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<0.001), DAPT (p<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.

Non-Vitamin K Oral Anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs—Apixaban, Rivaroxaban, Edoxaban, and Dabigatran—not only as anticoagulants but also as modulators of inflammation via Protease-Activated Receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as FXa and Thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles but also paves the way for future research and clinical applications in inflammation and cardiovascular health

Introduction: Data on peri-operative management of direct-acting oral anticoagulants (DOACs) during transcatheter pacing leadless system (TPS) implantation remain limited. This study aimed to evaluate a standardized DOAC management regime consisting in interruption of a single dose prior to implantation and reinitiation within 6-24 hours; also, patient clinical characteristics associated with this approach were identified. Method Consecutive patients undergoing standard TPS implantation procedure from two Swiss tertiary centers were included. DOAC peri-operative management included the standardized approach (Group 1A) or other different approaches (Group 1B). Results Three hundred and ninety two pts (mean age 81.4±7.3 years, 66.3% male, left ventricular ejection fraction 55.5±9.6%) underwent TPS implantation. Two hundred and eighty two pts (71.9%) were under anticoagulation therapy: 192 pts were treated with DOAC; 90 pts were under vitamin-K antagonist. Patients treated with DOAC less often had structural heart disease, diabetes mellitus, and advanced renal failure. The rate of major peri-procedural complications did not differ between Groups 1A (n=115) and 1B (n=77) (2.6% and 3.8%, p=0.685). Compared to 1B, 1A patients were implanted with TPS for slow ventricular rate atrial fibrillation (AF)(p=0.002), were in better overall clinical status, and were implanted electively (<0.001). Conclusions Standardized peri-procedural DOAC management was more often implemented for elective TPS procedure and did not seem to increase bleeding or thromboembolic adverse events.

We report the case of a 61-year-old woman who was referred to the Oral Surgery and Implantology Unit of the University Hospitals of Geneva to take care edentulous sites after dental avulsions of teeth 11 and 21 following traumatic shock due to endotracheal intubation under general anaesthesia. The dental history revealed that the patient had a history of generalized chronic periodontitis that had been treated several years earlier. Treatment consisted, for the first time to our knowledge, of immediate insertion of implants at sites 11 and 21 with simultaneous bone augmentation in a single surgical procedure and immediate restorations.

Background The coronavirus pandemic has led to the creation of clinical guidelines by a large number of professional medical communities. However, the quality and methodology of development of Russian clinical guidelines has been little studied. The continued relevance of studying the use of DOACs in patients with COVID-19 was the basis for conducting this study. Aim The objective of this study was to assess DOACs consumption and expenditures in Russian Federation during COVID-19 pandemic and to analyse domestic evidence base for the use of DOACs in COVID-19 patients through identifying all publicly available Russian-produced CPGs for the treatment of COVID-19 and assessing their quality as the source of recommendations for the use of oral anticoagulants for the prevention of thrombotic complications in COVID-19 patients. Methods We searched Russian databases for CPGs, published between 2020 and 2023. We identified 7 relevant documents that met our inclusion criteria. Three authors analyzed Russian clinical guidelines using a AGREE II questionnaire. We calculated DOACs DDD consumption according to Russian clinical guidelines and DDD consumption in patients with COVID-19 for the period 2020-2022. Results 7 clinical CPGs were analyzed with the AGREE II tool, it was revealed that experts gave the highest scores for the sections scope and purpose (from 62.98% to 100%), clarity of presentation (from 96.30% to 100%). The lowest scores were given for the sections stakenholder involment (33.33% to 64.81%), rigour of development (from 0% to 49.31%), applicability (from 23.61% to 50%), editory independence ( from 0% to 50%). When comparing the total score, it was found that two clinical guidelines received the highest scores - ROPNIZ (Livzan), ROPNIZ (Drapkina). The minimum score is registered with the NIIOZMM (Khripun) clinical guideline. No guideline received a total score of more than 70%. According to clinical recommendations, the consumption of apixaban and rivaroxaban is 15 DDD (30-day course of therapy), 22.5 DDD (45-day course of therapy). Consumption of apixaban in the Russian Federation in 2020 and 2021 corresponds to the indicators presented in clinical recommendations (in 2020 – 26.59 DDD per patient with COVID-19; in 2021 – 15.75 DDD per patient with COVID-19), and in 2022 – 10.67 DDD, which is below the recommended values. In 2020, consumption of rivaroxaban in the Russian Federation was 26.59 which corresponds to data from clinical recommendations; in 2021, consumption decreased to 7.87 DDD; in 2022 – 5.48 DDD, which is 2.74 times less than recommended.

