant cells, and fibrous connective tissue. The patient's son also presented with bilateral facial swelling and similar radiographic findings, indicating familial inheritance of cherubism. The case demonstrates the clinical, radiographic, and histopathological features of cherubism associated with gingival fibromatosis and highlights the challenges in diagnosis and management. Regular follow-up and maintenance are essential for long-term stability and prevention of recurrence. This report contributes to the limited literature on cherubism in older patients and emphasizes the importance of early identification and intervention in affected individuals.

Background: COVID-19 represents a threat for frailty patients. Objective: Investigate efficacy, safety and economic value of treatment with Molnupiravir in a cohort of fragile patients affected by COVID-19. Methods: Observational, prospective study. The data collected allowed to assess efficacy and safety of Molnupiravir in real life, compare the results with a subgroup of patients treated with Nirmatrelvir-Ritonavir and to effect a cost-effectiveness analysis. Results: In January-December 2022, 435 patients (225 males, 220 females; median age 72 years), were enrolled; 24 patients were unvaccinated, 280 patients had ≥2 risk factors. Molnupiravir appeared to give better results than the SOC both clinically and economically. In these patients in comparison with literature data or SOC, hospitalization was 2.5% vs 6.8% (p&lt;0.005), overall adverse effects 14,3% vs 30.4% (p&lt;0.0001), severe adverse effects 2.6 vs 6.9% (p&lt;0.001), thus involving a potential total savings of about € 92.954 per patient (8% of standard of care cost). Conclusions: early Molnupiravir treatment helped fragile patients who partially responded to vaccine, or with absolute contraindications to vaccination, to overcome COVID-19 without the need of hospitalization. Molnupiravir represents a clinical and economic effective treatment, avoiding disease progression in old patients suffering from multiple pathologies and taking several drugs.

The aims of this study are to determine the oral health status of a rare sample of 19th-century migrant settlers to South Australia, how oral conditions may have influenced their general health, and how the oral health of this group compares with contemporaneous samples in Australia, New Zealand, and Britain. Dentitions of 18 adults and 22 subadults were investigated using non-destructive methods (micro-CT, macroscopic, radiographic). Extensive carious lesions were identified in 17 adults and 4 subadults, from this group 1 subadult and 16 adults had antemortem tooth loss. Sixteen adults showed evidence of periodontal disease. Enamel hypoplastic (EH) defects were identified in 14 adults and 9 subadults. Many individuals with dental defects also had skeletal signs of co-morbidities. South Australian individuals had the same percentage of carious lesions as the British sample (53%), more than other historic Australian samples, but less than a contemporary New Zealand sample. Over 50% of individuals from all the historic cemeteries had EH defects suggesting systemic health insults during dental development were common during the 19th century. The overall oral health of the South Australian settlers was poor but, in some categories, (tooth wear, periapical abscess, periodontal disease), better than the other historic samples.

Introduction: Osteosarcomas of the jaw (OSJ) are rare tumors with a different behavior from osteosarcomas of other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of this type of sarcoma. Methods: a retrospective observational study of cases diagnosed with OSJ registered at the “La Paz” University Hospital (Madrid). Results: Eight cases with a diagnosis of OSJ were obtained in a study period of 22 years (2000-2022). The mean age was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most common. Survival at 5 years was 50%, while at 10 years, it decreased to 25%. Conclusions: OSJ differs from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment; more studies are needed in which more standardized protocols can be proposed for adjuvant therapeutic management.

Objectives and Background: Gestational diabetes (GDM) is a common pregnancy complication, defined as a glucose intolerance diagnosis during pregnancy. GDM is strongly associated with adverse fetal and maternal outcomes. In Germany, to screen and diagnose GDM we use a 1-hour 50g oGCT (oral glucose challenge test) followed by a 2-hour 75g oGTT if the first was pathological. This analysis examines the correlation of 75g oGTT glucose levels and fetomaternal outcome. Methods: Data of 1664 patients from a gestational diabetes consultation clinic at the Charité University hospital in Berlin, Germany, were analyzed retrospectively from 2015 until 2022. The 75g oGTT blood glucose levels were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated post-load hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1-hour and 2-hour values after glucose application. These subtypes were compared regarding baseline characteristics as well as fetal and maternal outcome. Results: GDM-IFH and GDM-CH women displayed higher preconceptional BMI and required insulin therapy more frequently (p<0,001). The GDM-IFH group was at higher risk of having a primary cesarean section (p=0,047), while GDM-IPH women were significantly more likely to have an emergent cesarean section (p=0,013). The offspring of GDM-IFH and GDM-CH women were born with a significantly higher mean birthweight (p<0,001) and birth weight percentiles (p<0,001) and were at increased risk of being large for gestational age (LGA) (p=0,004). Women from the GDM-IPH group delivered significantly more neonates who were small for gestational age (p=0,027) or with low fetal weight <30th percentile (p=0,003). Conclusion: This analysis shows a strong association between glucose response pattern in the 75g oGTT and adverse perinatal fetomaternal outcome. The differences among the subgroups, specifically concerning insulin therapy, mode of delivery and fetal growth, suggest an individualized approach in prenatal care after a GDM diagnosis.

The oral health of older individuals can be negatively impacted by various systemic health factors, leading to rapid oral health deterioration. Older people are at risk of experiencing adverse reactions to medications due to multimorbidity, polypharmacy, and changes in pharmacokinetics and pharmacodynamics. Hyposalivation, a significant side effect of some medications, can be induced by both the type and number of medications used. Frailty, disability, sarcopenia, care dependency, and limited access to professional oral healthcare can also compromise the oral health of older people. To prevent rapid oral health deterioration, a comprehensive approach is required that involves effective communication between oral healthcare providers, other healthcare providers, and informal carers. Regardless of their health status, it is crucial to prioritize the well-being of older people. Oral healthcare providers have a responsibility to advocate for the importance of maintaining adequate oral health and to raise awareness of the serious consequences of weakened oral health. By doing so, we can prevent weakened oral health from becoming a geriatric syndrome.

The elderly present age-related morphological and histological changes of the oral cavity; Literature displays many studies regarding the specific pathologies of the oral cavity in elderly patients, but no etiologically based classification is available. The aim of this study was to analyze the series of patients over 65 who were treated by our Unit of Pathology between 2020 and 2022 for a suspicion of oral lesion or for preventive dental evaluation (in anticipation of cardiac surgery, anti-resorptive drugs intake, chemotherapy, radiotherapy of the head-neck district or transplantation). The analysis was conducted by dividing oral lesions into 5 groups depending on the etiology: reactive, immunological, traumatic, benign and malignant degenerative. The sixth group consisted of patients undergoing preventive dental evaluation. The study included 435 patients; 91 of them were diagnosed with a reactive origin pathology, 174 with immunological origin pathology, 48 with traumatic pathology and 86 with degenerative pathology (42 benign and 44 malignant). 36 patients went to our Unit for preventive specialist evaluation. Oral health has a major impact on the daily life of the elderly; The examination of oral mucosa in geriatric patients is a fundamental diagnostic moment to report lesions early, thus allowing easier prevention and treatment.

A newly UHPLC-MS/MS method development and validation for S-Allyl Cysteine was used to evaluate the comparative pharmacokinetic parameters. SC PLGA NPs were developed by the emulsion solvent evaporation method. SC PLGA NPs showed their drug loading and encapsulation efficiency i.e. 5.13±0.10% and 82.36±4.01%, respectively. SC PLGA NPs showed a spherical morphology on an average size (134.8±4.61nm), PDI: 0.277±0.004, and −25.3±1.03mV zeta-potential is suitable for oral delivery. Development and validation of the UHPLC-MS/MS bioanalytical method were performed successfully for PK-parameters examinations with 1.219-minutes RT, MS (162.00/73.10), and a total run-time was 2.0-minutes. 1.0–1000.0ng/mL was a linear-range with inter & intra-day accuracy (92.55–99.40%) followed by precision (1.88–4.23%). SC PLGA NPs oral bioavailability was significantly higher (**p<0.01) as compared to SC-S treated groups (iv & oral). We found that the antimicrobial activity of SC PLGA NPs was more effective than pure S-Allyl-L-Cysteine with significant results (p<0.01) as compared to SC-S. SC PLGA NPs showed fitted physicochemical and enhanced antimicrobial properties which can be helpful for oral administration. On the basis of our observations, SC PLGA NPs suggested the highest potential for the improvement of oral bioavailability with a sustained and controlled release of S-Allyl-L-Cysteine delivery.

Breast cancer is the most common cancer among women worldwide, and estrogen receptor-positive (ER+) breast cancer accounts for a significant proportion of cases. While various treatments are available, endocrine therapies are often the first-line treatment for this type of breast cancer. However, the development of drug resistance poses a significant challenge in managing this disease. ESR1 mutations have been identified as a common mechanism of endocrine therapy resistance in ER+ breast cancer. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has shown some activity against ESR1 mutant tumors. However, due to its poor bioavailability and need for intramuscular injection, it may not be the optimal therapy for patients. Second-generation SERDs have been developed to overcome these limitations. These newer drugs have improved oral bioavailability and pharmacokinetics, making them more convenient and effective for patients. Several oral SERDs are now in phase III trials for early and advanced ER+ breast cancer. This review summarizes the background of oral SERD development, the current status, and future perspectives.

Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and precursor lesions at young ages, mainly at the oral cavity. As patients have defects in DNA repair mechanisms, standard-of-care treatments to OSCC such as radiotherapy and chemotherapy give rise to severe toxicities. New methods for early diagnosis are urgently necessary to allow treatments in early disease stages and achieve better clinical outcomes. We have conducted a prospective, longitudinal study whereby liquid biopsies from sixteen lesion/tumor-free patients were analyzed for the presence of mutations in cancer genes. DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evolution followed during a median time of around 2 years. In 9/16 FA patients we detected mutations in cancer genes (mainly TP53) with molecular allele frequencies (MAF) down to 0.07 %. Importantly, all patients having mutations and clinical follow-up data after mutation detection (n=6) developed oral precursor lesions or OSCC. Lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations display significantly lower risk of developing precursor lesions or OSCC. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow closer surveillance for OSCC or precursor lesions.

The demand for dietary supplements containing collagen has been growing for years. The speciality and uniqueness of the dietary supplement (DS) examined in our study is the presence of L-arginine and hyaluronic acid alongside collagen and vitamin C. The individual mechanisms of action and physiological role of these compounds are understood, but they have not yet been tested in the combination and amounts of the dietary supplement used in this study. In this study, we investigated the effectiveness of the DS in elderly patients with musculoskeletal complaints. Somatometric, body composition, physiotherapy and laboratory tests were performed at the beginning and at the end of the study. The two-month study involved 30 people, randomly divided into two groups: a control group (CG) and an experimental group (EG). All subjects consumed 25 ml DS per day and EG members also participated in physiotherapy 3 times a week. Alongside the DS, blood lipid levels changed: LDL decreased, HDL increased, LDL/HDL ratio significantly decreased in both groups. For EG, the results improved more markedly. In 3 items of the body composition test, there was a significant improvement in both groups, which was attributed to the use of the dietary supplement. For the EG, there were significant changes in 5 additional test items, which we attribute to the addition of regular physical activity. Knee and hip joint range of motion (ROM) showed significant improvements in the study group, while in the CG the DS can cause significant improvements in joint range of motion in a passive condition as well.

Background: Expansion of OKF6/TERT-2 oral epithelial cells in vitro is important for studying the molecular biology of disease and pathology affecting the oral cavity. Keratinocyte Serum-Free Medium (KSFM) is the medium of choice for this cell line. This study compares three media for OKF6/TERT-2 cultures: KSFM, Dulbecco’s Modified Eagle Medium/Nutrient Mixture of Hams F-12 (DMEM/F12) and a composite medium comprised of DMEM/F-12 and KSFM (1:1 v/v), referred as DFK. The toxicological effects of electronic cigarette liquids (E-liquids) on OKF6/TERT-2 cells cultured in these media were also compared. Methods: Cells were cultured in KSFM, DMEM/F12 or DFK and cellular morphology, growth, wound healing and gene expression of mucins and tight junctions were evaluated. Additionally, cytotoxicity was determined after E-liquid exposures. Results: Switching from KSFM to DMEM/F12 or DFK 24-hours post-seeding leads to typical cellular morphologies, and these cultures reach confluency faster than those in KSFM. Wound-healing recovery occurred fastest in DFK. Except for claudin-1, there is no difference in expression of the other genes tested. Additionally, E-liquid cytotoxicity appears to be amplified in DFK cultures. Conclusions: DMEM/F12 and DFK are alternative media for OKF6/TERT-2 cell culture to study molecular biology of disease and pathology, provided cells are initially seeded in KSFM.

Introduction: Some of the practices in medicine are carried out of habit without proven benefits. This is the case of premature babies from 30 to 34 weeks of gestation who are always given parenteral fluids, even though this practice has been associated with an increase incidence of infection. At the end of 2017, we started a protocol of rationalization in the use of parenteral fluid. To administer nutrition/fluids, we used oral fluids by suction if this was possible or otherwise by oral/nasogastric tube at volumes of 70-80 mL/Kg/day divided every 3 hours, with 5 mL increments every 12-24 hours until 200 mL/K/day was achieved, always using breast milk when possible. Material and methods: The present study sought to compare results before and after this new policy. For this work, we review all premature babies between 30-34 weeks of gestation in two time periods, the first from 01/01/2010 to 12/31/2017 and the second from 01/01/2018 to 08/15/2022. The number of cases with and without parenteral fluids (PF), the incidence of infection, the weight at admission and discharge, and the change in the weight Z score between birth and discharge were compared. Both the anthropometric and outcome variables were compared using the different statistical methods according to each variable. Results: were found 920 cases with the described characteristics. The groups before and after the intervention did not show significant differences in their general demographic characteristics. We observed a decrease use of PF in the second period, from 425 cases (82.0%) before to 297 (26.2%) after implementation, p <0.0001 and fewer days of use (4.1 days/average before vs 1.3 after, p <0.0001) of PF. The weight at discharge and the change in weight Z-score were the same in both groups. Infections went from nine cases before to two cases after but it was not statistically significant. There were no complications due to less use of PF. Discussion: This study showed that the use of PF is not associated with significant changes in outcomes of interest, which reinforces that its use does not generate any benefit for the patient. Larger number of cases is required to detect differences in low incidence events such as infections.

Commonly the periodontitis has been linked to periodontopathogens categorized in Socransky's microbial complexes, however, there is a lack of knowledge regarding “other microorganisms” or "cryptic microorganisms", which are rarely thought of as significant oral pathogens and are neither previously categorized nor connected to illnesses in the oral cavity. This study hypothesized that these cryptic microorganisms could contribute to the modulation of oral microbiota present in health or disease (periodontitis and/or OSA patients). For this purpose, the presence and the correlation among these cultivable cryptic oral microorganisms were identified and their possible role in both conditions was determined. Data from oral samples of individuals with or without periodontitis and with or without OSA were obtained from a previous study. Demographic data, clinical oral characteristics, and genera and species of cultivable cryptic oral microorganisms identified by MALDI-TOF were recorded. The data of 75 participants were analyzed to determine the relative frequencies of cultivable cryptic microorganisms’ genus and species, microbial clusters and correlations tests were performed. According to periodontal condition, Gingivitis - dental biofilm-induced in reduced periodontium and stage III periodontitis were found to have the highest diversity of cryptic microorganism species. Based on the experimental condition these findings showed that there are genera related to disease conditions and others related to healthy conditions, with species that could be related to different chronic diseases being highlighted as comorbidities periodontitis and OSA. The cryptic microorganisms within the oral microbiota of patients with periodontitis and OSA are present as potential pathogens, promoting the development of dysbiotic microbiota, and the occurrence of chronic diseases, which have been previously proposed to be common risk factors for periodontitis and OSA. Understanding the function of possible pathogens in the oral microbiota will take more research.

The present study was designed to develop a self-micellizing solid dispersion (SMSD) containing Thymoquinone (TQM), a phytonutrient obtained from Nigella sativa seeds, aiming to improve its biopharmaceutical and nephroprotective functions. The apparent solubility of TQM in polymer solutions was used to choose an appropriate amphiphilic polymer that could be used to make an SMSD system. Based on the apparent solubility, Soluplus® was chosen as an appropriate carrier, and mixing with TQM, SMSD-TQM with different loadings of TQM (5–15%) was made by solvent evaporation and freeze-drying techniques, respectively, and the formulations were optimized. The optimized SMSD-TQM was evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. SMSD-TQM significantly improved the dissolution characteristics (97.8%) of TQM in water within 60 min. Oral administration of SMSD-TQM in rats exhibited a 4.9-fold higher systemic exposure than crystalline TQM. In a cisplatin-induced (6 mg/kg, i.p.) acute kidney-damaged rat model, oral SMSD-TQM (10 mg/kg) improved the nephroprotective effects of TQM based on the results of kidney biomarkers and histological abnormalities. These findings suggest that SMSD-TQM might be efficacious in enhancing the nephroprotective effect of TQM by overcoming biopharmaceutical limitations.

The study of notable people as agents for increasing cancer awareness started just in the last decades of the 20th century. This study aimed to identify Pan-American notable people with head and neck cancer (HNC) and to assess HNC’s professional perspective on communicating stories of notable patients with HNC to promote prevention. Methods: This cross-sectional study was conducted by applying a RedCap questionnaire to oral medicinists, oral pathologists, head and neck surgeons, and clinical oncologists with experience in HNC research, education, or treatment in Pan-American countries. Additionally, a structured search was performed on PubMed, Scopus, EMBASE, Web of Science, LILACS, and gray literature Results: We identified 42 notable people from the United States, Brazil, Argentina, Mexico, El Salvador, Chile, Colombia, and Peru who were mainly actors, athletes, and musicians. Participants agreed that stories of notable patients with HNC can positively impact the population and promote prevention if communicated by the internet, social media, and television. Conclusion: In the Pan-American region, notable individuals who have suffered from HNC may be powerful advocates for increasing cancer awareness and promoting prevention strategies. The professionals involved in the study expressed a positive inclination towards using the stories of these notable HNC survivors as an effective prevention strategy.

Objectives The aim of the study is to evaluate the effectiveness of extra virgin olive oil (EVO) and fruity oil for the treatment of gingivitis. Materials and Methods. A sample of 75 patients with gingivitis induced by plaque bacteria, over 18 years of age, was divided into three groups: a study group A with extra virgin olive oil, a study group B with fruity oil and a control group C. In the two study groups, Evo oil was administered as a mouthwash in patients with gingival inflammation. The protocol included a daily application of the product for 30 days, with three recalls 15 days apart. Clinical parameters of plaque formation and gingivitis - plaque index (PI), bleeding index (BI) were assessed at each recall and scored on a specific periodontal chart. The control group re-ceived no mouthwash treatment to normal daily oral hygiene procedures, and the same clinical parameters as the study group were evaluated. Data were evaluated using SPSS 27.0 software for Windows (SPSS Inc., Chica-go, IL, USA). Then, the pre- and post-treatment values of the groups were compared using the t-student test, set-ting P < 0.05 as the significance level. Results Comparison with the three groups showed that extra virgin olive oil was an adjuvant in the treatment of gingival inflammation, improving PI and BI. In group A, mean plaque index had a 48% reduction and bleeding index 64% reduction, after 30 days. In group B, the mean plaque index had a 35% reduction and a bleeding index reduction of 43%, after 30 days. Conclusion The collected data showed significant improvements in the formation of bacterial plaque and gingi-vitis. the exact mechanism of such treatment is still to be elucidated. As a result of this, further studies with a different sample of patients to those used and a comparison with other products need to be addressed to verify and demonstrate the antibacterial and anti-inflammatory effect of the components of this natural product.

Since the college years represent an important period for forming oral health behaviors during adulthood, it is important that college students establish proper oral health-promoting behaviors. Therefore, this study aims to identify the effects of oral health education experience, knowledge, and practice behaviors on oral health care self-efficacy among college students, as studies related to this topic are scarce. A total of 236 college students participated in a questionnaire survey comprising 21 questions. The collected data were analyzed through a chi-square test, independent-samples t-test, and logistic regression analysis using SPSS version 22.0. Participants with oral health education experience showed higher levels of oral health knowledge and practice behaviors than those who did not, and the odds of them having oral health care self-efficacy was 3.743 higher. Moreover, a one-unit increase in oral health knowledge and practice behaviors was associated with a 1.199 and 1.351 increase in oral health care self-efficacy, respectively. For oral health promotion among college students, oral health care self-efficacy reinforcement programs tailored to college students should be developed. These should focus on expanding oral health education opportunities to promote improvement in oral health care self-efficacy by strengthening oral health knowledge and the motivation to practice oral health behaviors.

Recent studies highlight the need to introduce objectives in Initial Teaching Education focused on the development of oral language competence (OLC). The main aim of the study is to examine activities to promote the development of OLC that are carried out in university classrooms and their evaluation, to analyze the relationship between students’ awareness of OLC work and class activities and to identify proposals to improve students’ OLC. Participants were 175 university teachers who teach on the bachelor’s degree in Initial Teacher Education (ITE) and the master’s degree in Secondary Education (MSE) at seven Catalan universities. The data collection instrument was an online questionnaire with 69 questions. The results indicate that 92.5% of participants work on OLC in their subjects, that 76.5% propose activities that are specifically linked to OLC and that 65.1% of participants evaluate OLC in their subject. A total of 39.4% of participants reported the need to increase discussions to generate processes of collaborative and interdisciplinary reflection between university teachers from different areas of knowledge, among others. We conclude that professional development processes need to be designed for ITE teachers to reflect on how they help students to develop OLC from a pragmatic perspective.

This scoping review aims to identify the available evidence concerning the clinical and psychosocial impacts of the communication of oral potentially malignant disorders (OPMDs), and to map and analyze knowledge gaps regarding truth-telling about risk factors, malignant transformation, treatment, and follow-up approaches. Search strategy was performed using electronic databases (Medline/PubMed, Scopus, Embase, and Web of Science) and one grey literature database (Google Scholar). Studies focused on communicating the diagnosis of OPMDs and the patients' perceptions were included. Study selection and data extraction were performed by two authors in a two-phase process. Five publications were included in the qualitative analysis. Each publication involved a different study design, study population, types of OPMDs, and results on the important aspects of the professional-patient communication about the diagnosis of OPMDs. Although specific protocols on OPMDs communication have not yet been reported, there is an elevated interest on this topic since the strategies and skills on professional communication could provide better clinical outcomes to the patients. A list of recommendation strategies on how to communicate an OPMD diagnosis is proposed; however, future studies are still needed to design specific communication protocols for OPMD.

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p &lt; 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

In this perspective review, we describe a brief background on the status quo of diabetes mellitus related therapies and glycemic control among patients in rural communities of sub Saharan Africa. We specifically talk about insulin therapy and the challenges of access to insulin and oral hypoglycemic therapies among the diabetic patients living in sub-Saharan Africa. We crown up our discussion with suggestions on solutions and opportunities for future research to tackle this health challenge in these impoverished communities. Our ideas have been informed by the following inquiries: What is the current situation with diabetes in Sub-Saharan Africa? How well controlled are blood sugar levels among diabetes individuals in Sub-Saharan Africa? What is insulin therapy, and for which patient populations is it recommended? What proportions of diabetic patients are on insulin therapy and oral hypoglycemic drugs in Sub-Saharan Africa? Which is the most common therapy given to diabetic patients in the rural communities of sub Saharan Africa between insulin and oral hypoglycemic drugs? Who determines the choice of therapy between insulin and oral hypoglycemic drugs? How often is hypoglycemia and hyperglycemia encountered among people on insulin therapy? Is monitoring glucagon levels important for treating diabetic individuals receiving insulin? Is it normal practice to check the glucagon levels of diabetes patients in sub-Saharan African rural communities? What insulin therapy research has been done in the rural communities of sub Saharan Africa and what research gaps exist in this field? Addressing these research gaps is critical for improving insulin therapy in rural communities of sub-Saharan Africa and reducing the burden of diabetes in these populations.

Background. Oral anticoagulants (OACs) reduce stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) but increase the risk of major bleeding (MB). No study has addressed the incidence and outcomes of bleeding in AF patients in the Middle East (ME). The Jordan AF study evaluated clinical profiles and one-year outcomes of AF patients who sustained bleeding events. Methods. Patients in 29 hospitals and clinics (May 2019 - December 2020) were enrolled and followed up for one year. Demographics and one-year events were compared in patients with or without bleeding. Results. Of 2018 patients enrolled; 166 patients sustained MB or clinically relevant non-major (CRNM) bleeding (8.2 events per 100 patient-years), including 47 patients who had MB (2.3 events per 100 patient-years). Compared with 1852 (91.8%) patients who did not have bleeding, patients with MB were older and had a higher prevalence of hypertension, diabetes mellitus (DM), heart failure, and malignancy, More patients with MB than those with no bleeding were using OACs (93.6% vs. 78.9%, p=0.02). Patients with MB had significantly higher one-year rates of stroke/SE (23.4% vs. 3.6%, p<0.0001) and all-cause mortality (31.9% vs 11.6%, p=0.001). Independent predictors of MB were stroke/SE (OR 10.8, 95% CI 5.3-21.9, p<0.0001), malignancy (3.4, 1.3-8.5, p=0.01), use of OACs (4.4, 1.3-14.7, p=0.02) and DM (1.9, 1.0-3.5, p=0.04). Conclusions. MB and CRNM bleeding occurred in (≈8%) of patients with AF at one year. Patients with MB (≈2%) had worse baseline clinical profiles and one-year prognosis compared with those who did not have bleeding. Keywords: Atrial fibrillation; Major bleeding events; Clinically-relevant non-major bleeding; Oral anticoagulants; Middle Eastern population; Prognosis. Clinical studies registration: the study is registered on clinicaltrials.gov (unique identifier number NCT03917992).

Oral diseases remain a major health problem worldwide, with the World Health Organisation reporting that oral health neglect affects almost half of the world’s population. Quorum sensing molecules (QSMs) influence oral biofilms in various ways with knowledge of direct oral QSM-host interaction being limited, and such studies could provide more insight into the cross-kingdom communication occurring during oral disease development. This review aims to explore the literature on oral QSM-host interaction and to highlight areas of advancement in this field. QSM CSP-1 produced by Gram-positive oral bacteria was found to interact with T2R receptors, activating NF-kB signalling and leading to remodeling of the cytoskeleton. AI-2 in the oral cavity was found in various studies to elicit an inflammatory response in specific oral cells. Overall AHL detection methods remain an area for development, through which greater understanding of oral QSMs’ influence on host cells can be achieved. In conclusion, from the current literature it can be inferred that that QSMs are utilised by host cells to detect bacterial presence and in the majority of cases elicit an immune response towards the environmental QSMs. This may provide a base to target QSMs as novel treatment of oral diseases.

Megalin (LRP2) is a rapidly recycling multiligand endocytic receptor, primarily expressed in polarized epithelial cells. Despite megalin could promote tumor growth and invasiveness through several mechanisms, it has been understudied in the field of molecular oncology so far. The present study aimed to evaluate the impact of megalin expression in oral squamous cell carcinoma (OSCC) on disease progression. Megalin expression was evaluated immunohistochemically in 63 OSCC specimens. Data obtained were retrospectively compared with patients’ clinicopathological features and survival. The proportion of megalin-expressing cells in primary OSCC tissue was significantly associated with metastatic spreading to lymph nodes, vascular invasion and lower overall survival rate. Results obtained by the study suggest that megalin can be considered as a novel molecule involved in OSCC pathogenesis, but also useful as a potential biomarker for cancer progression.

Oral mucosa is a key player in the cancer patient and during cancer treatment. The increasing prevalence of cancer and cancer therapy associated side effects are behind the major role that oral mucosa plays in the oncological patient. Oral mucositis is a debilitating severe complication caused by early toxicity of chemo and/or radiotherapy that can restrict treatment outcome possibilities, even challenging patient’s survival. It has been referred to as the most feared cancer treatment complication. Predictive variables as to who and to what extent will be affected are still unclear. Additionally, oral mucositis is one of the sources of the increasing economic burden of cancer, not only for patients and their families but also for institutions and governments. All efforts should be implemented in the search for new approaches to minimize the apparently ineluctable outburst of oral mucositis along the cancer treatment. New perspectives derived from different approaches in explaining the interrelation between oral mucositis and oral microbiome or the similarities with genitourinary mucosa may help elucidate the biomolecular pathways and mechanisms behind oral mucosa cancer-therapy related toxicity and what is more important its management in order to minimize treatment side effects and to provide enhanced cancer support.

: An innovative and stable probiotics-containing mucoadhesive gel (AL0020), integrated with botanical extracts, has been developed to rebalance the dysbiosis associated with periodontal diseases. Tau-Marin gel was tested against some pathogenic bacteria, belonging to the so-called "red complex", recognized as the most important pathogens in plaque specimens, adherent to the epithelial lining of periodontal pockets. A detailed physico-chemical profile of AL0020 and its in vitro efficacy in protecting activity against pathogenic bacteria as well as soothing or irritative effect on gingival epithelium were reported. Moreover, a clinical-dermatological trial on 20 volunteers using the product once a day for 30 days was also performed.

Evidence regarding the role of oral antibiotics (oA) alone or combined with mechanical bowel preparation (MoABP) for elective colorectal surgery remains controversial. A prospective database of 8,359 colorectal resections gathered over a 32-month period in 78 Italian surgical units (the iCral 2 and 3 studies), reporting patient-, disease-, and procedure-related variables together with 60-day adverse events, was re-analyzed to identify a subgroup of 1,013 cases (12.1%) that received either oA or MoABP. This dataset was analyzed using a 1:1 propensity score-matching model including 20 covariates. Two well-balanced groups of 243 patients each were obtained: group A (oA), and group B (MoABP). The primary endpoints were anastomotic leakage (AL) and surgical site infections (SSIs) rates. Group A vs. group B showed a significantly higher AL risk [14 (5.8%) vs 6 (2.5%) events; OR 3.77; 95%CI 1.22-11.67; p = .021], while no significant difference was recorded between the two groups regarding SSIs. These results strongly support the use of MoABP for elective colorectal resections.

Printed oral splints are a therapeutic alternative in the treatment of functional disorders. Their mechanical properties are crucial to their clinical success and their performance can vary depending on cleaning, post-polymerization, or build orientation. This in vitro study aimed to compare the biaxial flexural strength of the chosen materials depending on the aforementioned parameters. 720 discs (n = 15 per group, 16 mm x 2 mm) were printed from splint materials. Printing was performed under 90°, 45°, or 0° orientation to the building platform with supporting structures. Specimens were either automatically or manually cleaned with isopropanol. Post-polymerization was performed with LED- or Xenon-light. Biaxial flexural strength (BFS) was determined with a piston-on-3-ball test after 24 hours or 60 days water storage (37°C). Test specimens were preloaded with 0.5 N and the load was applied by a piston of 1.6 mm in diameter at 1 mm/min crosshead speed. Statistics were performed by using descriptive statistics, ANOVA, and Levene-tests. Mean BFS after 24 hours of storage varied between 79 MPa and 157 MPa. After 60 hours the BFS significantly decreased and revealed values ranging from 72-127 MPa (mean24 113 MPa, mean60 97 MPa; p&lt;0.001). No significant differences could be determined between the materials (p=0.103) or between the different cleaning procedures (p=0.321). Post-polymerization yielded higher means with LED- (P1: 115 MPa) than with Xenon-light (P2: 95 MPa; p&lt;0.001). Regarding position, the mean values ranged from 101 MPa for 0°, 102 MPa for 45°, and 115 MPa for 90°, which was significantly different (p&lt;0.001). Build orientation of 90° and post-polymerization with LED-light provided significantly higher biaxial flexural strength and should be used to guarantee optimal strength of splint materials. Aging decreased the biaxial flexural strength of the tested specimens.

The influence of preoperative examination of oral squamous cell carcinoma (OSCC) mucosal surrounding by VELscope (Visually Enhanced Lesion Scope) on the radicality of surgical treatment of OSCC was the goal of this study.It is the first analysis of its kind with a total number of 122 patients suffering from OSCC with homogenous distribution of different tumor stages randomized into a study and a control group and enrolled in our study after meeting the inclusion criteria. The preoperative checkup by VELscope accompanied by the marking of the range of a loss of fluorescence in the study group was performed before the surgery. We have developed a unique mucosal tattoo marking technique for this purpose. The pathohistological results after surgical treatment, i.e. the margin status, were then compared. We achieved the pathological free margin (pFM) in 55 patients, the pathological close margin (pCM) in 6 cases and we encountered no case of the pathological positive margin (pPM) in the mucosal layer in the study group. In comparison, the control group results revealed pPM in 7 cases, pCM in 14 cases and pFM in 40 of all cases in the mucosal layer. This study proved that the preoperative autofluorescence evaluation of a tumor mucosal surrounding can enhance the ability to reach the pFM resection.

Microbiological control of dental pathologies presents a significant clinical challenge for dental surgeons, particularly considering drug-resistant microorganisms. To address this issue, Antimi-crobial Photodynamic Therapy (PDT) has emerged as an effective and complementary technique for microbial reduction. This therapy involves the application of a photosensitizer dye (PS) either topically or systemically, followed by exposure to low-power lasers with appropriate visible light wavelengths. PDT has found a valuable place in dentistry across various specialties, including surgery, periodontics, endodontics, dentistry, implantology, orthodontics, and pediatrics. In the realm of pediatric dentistry, managing microorganisms during dental treatments has become a major challenge.This article reviews the evidence supporting the potential of photodynamic therapy in combating bacteria, fungi, and viruses, with a particular focus on areas such as endodontics, restoration in deciduous teeth, implantology, and periodontics for bacterial control. Additionally, PDT has shown promise in stomatology, specifically in the treatment of mucositis and herpes. Considering its promising results and ease of application, photodynamic therapy presents an in-teresting alternative for clinical practice. However, it is important to note that specific protocols must be followed for each application, encompassing the type of photosensitizer, concentration, pre-irradiation time, light type, wavelength, energy, power, and mode of light delivery. Researchers have been steadily refining these protocols to facilitate PDT's integration into clinical practice.

CD44 is known as a cancer stem cell marker of head and neck squamous cell carcinoma (HNSCC) and plays a critical role in cancer malignant progression. Splicing variant isoforms of CD44 (CD44v) are overexpressed in cancers and considered a promising target for cancer therapy. Several monoclonal antibodies (mAbs) against CD44 have been developed by immunizing mice with CD44v3–10-overexpressed cancer cells. In this study, we characterized a novel clone, C₄₄Mab-18 (IgM, kappa). C₄₄Mab-18 reacted with CHO/CD44v3–10, but not with CHO/CD44s by flow cytometry. Enzyme-linked immunosorbent assay revealed that the epitope of C₄₄Mab-18 is determined to be the border sequence between variant 10 and the constant exon 16-encoded sequence. Flow cytometry showed that C₄₄Mab-18 recognizes HSC-3, an oral squamous cell carcinoma(OSCC) cell line. The apparent dissociation constant (K_D) of C₄₄Mab-18 for CHO/CD44v3–10 and HSC-3 was determined to be 1.6 × 10⁻⁷ M and 1.7 × 10⁻⁷ M, respectively. C₄₄Mab-18 detected CD44v3–10, but not CHO/CD44s in western blotting. Furthermore, C₄₄Mab-18 detected endogenous CD44v10 in immunohistochemistry using OSCC tissues. Taken together, C₄₄Mab-18 is useful for detecting CD44v10 in flow cytometry and immunohistochemistry.

FMD is a highly contagious animal disease that occurs in cloven-hoofed animals including pigs. To prevent FMD, vaccines and adjuvants are used to induce an immune response, but it is not sufficient to show the effect of preventing viral infection. In this study, we conducted to evaluate the increasing effect of FMD vaccine SP antibody by administrating Zn-ASP to 100 pigs from three test pig farms with feed. FMD vaccine antibody titer and immunological index were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, and hematological and blood biochemical parameters were analyzed using an automatic blood analyzer. The titer of FMD vaccine SP antibody in the 0.2% Zn-ASP-administered group significantly increased compared to that in the positive control group only injected with FMD vaccine at 4 weeks after the first vaccination and at 4, 8 and 16 weeks after the second vaccination, respectively (p&lt;0.05). The FMD vaccine SP antibody positive rate was 100% until shipment. IFN-γ and IgA were significantly increased by Zn-ASP administration 4 weeks after the first vaccination and 4 weeks after the second vaccination (p&lt;0.05). On the other hand, serum AST, and CPK (p&lt;0.001) were significantly decreased by Zn-ASP. Our results show that the administration of Zn-ASP is effective in enhancing the antibody titer and immunity of the FMD vaccine by FMD vaccination, and it is thought that it can be used as an oral adjuvant (OrAd) to prevent viral diseases such as FMD.

The carriage of Candida albicans in children's oral cavities is associated with a higher risk for early childhood caries, so controlling this fungus in early life is essential for preventing caries. In a prospective cohort of 41 mothers and their children from 0-2 years of age, this study addressed 4 main objectives: 1) Evaluate in vitro the antifungal agent susceptibility of oral Candida isolates from the mother-child cohort, 2) Compare Candida susceptibility between isolates from the mothers and children; 3) Assess longitudinal changes in the susceptibility of the isolates collected between 0-2 years; and 4) Detect mutations in C. albicans antifungal resistance genes. Susceptibility to antifungal medications was tested by in vitro broth microdilution and expressed as minimal inhibitory concentration (MIC). C. albicans clinical isolates were sequenced by whole genome sequencing, and the genes related to antifungal resistance, ERG3, ERG11, CDR1, CDR2, MDR1, and FKS1, were assessed. Four Candida spp (n=126) were isolated: C. albicans, C. parapsilosis, C. dubliniensis, and C. lusitaniae. Caspofungin was the most active drug for oral Candida, followed by fluconazole and nystatin. Two missense mutations in the CDR2 gene were shared among C. albicans isolates resistant to nystatin. Most of the children’s C. albicans isolates had MIC values similar to those from their mothers, and 70% remained stable to antifungal medications from 0-2 years. For caspofungin, 29% of the children’s isolates showed an increase in MIC values from 0-2 years. Results of the longitudinal cohort indicated that clinically used oral nystatin was ineffective in reducing the carriage of C. albicans in children; novel antifungal regimens in infants are needed for better oral yeast control.

Background and Objectives: Trichomonas tenax is a protozoan, participating in the human oral microflora. It is considered as a potential paradontopathogen. This microorganism is also reported in the respiratory tract. We aimed to analyze the available literature about the prevalence of Trichomonas tenax in the population affected by periodontal disease. Materials and Methods: Тhe searching with keywords: ,,Trichomonas tenax” and “periodontal diseases’’ in Scopus, PubMed and ScienceDirect databases was able to identify several systematic reviews and original articles until July 2023. All studies with suffering from periodontal disease people, mentioned year of publication, country, specified detection methods, total number of tested samples as well as the percentage of those infected with Trichomonas tenax were included. Irrelevant articles were excluded. Results: We found 137 studies, but only 64 studies about distribution of Trichomonas tenax in patients with gum disease underwent qualitative analysis. The highest number of studies have been conducted in Iran, Poland and Iraq. Different methods have been used to detect the unicellular organism, each with different specificity and sensitivity. Conclusions: Interest in Trichomonas tenax has grown considerably since 2000. Because of its association with periodontal disease, Trichomonas tenax role in the inflammatory process shouldn’t be overlooked.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent human malignancies and a global health concern with a poor prognosis despite therapeutic advances, highlighting the need for a better understanding of its molecular background. The genomic landscape of OSCC is well-established and recent research has focused on miRNAs, which regulate gene expression and may be useful as non-invasive biomarkers. A plethora of findings regarding miRNA expression have been generated, posing challenges for their interpretation and identification of disease-specific molecules. Hence, we opted to identify the most important miRNA molecules by bridging genetics and epigenetics, focusing on the key genes implicated in OSCC development. Based on published reports, we have developed a custom panel of 15 major oncogenes and a second panel of 5 major tumor suppressor genes. Following a miRNA/target interaction analysis and a comprehensive study of the literature, we selected the miRNA molecules, which target the majority of each gene panel and are reported to be downregulated or upregulated in OSCC, respectively. As a result, miR-34a-5p, miR-155-5p, miR-124-3p, miR-1-3p and miR-16-5p appeared to be the most OSCC-specific. Their expressional patterns, their verified targets and the signaling pathways affected by their dysregulation in OSCC, are thoroughly discussed in this review.

Introduction: Due to the great development of digital technology, through CAD (Computer - Aided Design) and CAM (Computer - Aided Manufacturing) systems, digital models could be used in orthodontic treatment planning decision-making, as there are numerous studies in the literature that support the validity of measurements of digital models of anterior teeth and the total coefficient of Bolton analysis. The aim of the study was to compare the average length value of the current upper and lower arches with that of a hypothetical nickel-titanium wire and the accuracy of the Bolton index measurement. In the present study, 138 dental casts were analyzed using Ortho3Shape software. Using the Ortho3Shape software, it was possible to measure the real and ideal lower arch lengths and, with regard to Bolton analysis, the values of the anterior and total Bolton coefficients. By comparing the values obtained with those of the study by A. Anand Kumar et al. using CBCT and plaster casts, the reliability of the measurements obtained with such CAD/CAM orthodontic software was evaluated. Considering the validity of digital measurements demonstrated by the studies and systematic reviews in the literature, it can be stated that CAD/CAM digital models can be a viable alternative to plaster models in the coming years, as they can facilitate model preservation and retrieval. For future studies and research, it would be preferable to use intra-oral scanners (IOS) in order to ensure greater accuracy, requiring only one step and ensuring a better outcome for the patient.

Background: Cancer patients require cross-professional care during the diagnosis and treatment periods. Therefore, methods for effectively carrying out case management are essential to tumor care. Purpose: To investigate the effects of using the community software LINE Official Ac-count on oral cancer case management. Methods: An experimental design was used; 100 patients were randomly divided into two groups by using a computer-generated random number table. The experimental group used LINE Official Account, which gave them self-care information, timely messages, and one-on-one health-care consultations. The control group followed standard healthcare practices. Results: The experimental group was satisfied with the self-care information provided by LINE Official Account (86.9%), patients regularly checked the self-care information (89.4%) and would check the information when receiving a push notification (54.3%). Ten patients used the one-on-one consultation(20.0%). LINE Official Account had a significant effect on the rate of participation in support groups. Generalized estimating equations indicated a significant difference between the two groups regarding the overall quality of life over 7 days (P = 0.023). Conclusion: Community software applications used in oncological case management can improve self-management and empower, also enable tracking of long-term follow-up effectiveness and reinforce the case manager’s role as a family therapist. Therefore, this study recommends that case manager systems be incorporated into mobile applications to increase the sustainable management, accessibility, effectiveness, and satisfaction of oncological management systems. This study also provides the value of Sustainable Development Goals (SDGs) with Good Health and Well-being, and decreased social withdrawal among patients with oral cancer.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with cancer. Indeed, cancer patients have a significantly higher incidence of AF than that observed in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF as a marker for occult cancer screening, especially in older adults. The pathophysiological mechanisms are many and varied, including the underlying pro-inflammatory state, specific treatments (chemo and radiotherapy) and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general population; however, the numerous interactions with chemotherapeutics, which lead to a significant increase in side effects, as well as the extreme fragility of the patient should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on mechanisms linking AF to cancer patients with a particular focus on therapeutic challenges in this population.

The purpose of the study was to evaluate the success of procedural conscious sedation, using inhaled equimolar nitrous oxide-oxygen (NOIS – EMONO), in patients undergoing routine dental and oral surgery procedures in a Swiss university hospital setting. Materials and methods: The authors conducted a retrospective cohort study of patients that underwent NOIS-supported procedures between 2018 and 2022 at the oral surgery department of the University Hospital of Geneva (HUG), Switzerland. The primary outcome was the measurement of the procedure success and efficacy as defined by the European Society of Anesthesiology. Secondary objectives included the analysis of the types of treatments performed, their indications, patient behavior, and the patient - clinician satisfaction score. Results: 55 patients were included in the study, 85% underwent surgical procedures, the remaining 15% underwent restorative and preventive procedures. The overall treatment success rate was 98.2%, and 97.9% for surgically treated patients. 62% of patients appeared relaxed, calm, and serene, while 16% expressed pain or fear during the procedure. Infiltrative administration of local anesthesia caused stress in 22% of patients, this was significantly lower in sub cohorts who received local topical anesthetics (0%) or a combination of systemic and local topical analgesics (7%). Patients (75%) and clinicians (91%) were satisfied with the procedure. Conclusion: Inhaled equimolar nitrous oxide-oxygen procedural sedation used during dental procedures and oral surgery results in high treatment success and satisfaction rates. The administration of additional topical anesthetics helps reduce the anxiety and stress related to infiltrative anesthesia. Further dedicated studies and prospective trials are needed to confirm these findings.

Food production is a complex matter, affecting people’s lives, organizations’ profits, and the well-being of the whole planet and has multifaceted ethical considerations surrounding its production, distribution, and consumption. This paper addresses the pressing need to confront ethical challenges within the food system, encompassing issues such as environmental sustainability, food security, and individual food choices for better oral and systemic health of all individuals around the globe. From agricultural practices to global trade and food waste, ethical implications are addressed across various domains, highlighting the interconnectedness of ethical decision-making in the food industry. Central themes explored include the ethical dimensions of food production methods, the impact of global trade on food ethics, and the role of individuals in making ethically informed food choices. Additionally, the paper dives into the spiritual and physical significance of food, particularly through the lens of oral health as a gateway to holistic well-being. Recognizing the complexity of the food ecosystem, the paper calls for serious interventions in legislation and economics to promote ethical protocols and techniques for sustainability reasons. It emphasizes the importance of ethical considerations in food safety management systems, regulatory frameworks, and quality standards. Moreover, the paper underscores the need for a comprehensive approach to address ethical dilemmas and moral values inherent in the food industry and oral health policies, advocating for the adoption of the precautionary principle and ethical decision-making frameworks. The article aims to serve as a call to action for stakeholders across the food industry and the healthcare sector, to prioritize ethical practices, promote transparency, rearrange economic parameters and work towards a more sustainable and equitable food system for inner and outer oral and systemic health and human sustainability for all.

The aim of our study was to assess the relationship between the concentration/activity of salivary stress biomarkers (cortisol, α-amylase) and the psychological profile of patients with oral lichen planus (OLP) and primary burning mouth syndrome (BMS). A total of 160 subjects participated in this cross-sectional study: 60 patients with OLP; 60 patients with primary BMS; 40 control subjects. Unstimulated whole saliva (UWS) was collected between 9 and 10 am. Salivary biomarkers were analyzed by enzyme-linked immunosorbent assay (ELISA). Psychological assessment was evaluated with the Depression, Anxiety, and Stress Scale (DASS-21). Patients with primary BMS had higher salivary cortisol concentrations and α-amylase activity (0.52 vs. 0.44 µg/dl; 160531 vs. 145804 U/L) compared with patients with OLP. Patients with primary BMS had statistically significantly higher scores for depression, anxiety, and stress compared with patients with OLP and control subjects (p <0.001, Kruskal-Wallis test). There was a strong positive correlation between anxiety and depression, stress and depression, stress and anxiety in patients with OLP and BMS (p <0.001 and p <0.001, respectively). There was a good positive correlation between symptom intensity (pain/burning) and psychological profile (depression, anxiety, stress) in patients with primary BMS (r=0.373, p=0.003; r=0.515, p <0.001; r=0.365, p= 0.004, respectively). Patients with BMS show a stronger association with mental disorders compared to patients with OLP. However, an interdisciplinary psychoneuroimmunological approach is equally important in both patient groups (OLP and BMS), regardless of whether mental disorders are the cause or the consequence.

Oral squamous cell carcinoma (OSCC) remains an under-studied and significant global cancer killer and dismal survival rates have not changed in decades. A better understanding of the molecular basis of OSCC progression and metastasis is needed to develop new approaches for treating this disease. The supportive network surrounding cancer tumor cells known as the tumor microenvironment (TME) has gained increasing interest lately since it performs essential pro-tumorigenic functions. Cancer-associated fibroblasts (CAFs) are one of the main cell types in the TME and are known to play a key role in influencing the biological behavior of tumors. CAFs present a heterogeneity both in phenotype as well as functions, leading to the suggestion of different CAF subtypes in several cancer forms. The task to subtype CAFs in OSCC has however just begun and there is today no united way of subtyping CAFs in this disease. This review aims to define the features of CAFs and to summarize CAF subtype research in OSCC including aspects as disease prognosis and therapeutic opportunities.

Resveratrol is currently considered an option for chemoprevention and treatment of oral cancer, but the instability and unfavorable pharmacokinetics hinder its use in clinical practice. The present study deals with the preparation of resveratrol liposomes by a method that preserves stability and provides payload high enough for chemoprevention and/or treatment of oral cancer. Different temperatures, RSV concentrations and molar fractions, as well as the presence or absence of vitamin C in the hydration media were assayed. Liposome hydrodynamic diameter, polydispersity and zeta potential were evaluated by dynamic light scattering. In vitro biocompatibility, antioxidant activity and permeability were evaluated using TR146 cells and PermeaPad® membranes. Liposomes were included in hydrogels and films, and their suitability for buccal application was evaluated. According to the results, a temperature of 37ºC was optima to efficiently produce the resveratrol liposomes. Vitamin C was found to influence the liposome size, while resveratrol concentration significantly influenced the entrapment efficiency. High cell biocompatibility and potent intracellular antioxidant activity were observed and the inclusion of vitamin C reinforced the antioxidant effects. High permeation across PermeaPad® membranes and efficient uptake by TR146 cells was proved for resveratrol loaded liposomes. Liposomal hydrogels and films appropriated for buccal application were obtained and the payload of the formulations was high enough to produce mucosa concentrations above resveratrol IC50 values reported for cancer cells.

Dentifrice performance in the removal of dental plaque is influenced by the interactions of dentifrice components with tooth surfaces. This randomized controlled clinical study assessed the effectiveness and safety of a novel fluoride dentifrice formulation that included a micro-fibrillated cellulose network with entangled microcrystalline cellulose and silica particles (ProtegeraTM), and compared this to a positive control fluoride dentifrice (Crest Cavity Protection™). Whole mouth dental plaque levels in 82 healthy adults were measured after the first supervised use, and following a week of twice daily use at home. Overall, the novel dentifrice was at least three times more effective in whole mouth plaque reductions than the reference dentifrice (p < 0.001), with a 38.6% reduction on first use, a 30.9% reduction at day 7, and a 41.6% reduction from day 1 to day 7, compared to reductions of 12.0%, 9.6%, and 11.6% respectively for the positive control. No safety issues arose from the use of the novel dentifrice. These results indicate that including micro-fibrillated cellulose enhances plaque removal effectiveness, without causing adverse changes to oral soft tissues.

Total bilateral Limbal Stem Cells Deficiency is a pathologic condition of the ocular surface due to the loss of corneal stem cells. Cultivated Oral Mucosa Epithelial Transplantation (COMET) is the only autologous successful treatment for this pathology in clinical application, although non-physiological peripheric corneal vascularization often occurs. Properly characterizing the regenerated ocular surface is needed for a reliable follow-up. So far, the univocal identification of transplanted oral mucosa had been challenging. Previously proposed markers were shown co-expressed by the different ocular surface epithelia in a homeostatic or perturbated environment. In this study, we compared the transcriptome profile of human oral mucosa, limbal and conjunctival cells, identifying PITX2 as a new marker that univocally distinguishes the transplanted oral tissue from the other epithelia. We validated PITX2 at RNA and protein levels to investigate 10-year follow-up cor-neal samples derived from a COMET-treated aniridic patient. Moreover, we found novel angiogenesis-related factors differentially expressed in the three epithelia and instrumental in explaining the neovascularization in COMET-treated patients. These results will support the follow-up analysis of patients transplanted with oral mucosa and provide new tools to understand the regeneration mechanism of the transplanted cornea.

Background: The oral health-related quality of life (OHRQoL) assessment evaluated the impact of individual’s oral health on the patient's physical and psychosocial status. We evaluated the association between subjective OHRQoL, measured with the Oral Health Impact Profile-14 (OHIP-14) questionnaire, and unfavorable body mass index (BMI) (i.e., too high or too low) in a large population-based study on older adults from Southern Italy. Moreover, we assessed which of the seven OHIP-14 domains was most strongly associated with an unfavorable BMI. Methods: We used data on a subpopulation of the Salus in Apulia Study, including 216 older adults. BMI &lt;18.4 kg/m2 and &gt;30 kg/m2 were classified as unfavorable, values between 18.5 and 30 kg/m2 were classified as ideal. Results: Higher OHIP-14 total score increased the risk to have an unfavorable BMI [odds ratio (OR):1.08, 95% confidence interval (CI):1.01-1.15]. In the model adjusted for age, sex, education, hypertension, carbohydrate consumption, and alcohol consumption, this finding was confirmed with higher OHIP-14 total score increasing the risk to have an unfavorable BMI (OR:1.10, 95% CI:1.01-1.22), and higher age linked to a decreased risk to have an unfavorable BMI (OR:0.89, 95% CI:0.82-0.97). In a random forest regression model, the most important predictive domains/sub-scales of OHIP-14 in mean decrease Gini for unfavorable BMI were, in order of decreasing importance, physical pain, functional limitation, psychological discomfort, physical disability, social disability, psychological disability, and handicap. Conclusions: In older age, negative OHRQoL, particularly linked to the physical pain domain, increased the risk of underweight or overweight and obesity.

Out of a worldwide annual incidence of ~150 million cases for urinary tract infection (UTI), >25% of outpatient prescriptions of oral antimicrobial treatment (OAT) are for cystitis not complicated by sepsis. OAT aids the immune cells infiltrating urothelium to eliminate uropathogens attaching and invading urothelium amidst hyperosmotic urine. This adaptability of uropathogens and the short interval between Penicillin sale and the first antimicrobial resistance (AMR) report suggests that AMR is a 3.8 billion years old evolutionary conserved heritable trait of surviving environmental threats through exponential proliferation of mutant strains selected by Darwinian principle. Therefore, OAT success with minimal AMR can be ensured by antimicrobial stewardship (AMS) following the principle of 5Ds -drug, dose, duration, drug-route, and de-escalation. While convenient to administer, the onset of minimum inhibitory concentration (MIC) for OAT in urine is a window of opportunity for uropathogens to survive the first contact with OAT and the descendant colonies armed with AMR are likely to survive subsequent higher urine OAT levels. Meanwhile, intravesical antimicrobial treatment (IAT) delivers the first strike well above MIC. The root cause analysis of AMR dovetails with the strengths, weaknesses, opportunity, and threat (SWOT) analysis of OAT in this interdisciplinary review.

The frequency of selected polymorphisms, one in each gene coding for proteins with antioxidative properties (CAT, SOD2, GPX1, NQO1) was compared between patients suffering from pain-related temporomandibular disorders (TMDp;n=85) and control subjects (CTR;n=85). According to the Oral Behaviours Checklist score participants were divided into high-frequency parafunction (HFP;n=98) and low-frequency parafunction (LFP;n=72) groups. In addition, we have investigated the association of selected polymorphisms with participants' psychological (anxiety, depression) and psychosomatic (hypervigilance, somatosensory amplification) characteristics. Polymorphisms rs1001179, rs4880, rs1050450, rs689452 were genotyped using the genomic DNA extracted from buccal mucosa swabs and real-time TaqMan genotyping assays. No differences in genotype distribution between TMDp patients and control subjects were found. Still, TMDp patients who were homozygous for minor allele A, related to the GPX1 polymorphism rs1050450 reported significantly more waking-state oral behaviours compared to GA+GG genotype carriers (score: 30 vs. 23, p=0.019). Frequency of genotype AA for rs1050450 polymorphism was higher in HFP compared to LFP participants (14.3% vs. 4.2%, p =0.030). Most important predictors of waking-state oral behaviours were depression, anxiety, AA genotype (rs1050450) and female sex. Explored genetic factors were not found to be significant risk factors for either TMDp or sleep-related oral behaviours. The association of waking-state oral behaviours with selected gene polymorphisms additionally supports previous assumptions that the daytime bruxism is more closely linked to various stress manifestations, which might also be reflected through the variability related to cellular antioxidative activity.

Cellulose nanocrystals (CNCs) are cellulose-derived nanomaterials that can be easily obtained, e.g., from vegetable wastes produced by circular economies. They show promising antimicrobial activity and the absence of side effects and toxicity. This study investigated the ability of CNCs to reduce microbial adherence and biofilm formation using in vitro microbiological models reproducing the oral environment. Microbial adherence by microbial strains of oral interest, Streptococcus mutans and Candida albicans was evaluated on the surfaces of salivary pellicle-coated enamel disks in the presence of different aqueous solutions of CNCs. The antibiofilm activity of the same CNC solutions was tested against S. mutans and an oral microcosm model based on mixed plaque inoculum using a continuous-flow bioreactor. Results showed an excellent anti-adherent activity of the CNCs against the tested strains from the lowest concentration tested (0.032 wt.%). Such activity was significantly higher against S. mutans than C. albicans, suggesting a selective anti-adherent activity against pathogenic strains. At the same time, there was a minimal albeit significant antibiofilm activity (at least 0.5 and 4 wt.% CNC solution for S. mutans and oral microcosm, respectively). This makes CNCs particularly interesting as anticaries agents, encouraging their use in the oral field.

Atrial fibrillation (AF) is a common arrhythmia associated with various risk factors and significant morbidity and mortality. This article presents findings from a study involving 115 patients with permanent AF. The study examined demographics, risk factors, associated pathologies, complications, and anticoagulant therapy. The results showed a slight predominance of AF in males, with the highest incidence in individuals aged 75 and above. Common risk factors included arterial hypertension, dyslipidaemia, diabetes mellitus type 2, and obesity. Comorbidities such as congestive heart failure, mitral valve regurgitation, and pulmonary disorders were prevalent among the patients. Major complications included congestive heart failure, stroke, and myocardial infarction. Thromboembolic and bleeding risk assessment using CHAD2DS2-VASc and HAS-BLED scores demonstrated a high thromboembolic risk in all patients. The majority of patients were receiving novel oral anticoagulants (NOACs) before admission, while NOACs were also the most prescribed antithrombotic therapy at discharge. The study highlights the importance of risk factor management and appropriate anticoagulant therapy in AF patients to reduce complications and improve outcomes.

This study centered on examining 60 different antibiotics by assessing their primary toxicity parameters through the pkCSM database. The parameters included Max. Tolerated Dose (Human) (log mg/kg/day), Oral Rat Acute Toxicity (LD50) (mol/kg), Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day), and Minnow Toxicity (LC50) (log mM). The results highlight four potential antibiotics—cefotaxime, ceftriaxone, imipenem, and meropenem—that exhibited lower toxicity effects compared to other compounds. These findings imply a relatively favorable safety profile for these antibiotics concerning the specified toxicity parameters. However, it is crucial to interpret these outcomes within the context of the specific clinical application and to consider additional factors for a comprehensive safety assessment. It's essential to acknowledge that evaluating toxicity is intricate, and the determination of what is considered "less toxic" can rely on specific criteria and the context of use. Furthermore, individual responses to antibiotics may vary, and the selection of an antibiotic should be based on diverse factors, including the specific infection being treated, the patient's health, and potential side effects.

Dental-implant-supported reconstructions provide comfort and improvements in prosthetic function, adaptation, and stability over conventional treatment options. The objective of this study was to evaluate the effect of multiple cleaning solutions on dentures and their influence on the deterioration and loss of retention of overdenture attachments in a 12-month clinical-use simulation. In this way, four different brands of retentive caps made of Teflon (OT Equator, Locator®, Kerator®, and Locator R-Tx®) were immersed in five different cleaning solutions (Kukident®, Benfix®, Corega®, and Protefix®), and tap water was used as the control group, in a simulation that lasted 12 months. Data were analyzed using two-way ANOVA and a Tukey HSD. Furthermore, a Levene Test and Shapiro–Wilk tests were performed to assess the validation of the ANOVA assumptions. The statistical analysis was performed using R version 4.2.2 software with the significance level set to p &lt; 0.05. There were significant statistical differences between the different manufacturers on the retention forces of the attachment’s retentive caps. For the cleaning solution groups, different statistical results between Kukident® and Benfix® were observed. There were no significant statistical differences between Corega®, Protefix®, and tap water despite the fact that the retention forces decreased in all of them.

Objective: To evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. Methods: multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011-December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. Results: 243 patients were included, ninety-five (44.2%) used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients treated with denosumab without CDK4/6 inhibitors the incidence of MRONJ and mean time to the occurrence of MRONJ was 6.6% (8/120) and 16.8 months (SD 7.8) respectively. In patients treated with denosumab and CDK4/6 inhibitor 13.7% (13/95) and 15.4 month (SD 8.7) respectively. The difference in the incidence was not significant (p=0.085). Conclusion: it suggest that the incidence of MRONJ in patients with metastatic breast cancer treated with denosumab was higher and the onset of MRONJ occurred earlier in the presence of CDK4/6 inhibitors. Although the difference was not significant, given that the use of this combination is very common in routine clinical practice, it would be advisable to carry out larger prospective studies to clarify the risk of this association.

Background - Mandibular flexion (MF) is a complex biomechanical phenomenon, which involves a deformation of the mandible, due mainly to the contraction of the masticatory muscles, and can have numerous clinical effects. The main aim of the current systematic review is to highlight the different factors that can increase MF, to help clinicians, identify patients to whom they should pay more attention. As a secondary outcome, we wanted to analyze the preventive measures and suitable techniques to be adopted to minimize the negative effects of this phenomenon on oral fixed rehabilitations. Methods - The review, which was carried out in accordance with the “Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) flowchart, was recorded in the “International Prospective Register of Systematic Reviews” (PROSPERO). As research questions, “Patient/Population, Intervention, Comparison and Outcomes” (PICO) questions were employed. Using the ROBINS-I technique, the risk of bias in non-randomized clinical studies was evaluated. Results - The initial electronic search identified over 1300 potential articles, of which 54 studies were included in this systematic review. Information regarding the relationship between MF and individual factors, mandibular movements, impression-taking and fixed rehabilitations were obtained. Conclusions – The studies included in this systematic review showed that MF is greater during protrusive movements, in the posterior areas of the lower jaw, and in patients with brachial facial type, greater jaw length, small gonial angle and less density, length and bone surface of the symphysis. The biomechanical effects of mandibular flexion on fixed restorations are debated. Prospective clinical and radiological observational studies should be conducted to evaluate the potential short-, medium- and long-term consequences of MF.

Oral cancer ranks sixth among Taiwan's top 10 cancers, and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. Migration and invasion assays confirmed OSCC cells' EMT capabilities, whereas flow cytometry and Western blotting identified the molecular pathways. ALA dramatically reduced cell growth in a concentration dependent manner, according to the findings. Low concentrations of ALA (100 or 200 μM) inhibit colony formation, expression of Twist and EMT-related proteins, expression of MMP2/-9 proteins and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 μM) greatly increases JNK phosphorylation and c-jun nuclear accumulation, then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins, or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients.

Despite recent advancements, therapies remain ineffective against advanced oral squamous cell carcinoma (OSCC), resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Yet, the exact mechanisms driving CAP-induced cancer cell death are not fully understood. This study revealed a significant reduction in the viability of OSCC cell lines, inactivation of AKT and ERK, and the downregulation of the miR-21, miR-31, miR-134, miR-146a and miR-211 expression followed the CAP treatment. Pretreatment with ZVAD, 3-MA, and Fer-1 synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways by CAP. Activation of AKT and ERK, alongside combined treatments using death inhibitors and miRNA mimics, counteracted the cell mortality associated with CAP. CAP-induced downregulation of miR-21, miR-31, miR-187 and miR-211 expression was rescued by AKT and ERK activation. Additionally, CAP treatments notably inhibited the growth of SAS cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study indicates that CAP jet treatment diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.

Background: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient’s quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ at risk (OAR) avoidance structure, provider and patient reported outcomes (PROs), opioid use, and hospitalization. Methods: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. Results: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p=0.0082) and hospitalization (p=0.0356) during and within 30 days of completing RT. Conclusion: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment.

The current paper presents a case of a 33-year-old female with an uncommon localization of a leiomyoma in the oral cavity - the anterior palatal fibromucosa and the incisive papilla. The patient referred to the Oro-Maxillo-Facial Surgery Clinic of the Emergency City Hospital Timisoara, Romania accusing a slight discomfort in the act of mastication and the occurrence and persistence of a diastema between the upper central incisors, due to the presence of a tumoral mass located in the anterior palatal mucosa, between the upper central incisors, without any changes of the subjacent bone structure in the anterior hard palate visible on the cone beam computed tomography image (CBCT). The tumor was removed by a surgical excisional biopsy and a histopathological examination was performed using morphological Hematoxylin–Eosin (HE) staining and additional immunohistochemical (IHC) reactions, in order to confirm the diagnosis. On microscopic examination, there were found bundles of spindle cells with eosinophilic cytoplasm and vesicular nuclei, with finely granular chromatin. The immunohistochemically staining found positive results for smooth muscle actin (SMA) and desmin and negative result for vimentin. The treatment of choice for leiomyoma of the oral cavity is surgical excision with clear margins, followed by periodical clinical monitoring.

Immediate load of full-arch rehabilitations over implants, specially over 4 implants are very well documented in the literature. More recently, the use of computed surgical guides to help the planning and the execution of these treatments, in many situations without the need of raising a flap, and diminishing the appearance of hematomas, bleeding and with less trauma to the patient has gained preference among implantologists. The objective of this case report is to show a clinical case of an immediate load full-arch fixed rehabilitation over 4 implants produced by 3D printing manufacturing technology, and placed with a computed surgical guide, in the same appointment, and the 24 months follow-up. The patient returned after 3 months to replace the immediate temporary fixed prosthesis for a new one, with metallic bar, better teeth and more delicate. Soft and hard tissue around the implants seemed to be stable, without signs of inflammation, either on the 3 or the 24 months follow-up. 3D printing of implants by direct metal laser sintering is a technology that seems to be promising for oral implantology, with solid studies showing reliable results, as seen in this single case. More clinical studies are necessary to testify its efficacy.

Background and objective: Research shows that 60–90% of school children have caries, representing a serious public health issue. Here, we present a model of oral health promotion that has been conducted in the Primorje-Gorski Kotar County (PGC), Croatia, from 2008 to 2019. We assessed the oral status of first and fifth grade elementary students and determined the sustainability and influence of our model on the status and behavior regarding the children’s oral status. Additionally, during the observed period, promotional and preventative activities aiming to improve oral health were conducted. Since 2014, the Program has begun to be continuously, comprehensively, and systematically introduced into preschools as well. Material and methods: We assessed the number of children with caries by analyzing the changes in the decayed, missing, and filled teeth for primary teeth (dmft)/decayed, missing, and filled teeth for permanent teeth (DMFT) index mean during the observed period. Results: From 2008 to 2019 we assessed 44422 children in the PGC (21714 first grade and 22708 fifth grade students). The average response rate throughout the Program has been 83%. We have noted a dmft/DMFT index decrease from 4,66 to 3,73 (first graders) and from 2,50 to 1,00 (fifth graders). Conclusions: The Program has improved the behavior and oral health of children; stakeholders from various professions have been included, such as health visitors, school medicine teams, and pediatricians, avoiding additional financial expenses, increasing the number of children in care, and proving the sustainability of our oral health improvement model.

Background: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials.gov - NCT02942745) is the first known randomized trial designed for ANBQ chewers. Methods: We compared intensive behavioral treatment intervention condition (IC) with control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n=88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n=88) received only the brochure. Participants were assessed at baseline and day-22 follow-up. Self-reported chewing status at day-22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. Results: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p=0.0058, which met the Stage 3 criteria for significance and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). Conclusion: Robust self-reported intervention effects at day-22 suggests that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in ADL. Fractures in the elderly people are associated with bone fragility. Diabetes and chronic kidney disease are associated with bone fragility. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

Oral ferric citrate hydrate (FCH) is effective for iron deficiency in hemodialysis patients.; however, it remains unclear how iron balance in the body affects iron absorption from the intestinal tract. This prospective, observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406), conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables on ΔFe2h and the secondary outcome was the description of the predictors of body iron balance. Generalized estimating equations (GEE) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and MCH decreased (-0.155, -0.242 to -0.068, p = 0.001; -2.574, -4.421 to -0.726, p = 0.006, respectively) in GEE. Hepcidin-25 increased when erythropoiesis-stimulating agent (ESA) decreased (-0.002, -0.002 to -0.001, p=0.000). FTN increased when RBC and ESA decreased (-0.466, -0.605 to -0.327, p=0.000; -0.002, -0.004 to -0.000, p=0.05, respectively. Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC-iron to FTN-iron, inhibiting iron absorption even with continued FCH intake.

During pregnancy, profound physiological changes occur in the maternal body, including those affecting oral health. Dental stem cells (DSCs) have emerged as promising candidates for regenerative therapies in dentistry. This manuscript delves into the intricate interplay between DSC behavior and maternal oral health during pregnancy. We provide an overview of current knowledge concerning the impact of pregnancy on DSCs, highlighting their potential roles in maintaining oral homeostasis and responding to pathological conditions. Additionally, we identify key research gaps and propose future directions for investigating novel therapeutic strategies leveraging DSCs to improve maternal and fetal oral health outcomes. By elucidating this relationship, we aim to pave the way for innovative approaches in preventive and regenerative dentistry tailored to the unique needs of pregnant women.

Introduction: Oral candidiasis is an opportunistic fungal infection, often caused by Candida albicans. One of the virulence factors of C. albicans is sterol 14a-demethylase or CYP51. Compounds of anthocyanins (ternatin, cyanin) and flavonoids (rutin, isoquercetin, kaempferol, myricetin, limocitrin) from the extract of the Clitoria ternatea (butterfly pea) plant are believed to have potential to inhibit the CYP51 virulence factor of C. albicans to suppress oral candidiasis. The purpose of this research was to investigate the interaction between the ligands of anthocyanins and flavonoids from C. ternatea (butterfly pea) with CYP51. Methods: The in silico study applied molecular docking to examine the molecular interactions (binding affinity) between the anthocyanin and flavonoid ligands of interest from C. ternatea and the CYP51 receptor of C. albicans. Results: Predicted interactions exist between the ligands of anthocyanins (ternatin, cyanin) and flavonoids (rutin, isoquercetin, kaempferol, myricetin, limocitrin) from C. ternatea and the CYP51 receptor of C. albicans. Conclusion: C. ternatea has the potential to provide anti-fungal agents that can inhibit or slow down the occurrence of oral candidiasis, as indicated by in silico studies. However, it is important to conduct additional research regarding the properties of the plant to determine the unknown aspects of its effects to the human body.

Two billion people worldwide suffer from anemia with reproductive-age women being disproportionately affected. Iron plays a crucial role in cellular function and impacts cognition, physical function, and quality of life. Iron deficiency (ID) and iron deficiency anemia (IDA) are associated with adverse effects on pregnancy and fetal development. Oral iron supplementation has been the standard treatment for IDA for decades often producing sub-optimal outcomes. Many babies are still being born with ID and suffer adverse sequelae due to inadequate iron levels in the mothers. Is it time to consider broad scale-up of parenteral iron as a new standard of care?

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in activities of daily living. Fractures in the elderly people are associated with bone fragility, which is influenced by diabetes and chronic kidney disease. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

To increase the prediction accuracy of positive oral food challenge (OFC) outcome during stepwise slow oral immunotherapy (SS-OIT) in children with hen’s egg (HE) allergy, we evaluated the predictive value of the combination of antigen-specific IgE (sIgE) with antigen binding-avidity and sIgG4 values. Sixty-three children with HE allergy undergoing SS-OIT were subjected to repeated OFC with HE. We measured the ovomucoid (OVM)-sIgE by ImmunoCAP or densely carboxylated protein (DCP) microarray, sIgG4 by DCP microarray, and the binding-avidity of OVM-sIgE defined as the level of 1/ IC50 (nM) measured by competitive binding inhibition assays. The OFC was positive in 37 (59%) patients undergoing SS-OIT. Significant differences in DCP-OVM-sIgE, CAP-OVM-sIgE, I/ IC50, DCP-OVM-sIgG4, the multiplication products of DCP-OVM-sIgE and binding-avidity of DCP-OVM-sIgE (DCP-OVM-sIgE/IC50) and DCP-OVM-sIgE/sIgG4 were compared between the negative and positive groups (p<0.01). Among them, the variable with greatest area under the receiver operating characteristic curve was DCP-OVM-sIgE/IC50 (0.84), followed by DCP-OVM-sIgE/sIgG4 (0.81). DCP-OVM-sIgE/IC50 and DCP-OVM-sIgE/sIgG4 are potentially useful markers for the prediction of positive OFC during HE-SS-OIT and may allow proper evaluation of the current allergic status in the healing process during HE-SS-OIT

Caries are lesions caused by acidic compounds derived from the metabolism of bacteria such as streptococci. It is not merely the presence of acidogenic bacteria that causes caries but an imbalance in the oral biofilm microhabitat and its behavior. One factor underlying biofilm formation is quorum sensing (QS), that in gram-positives relies on peptidic molecules, whereas in gram-negatives is driven by small diffusible signals. Strategies based on QS inhibition have been proposed as alter-natives to antimicrobial therapies. Here, we investigate the antibiofilm potential of the lactonase enzyme Aii20J, previously reported as effective against biofilms of periodontal disease origin. We generated in vitro polymicrobial biofilms dominated by gram-positive taxa using supragingival samples from caries-free and caries-active children. The effect of Aii20J on the biofilms was evalu-ated regarding its biomass-reducing ability, as assessed with crystal violet assay, and its effects on the bacterial composition of the polymicrobial biofilms, as assessed by 16S community profiling. We describe significant biomass reductions upon Aii20J exposure without significant changes in bac-terial composition at the genus level. Our results support the use of Aii20J to prevent oral biofilm formation while highlighting the influence of the polymicrobial environment on bacterial commu-nities and their response to antibiofilm treatments.

Aujeszky Disease Virus (ADV) is a double-stranded DNA virus with a lipoprotein envelope. The natural hosts of the infection are suidae, but the virus can infect many other mammals. The gold-standard method identified by the WOAH for the diagnosis of Aujeszky disease is ELISA method. The objective of this study was to compare the performance of meat juice and oral fluid matrices using a commercial ELISA kit designed for serum. A total of 80 blood and oral fluid samples were collected from four pig farms selected for this study. Diaphragm muscle samples of about 100 g and blood samples were collected from 213 animals at the abattoir. These biological matrices were collected from the same animals and tested using a competitive ELISA kit to detect antibodies against ADV. The relative accuracy of the meat juice compared to that of the serum was 96.7% (95% CI: 93.3%-98.7%), with 206 correct results out of 213. The relative accuracy of the oral fluid compared to that of the serum was 61.3% (95% CI: 49.7%-71.9%), with 58 correct results out of 80. Meat juice has a better combination of sensitivity and specificity than oral fluid. The usage of meat juice in routine diagnostic examinations could be achieved after further investigations to optimize the procedure.

The prevalence of allergic diseases, including food allergy, is increasing, especially in developed countries. Implementation of an elimination diet is not a sufficient therapeutic strategy in patients with food allergy, whose quality of life is significantly impaired. In recent years, new effective therapeutic strategies have been developed, such as the application of oral, sublingual, and epicutenous immunotherapy. Oral immunotherapy is the most often applied strategy because of its effectiveness and ease of application, with an acceptable safety profile. The effectiveness of oral immunotherapy in patients with egg, cow's milk and peanut allergy has been proven both in terms of raising of the threshold and the development of tolerance, and in some patients, the development of sustainable unresponsiveness. Although oral immunotherapy is an effective treatment for food allergy, several limitations, including long duration and a significant rate of reported adverse events, reduces its success. Therefore, new therapeutic options, such as treatment with biologicals, either as combinations with food allergen immunotherapy or as monotherapy with the aim of improving the efficacy and safety of treatment are being investigated..

The aim of the study was to analyze the oral etiology of patients with odontogenic sinusitis (ODS）and to compare the differences in demographic data, clinical symptoms, extent of sinus involvement, bone penetration of the maxillary sinus floor (MSF) between different etiologies. A retrospective investigation was conducted on 103 patients with ODS recruited from Beijing Tongren Hospital. All enrolled patients underwent sinus CT, nasal endoscopy, and oral examination. A comparison of the patients' clinical symptoms, extent of involvement of the sinuses, and bone resorption of the MSF according to odontogenic etiologies was conducted. Follow-up was based on symptoms, clinical examination. The most common odontogenic etiologies were endo-periodontal lesions (EPL. 49.5%), apical periodontitis (AP, 32.0%) and periodontitis (PE, 8.7%). There were statistically significant differences in age (P=0.002), sex (P=0.036), inflammation involving the ethmoid sinus (P=0.037), and bone penetration of the MSF (P<0.001) between the AP, EPL, and PE groups. There were no significant differences in sinusitis symptoms (P>0.005) among patients with different odontogenic etiologies. In conclusion, EPL is a neglected oral etiology with a destructive effect on the bone of the MSF, and Should receive more attention in diagnosis and treatment.

The microbiota in the oral cavity has a strict connection to its host. Its unbalance may determine oral diseases and can also have an impact on the systemic health. Probiotic strains may help in the restoration of a balanced condition. For this purpose, we screened the antibacterial and antiadhesive activities of many viable probiotic strains (Lactobacillus acidophilus PBS066, Lactobacillus crispatus LCR030, Lactobacillus gasseri LG050, Lactiplantibacillus plantarum PBS067, Limosilactobacillus reuteri PBS072, Lacticaseibacillus rhamnosus LRH020, Bifidobacterium animalis subsp. lactis BL050, Lacticaseibacillus paracasei LPC 1101, L. paracasei LPC 1082, and L. paracasei LPC 1114) against two main oral pathogens, Streptococcus mutans and Aggregatibacter actinomycetemcomitans, involved in dental caries and periodontal disease development and progression. Our results, obtained through agar overlay assay, plate count method, and scanning electron microscope imaging, indicate that the tested probiotics prevent the growth and adhesion of oral pathogens in a strain-specific manner, improving oral health. L. plantarum PBS067, L. rhamnosus LRH020, L. paracasei LPC 1101, L. paracasei LPC 1082, and L. paracasei LPC 1114 performed in a significant way against both pathogens in all the tests used. They can be considered as an effective adjuvant to guarantee oral and systemic well-being.

Abstract: Background: This research aims to investigate the oral health status and needs of individuals with disabilities, a vulnerable population that is facing barriers in accessing and maintaining oral care. Methods: Data for this study were obtained through self-administered questionnaires distributed to individuals with disabilities who were receiving assistance from Helping Restore Ability and Neuro Assistance Foundation. The data were analyzed using statistical methods using SPSS and Microsoft Excel to identify patterns and associations related to oral health maintenance among individuals with disabilities. Results: The findings of this research indicate a high prevalence of poor oral hygiene, periodontal diseases, and untreated dental caries, risk factors of oral cancer among individuals with disabilities. Social determinants were found to have a significant influence on the oral health status of this population. The study also highlights the crucial role of caregivers in ensuring oral health maintenance. Conclusion: The results of this study underscore the urgent need for targeted interventions and improved caregiver awareness to address the oral health needs of individuals with disabilities. By addressing the disparities and barriers faced by people with disabilities in accessing dental care, we can mitigate the health, social, and economic burdens associated with poor oral health in this vulnerable population.

Human papillomavirus (HPV) is one the most common sexually transmitted infections (STI), spreading through direct sexual contact to oropharynx and anogenital regions. Although most infected individuals may be asymptomatic and naturally undergo viral clearance, in some individuals’ HPV infection causes carcinogenesis of the infected epithelia. HPV now accounts for over 70% of oropharyngeal carcinomas (OPC). Over 90% of these OPC are associated with HPV 16, one of the 14 high-risk subtypes. In recent years, HPV positive (HPV+) OPC has been one of the most rapidly rising cancers, by new cancer incidence rates, especially among men. They present some unique infection driven cellular and molecular features, in comparison to other head and neck carcinomas (HNC), constituting distinct preventive, therapeutic and prognostic strategies - with significant strides made in this area. However, HPV+OPC are routinely detected at a later stage, adding to the disease burden and overall survival. In this review, we provide a summary of HPV from a STI to malignant transformation, while also parsing through the immune response environment. We further collate key literature around infection sites, diagnostics and clinical management, while throwing light on the current state of epidemiology, transmission, screening and prevention strategies. Indeed, our improving understanding of the disease’s molecular biology has added some success to the prognostic outcomes of certain HPV+OPC across clinical trials examining targeted therapeutics and immunotherapy. This work is directed towards improving our current understanding of HPV and associated oncogenic landscape, to guide screening, early detection, triaging and further prevention and management strategies.

Background: Metastatic oral squamous cell carcinoma (OSCC) is associated with poor patient prognosis. Metastasis is a complex process involving various proteins, tumor cell alterations including changes caused by the epithelial-to-mesenchymal transition (EMT) process, and interactions with the tumor microenvironment (TME). In this study, we investigate a combined protein marker system consisting of connexin 43 (Cx43), EMMPRIN (CD147), E-cadherin and vimentin during the invasive metastatic process of OSCC and the possibility of using this system for prognosis prediction. Methods: The protein expression profiles of Cx43, EMMPRIN, E-cadherin and vimentin were investigated by immunohistochemistry in tissue samples from 24 OSCC patients. The metastatic process was mapped through different regions of interest (ROI) of adjacent healthy oral mucosa (OM), center of primary OSCC, invasive front (IF), and local cervical lymph node metastases (LNM). Disease-free survival (DFS) and overall survival (OS) were the primary clinical endpoints. Results: Significant changes in the expression profiles of the different marker proteins were detected between the different ROIs (all p values &lt; 0.05). Multivariable Cox regression analysis revealed a significant effect of increased EMMPRIN expression towards IF on DFS (p = 0.019) and OS (p = 0.023). The combined predictive analysis showed a significant predictive value of the marker system for DFS (p = 0.0017) and OS (p = 0.00044). Conclusions: The combined marker system was able to significantly predict patient prognosis. An increase in EMMPRIN expression towards IF showed the strongest effect and could be an interesting new antimetastatic therapy approach.

The role of desmoglein-3 (DSG3) in oncogenesis is unclear. This study aimed to uncover molecular mechanisms through comparative transcriptome analysis in oral cancer cells, defining potential key genes and associated biological processes related to DSG3 expression. Four mRNA libraries of oral squamous carcinoma H413 cell lines were sequenced and 599 candidate genes exhibited differential expression between DSG3-overexpressing and matched control lines, with 12 genes highly significantly differentially expressed, including 9 upregulated and 3 downregulated. Genes with known implications in cancer, such as MMP-13, KRT84, OLFM4, GJA1, AMOT, and ADAMTS1, were strongly linked to DSG3 overexpression. Gene ontology analysis indicated that the DSG3-associated candidate gene products participated in crucial cellular processes such as junction assembly, focal adhesion, extracellular matrix formation, intermediate filament organization, and keratinocyte differentiation. Validation of RNA-Seq was performed through qRT-PCR, Western blotting, and immunofluorescence analyses. Furthermore, transmission electron microscopy meticulously examined desmosome morphology, revealing slightly immature desmosome structure in DSG3-overexpressing cells compared to controls. No changes in desmosome frequency and diameter were observed between the two conditions. This study underscores intricate and multifaceted alterations associated with DSG3 in oral squamous carcinoma cells, implying a potential oncogenic role of this gene in biological processes that enable cell communication, motility and survival.

Oral Squamous Cell Carcinoma is one among the most common cancer and early detection is the main key to avoid deaths. Automated diagnostic tools that process the histopathological images of a patient to detect abnormal oral lesions will be very much useful for the clinicians. A deep learning framework have been designed with an intermediate layer between feature extraction layers and classification layers for classifying the histopathological images into two categories, namely normal and oral squamous cell carcinoma. The intermediate layer is constructed using the proposed Swarm Intelligence technique called Modified Gorilla Troops Optimizer. Various optimization algorithms are implemented in literature for optimal parameter identification, weights updating and feature selection in deep learning models, but this work focuses on usage of optimization algorithm as intermediate layer that transforms the extracted features into the features that are more suitable for classification. Three datasets totally comprising 2784 normal and 3632 oral squamous cell carcinoma subjects are considered in this work. Three popular CNN architectures namely InceptionV2, MobileNetV3, and EfficientNetB3 are investigated as feature extraction layers. Two fully connected Neural Network layers along with batch normalization and dropout are used as classification layers. Among the investigated feature extraction models, MobileNetV3 performs well in all the three datasets with the highest accuracy of 0.89. Usage of the proposed Modified Gorilla Troops Optimizer as an intermediate layer boosts this accuracy to 0.95.

Despite improved knowledge regarding diagnosis and treatment of osteomyelitis of the jaw (OMJ), it remains a clinical challenge for oral and maxillofacial surgeons. This study aimed to identify risk factors associated with severe forms of OMJ, i.e. related to the occurrence of major complications or the refractory course of the disease. A retrospective study was performed based on the medical records of all patients diagnosed with OMJ from the past 20 years. Collected data included demographic information, medical and dental history, clinical, radiological, and bacterial findings as well as treatment modalities. The main outcome variables were the onset of major complications and treatment results. Fifty-four patients were included. Our results showed that alcohol and smoking habits, as well as malnutrition, were significantly associated with the occurrence of major complications. We also established that dental implant–induced OMJ should be considered as an aggressive subtype of OMJ. Finally, clinical bone exposure was significantly associated with unfavorable outcomes, whereas dental causes or radiological evidence of periosteal reaction were predictive of successful outcomes. Identifying such factors could be useful in preventing serious complication and informing patients about the refractory course of the disease based on the presence of these factors.

This paper presents the case of a 75-year-old female with an extensive lesion located in the hard palate. Intraoral examination revealed an exophytic white lesion that extended from the entire left maxillary alveolar ridge to the palate beyond the midline. A thorough clinical, radiological, and histopathological examination confirmed the diagnosis of oral verrucous carcinoma.

Background: PD1 and its ligand PD-L1 are related to the prognosis in many solid tumors, whether its role in oral squamous cell carcinoma (OSCC) remains unclear. Methods: Retrospective monocentric study including all patients with OSCC diagnosed and treated between 01/2020 and 05/2022. PD-L1 expression was assessed by combined positive score (CPS), considering CPS > or equal to 1 as positive (1-20 “low expression”, and ≥20 “high”). Descriptive analysis of patient cohort and tumors was performed, including tumor size, stage, lymph node involvement, recur-rence and survival. Results: 65 patients (65 tumors) were analyzed. 66.15% of tumors were ad-vanced stages (III-IV), of them, 97.67% PD-L1+ versus 71.42% within early stages (I-II). T4 tumors expressed PD-L1 in 100% of cases, compared with 54’54% in T1 tumors. 50.79 % of tumors showed lymph node involvement (pN+), 100% of them showing PD-L1+. Prevalence of pN+ was 59.38% for PD-L1 high expression versus 40.63% for low expression. Patients' follow-up ranged from 2 to 34.5 months. No significant difference was seen between overall survival (OS) and PD-L1 +/- (CPS ≥1 vs CPS <1) neither PD-L1 high (CPS ≥20) vs low CPS <20) (p 0.97 and 0.64, re-spectively). Conclusions: The method used to measure (laboratory test with Dako 22C3 an-ti-PD-L1 primary antibody) PD-L1 was reliable and accurate, with a correlation coefficient be-tween the PD-L1 expression in the biopsy and surgical piece of 0.83 (p 0.0001). CPS≥1 was ob-served in large tumors (p<0.001), and was correlated with of lymph node metastases (p<0.004). Further analysis of PD-L1 expression and its relevance in tumor biology and prognosis is needed.

Background: Metastatic tumors to the oro-facial tissues are rare, with an incidence ranging between 1% and 8% of all oral malignant tumors. Generally reported with a peak of incidence in the 5th–7th decades, but possibly occurring at any age, metastases may represent the first sign of an occult cancer or manifest in patient with an already known history of a primary carcinoma, mostly from the lungs, kidney, prostate, and colon-rectum in males, or uterus, breast, lung, and ovary in females. In the oro-facial tissues the sites mostly involved are the oral mucosa, gingiva/jawbones, tongue, and the salivary glands. Methods: A systemic Review of the literature on the oro-facial metastases from Renal Cell Carcinoma has been conducted by searching the most used databases, also focusing the attention on the Clear Cell histological variant, representing the most frequent one. Results: Among the 160 analyzed studies, 211 cases of oral metastases of renal cancer were found (148 in males, 70.1%; 63 in females, 29.8%), with an average age of 59.8 years. In almost 40% of cases, metastasis represented the first clinical manifestation of the primary tumor and 122 were histologically diagnosed as ccRCCs (57.8%). The tongue was involved in most of the cases (26% - 55 cases), followed by mandible (18.9% - 40 cases), gingiva (18.4% - 39 cases), maxilla (10.9% - 23 cases), parotid gland (10.4% - 22 cases), buccal mucosa (5.2% - 11 cases), lips (3.3% - 7 cases), hard palate (2.8% - 6 cases), soft palate, masticatory space and submandibular gland (0.9% - 2 cases), lymph nodes, tonsil and oral floor (0.4% - 1 case). Among the 122 ccRCCs (84 were males, 68.8 %; 38 females, 31.1%), with an average age of 60.8 years and representing in 33.6% the first clinical manifestation, the tongue remained the most involved site (25.4% - 31 cases), followed by the gingiva (17.2% - 21 cases), parotid gland (13,1% - 16 cases), mandibular bone (12.2% - 15 cases), maxillary bone (11.4% - 14 cases), buccal mucosa and lips (4.9% - 6 cases), hard palate (4% - 5 cases), submandibular gland and soft palate (1.6% - 2 cases), lymph nodes, tonsil, oral floor and masticatory space (0.8%. 1 case). The clinical presentation in soft tissues was represented by a fast-growing exophytic mass, sometimes accompanied by pain. Instead inn bone appeared as radiolucent lesions, with ill-defined borders and cortical erosion. Conclusions: Our data focus the attention on the incidence of Renal cancer Metastases in the oro-facial tissues. Their early identification surely represents a diagnostic challenge, especially when the clinical work-up is limited to the cervico-facial region. Nevertheless, early diagnosis and recently introduced adjuvant therapies may represent the key for better outcomes. Therefore, general guidelines about clinical and radiological identification of oro-facial potentially malignant lesions should be part of the cultural background of any dentists.

Extracellular vesicles (EVs) are membrane-bound particles released from cells, and their cargo can alter the function of recipient cells. EVs from X-irradiated cells have been shown to play a likely role in non-targeted effects. However, EVs derived from proton irradiated cells have not yet been studied. We aimed to investigate and compare the proteome of EVs and their cell of origin after proton or X-irradiation. The EVs were derived from a human oral squamous cell carcinoma (OSCC) cell line exposed to 0, 4, or 8 Gy with either protons or X-rays. The EVs and irradiated OSCC cells underwent liquid chromatography-mass spectrometry for protein identification. Interestingly, we found different protein profiles both in the EVs and in the OSCC cells after proton irradiation compared to X-irradiation. In the EVs, we found that protons cause a downregulation of proteins involved in cell growth and DNA damage response compared to X-rays. In the OSCC cells, proton and X-irradiation induced dissimilar cell death pathways and distinct DNA damage repair systems. These results are of potential importance for understanding how non-targeted effects in normal tissue can be limited and for future implementation of proton therapy in the clinic.

Dental agenesis is one of the most common developmental anomaly in humans and it is frequently as-sociated with several other oral abnormalities. The present case describes nonfamilial agenesis of per-manent teeth in a twenty-one-year-old boy, with no apparent systemic abnormalities. The treatment in-cluded a personalized and interdisciplinary approach by the means of endodontics, orthodontics, im-plants supported restorations and prosthetic treatments. The treatment plan was thoroughly elaborated using photographic analysis, study models, orthopantomogram, CBCT and cephalograms. Virtual smile design, diagnostic waxing, and mock-up previsualized the treatment objectives. The edentulous spaces were reconstructed by inserting dental implants, and monolithic Zirconia implant supported restorations. The final results showed a highly aesthetic and functional rehabilitation. Periodic checkups have shown that the stability of the result is well maintained and that the implant supported restorations are an op-timal solution for patients with multiple anodontia.

Background: Patients with thromboembolic disease, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Although common professional oral hygiene might not represent a health concern for these patients, anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to investigate the bleeding time of different anticoagulants and antiplatelets during a professional hygiene session adapting the Ivy test to the oral environment; Methods: 93 consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn’s post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; Results: Control patients presented the lowest bleeding time 50 sec, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p=0.004), VKA (p&lt;0.001), DAPT (p&lt;0.001). Conclusions: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT. However, bleeding did not interfere with the oral hygiene ses-sion The optimal period for dental treatment of these patients should be 2-3 hours before the next dose, without the need to temporarily suspend the medication.

Malnutrition is prevalent in patients with chronic kidney disease (CKD), especially those on hemodialysis. Recently, our group described that a new oral nutritional supplement (ONS) for malnourished (or at-risk) hemodialysis patients with a "similar to the Mediterranean diet" model, improved caloric and protein intake, nutritional status and inflammation and oxidation biomarkers. Our aim in this study was to evaluate whether the new ONS, including probiotics, may produce changes in miRNAs expression and its target genes in malnourished hemodialysis patients, compared to individualized diet recommendations. We conducted a randomized, multicenter, parallel-group study in malnourished hemodialysis patients divided in 3 groups (1: Control -C- individualized diet 2: Oral nutritional supplement -ONS- + placebo -ONS-PL- and 3: ONS + probiotics -ONS-PR). Study registration: NCT03924089. The trial was open to the ONS diet or individual dietary advice, but double-blind for the intake of probiotics supplements. MiRNAs and gene expression levels were analyzed by RT-qPCR at baseline and after 3 and 6 months. We observed that the expression of miR-29a and miR-29b increased significantly in patients with ONS-PR at 3 months in comparison with baseline, stabilizing at the sixth month. Moreover, we observed differences between studied groups, where miR-29b expression levels were elevated in patients receiving ONS-PR compared to the control group in the third month. Regarding the gene expression levels, we observed a decrease in the ONS-PR group compared to the control group in the third month for RUNX2 and TNFα. TGFB1 expression was decreased in the ONS-PR group compared to baseline in the third month. PTEN gene expression was significantly elevated in the ONS-PR group at 3-months in comparison with baseline. LEPTIN expression was significantly increased in ONS-PL group at 3-month intervention compared to baseline. The new Oral Nutritional Supplement associated with probiotics; increases the expression levels of miR-29a and miR-29b after 3 months of intervention, modifying the expression of target genes with anti-inflammatory and anti-fibrotic actions. This study highlights the potential benefit of this Oral Nutritional Supplement, especially associated with probiotics, in malnourished patients with chronic renal disease on hemodialysis.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

This case report presents a critical clinical scenario involving a 55-year-old patient who developed severe Plasmodium falciparum malaria with renal complications despite receiving doxycycline prophylaxis while travelling in a malaria-endemic region. The case emphasizes the potential failure of doxycycline prophylaxis and highlights the importance of considering malaria in patients with a history of travel to endemic areas, even if they have adhered to prophylactic treatment. The patient's clinical presentation included fever, extreme fatigue, and loss of consciousness, leading to hospitalization. Laboratory findings revealed severe anaemia, elevated liver enzymes, and impaired renal function, consistent with the criteria for severe malaria. The diagnosis was confirmed by the presence of Plasmodium falciparum parasites on blood smears. Due to limited access to parenteral antimalarial medications, the patient received oral artemether-lumefantrine, resulting in clinical improvement. Supportive care and dialysis played a vital role in the patient's recovery. This case report underscores the need for increased awareness of prophylaxis failure, the challenges of managing severe malaria in non-endemic countries, and the importance of timely and appropriate interventions to improve outcomes in severe malaria cases, particularly those with renal involvement. Further research is warranted to evaluate alternative preventive strategies in regions with drug-resistant malaria strains.

Background: A new access technique was developed to reduce postoperative adverse events after the extraction of impacted maxillary wisdom teeth. Hence, this study aimed to assess the occurrence of adverse events after extraction of maxillary impacted wisdom teeth using traditional or modified access. Methods: Two different surgical incision designs were used for bilateral wisdom tooth extractions in 30 patients. The traditional incision was performed distal to the second molar in the center of the tuberosity, followed by a buccal releasing incision. After tooth extraction the wound was secured by sutures. The new technique consists of an oblique incision from the distal palatal aspect of the tuberosity towards the buccal aspect of the second molar. After tooth extraction, cyanoacrylate glue was used on the wound. Results: Lower pain was reported by patients at the site treated with the new technique (p&lt;0.01). Edema, postsurgical bleeding, and hematoma were similar in both groups. The surgical time was shorter for the new technique (p&lt;0.01). Conclusions: The new technique applied for the extraction of impacted maxillary wisdom teeth reduced postsurgical pain and the duration of surgery.

Hu7691 represents a novel Pan-Akt kinase inhibitor, demonstrating excellent selectivity towards non-AGC kinase families and pronounced inhibitory effects on the proliferation of multiple tumor cell lines. However, there is currently a notable absence of in vivo toxicological research evidence concerning Hu7691. This study represents the first investigation into the 14-day repeated dose toxicity of Hu7691 in male and female Sprague-Dawley (SD) rats. Male rats were administered daily doses of 12.5, 50, 100, and 150 mg/kg, while female rats received doses of 12.5, 25, 50, and 75 mg/kg for 14 consecutive days. Hematological assessments, organ weights, and histopathological examinations revealed corresponding alterations, suggesting potential target organs for toxicity including the spleen, thymus, and gastrointestinal tract. It is worth noting that the test substance may also impact the liver, kidneys, heart, and ovaries. The No Observed Effect Level (NOAEL) was determined to be no greater than 12.5 mg/kg. Based on the observed gender-related toxicity differences in preliminary trials, it is recommended that the high dose reference dose for male animals in formal experiments should not be less than 100 mg/kg, while for female animals, it should be less than 50 mg/kg.

The oral mucosa represents a defense between the external environment and the rest of the body and encompasses several antimicrobial and antiviral mechanisms. Oral mucosal cells are constantly bathed in hypotonic saliva (normally one-third tonicity compared to plasma) and are repeatedly exposed to environmental stresses of tonicity, temperature and pH by the drinks we imbibe (e.g. hypotonic: water, tea, coffee; hypertonic: assorted fruit juices, red wines), as well as of diverse microbial and viral flora. In the mouth, the broad-spectrum antiviral mediator MxA (a dynamin-family large GTPase) is constitutively expressed in healthy periodontal tissues, and also induced by Type III interferons (e.g. IFN-λ1). Endogenously induced human MxA and exogenously expressed human GFP-MxA formed membraneless biomolecular condensates in the cytoplasm of oral carcinoma cells (OECM1 cell line). These condensates likely represent storage granules in equilibrium with antivirally active dispersed MxA. Remarkably, cytoplasmic MxA condensates were exquisitely sensitive sensors of hypotonicity – the condensates in oral epithelium disassembled within 1-2 min of exposure of cells to saliva-like one-third hypotonicity, and spontaneously reassembled in the next 4-7 min. OECM1 cells preloaded with calcein-AM (a reporter of cytosolic “macromolecular crowding”) confirmed unquenching and then requenching of calcein fluorescence during this process. Hypertonicity had little effect on MxA condensates. The spontaneous reassembly of GFP-MxA condensates in oral epithelial cells even under continuous saliva-like hypotonicity was slowed by the protein phosphatase inhibitor cyclosporin A (CsA) and by the K-channel blocker tetraethylammonium chloride (TEA) suggestive of the involvement of the volume-sensitive WNK kinase-protein phosphatase (PTP)-K-Cl cotransporter (KCC) pathway in the regulated volume decrease (RVD) during condensate reassembly in oral cells. Thus, physiologically, hypotonic drinks (water, tea, coffee) trigger a rapid deployment of antiviral MxA throughout the cytoplasm of oral epithelial cells, with subsequent salvage of MxA back into storage granules/condensates.

The health of inmates living in a restricted environment are affected by oral health behaviours and is related to their oral health-related quality of life (OHRQoL). We investigated oral health behaviours and oral symptoms among male inmates and analysed factors related to OHRQoL. Three hundred and seventy-six male inmates in two prisons were investigated using a self-reported questionnaire. The survey items included oral health behaviours, oral symptoms, self-esteem, and OHRQoL level. We analysed cross-correlations and factors related to OHRQoL. Toothbrushing after lunch and dinner was practiced by 83.5% of male inmates. ‘Food impaction’ was experienced by 45.4%. The OHRQoL level among male inmates was low, at 39.90 points. A hierarchical multiple regression model that controlled for general characteristics identified the following OHRQoL factors, in order of significance: trouble biting/chewing (β = -0.307), toothache (β = -0.154), temporomandibular joint disorder (β = -0.099), and periodontal health (β = 0.089). Self-esteem and OHRQoL were not significantly correlated. To ensure oral health in male inmates, the results of this study suggests that an oral health education programme, as well as provision of adequate dental care services, is required to increase appropriate oral health practice rates.