Several types of guided bone regeneration materials are available with various properties and clinical indications. Among them, dentin-derived matrix from extracted teeth is an excellent alternative to traditional graft materials, such as allografts and xenografts. Different clinical preparation protocols exist: block form versus powder form, demineralized versus non-demineralized form. Out of these methods, demineralization protocols for dentin-derived matrix from extracted teeth have been noted for a wide range of successful clinical outcomes. The purpose of this animal study was to find out the most effective method of demineralizing dentin-derived matrix to result in the highest regenerative ability in the bone graft material in rabbit calvaria. The study conducted a comparative histomorphometric analysis of four groups in distinguished matrix conditions: a control group without graft placement, a non-demineralized dentin-derived matrix graft placement group, a 15-minute demineralized dentin-derived matrix graft placement group, and a 30-minute demineralized dentin-derived matrix graft placement group. Regenerative processes were evaluated three times at 2, 4, and 8 weeks post-graft placement. These groups of rabbits were evaluated randomly in a blinded setting to prevent bias. Among the four groups compared, the group with a 15-minute demineralized dentin-derived matrix graft showed the most efficient bone regeneration in the histomorphometric analysis. Based on this animal study, it was apparent that a 15-minute demineralization of dentin-derived matrix is the preferred preparation protocol to maximize the regenerative potential in the matrix.

This review examines the effects of lingonberry (Vaccinium vitis-idaea L.) on general and oral health. The effects of lingonberry are based on the vitamins, minerals, fibers and polyphenolic compounds it contains. Lingonberry's bioactive substances have a diverse range of antimicrobial, anti-inflammatory, antiproteolytic, anticarcinogenic and antioxidant properties. Research results suggest that lingonberries can have a positive effect on human health. Berries, lingonberry juice/lingonberry nectar/fermented lingonberry juice and polyphenol fractions have been used in clinical studies. Lingonberries balance post-meal blood sugar, free fatty acids and insulin levels. Fermented lingonberry juice reduces Streptococcus mutans, Candida and periodontal pathogen counts, but is probiotic because it favors growth of Lactobacilli. In addition, it increases saliva secretion and thus lowers the risk of oral infections. It lowers the clinical parameters of periodontitis and the active matrix metalloprotease-8, reducing the low-grade inflammation associated with periodontal diseases. More studies on humans are needed.

Ectopic eruption of teeth rarely occurs in the mandibular condyle, orbit, nasal cavity, skin, and maxillary sinus. Ectopic eruption of teeth in the maxillary sinus can be accompanied by chronic and recurrent sinusitis, including headache, facial pain, and numbness. Fibro-osseous lesions in the paranasal sinuses are discovered incidentally on X-ray images and are often asymptomatic. Osteoma is the most common fibro-osseous lesion that develops in the paranasal and nasal sinuses. Herein, we report a rare case of osteoma (exostosis) containing supernumerary teeth within the maxillary sinus. A characteristic pedicled bone lesion with a clear border on computed tomography was the undefined orthopantomogram radiopacity in the left maxillary sinus, and the lesion contained teeth. The tumor was excised using the Caldwell–Luc procedure. Pathologically, the surgical specimen revealed an osteoma. The patient’s symptoms of chronic sinusitis disappeared, and the patient had no symptoms 2 years after the surgery. Because the patient had no history of midface trauma or surgery, the supernumerary teeth were speculated to have migrated during a reactive osteogenic process caused by chronic sinusitis.

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.

The aim is to evaluate a program for direct oral anticoagulants (DOACs) management in nonvalvular atrial fibrillation (NVAF) patients, according to patient profiles, appropriateness of dosing, patterns of crossover, effectiveness and safety. This is an observational and longitudinal retrospective study in a cohort of patients attended in daily clinical practice in a single regional hospital in Spain with a systematic follow-up plan for up to 3 years for patients initiating dabigatran, rivaroxaban or apixaban between JAN/2012-DEC/2016. We analyzed 490 episodes of treatment (apixaban 2.5 mg: 9.4%, apixaban 5 mg: 21.4%, dabigatran 75 mg: 0.6%, dabigatran 110 mg: 12,4%, dabigatran 150 mg: 19.8%, rivaroxaban 15 mg: 17.8% and rivaroxaban 20 mg: 18.6%) in 445 patients. 13.6% of patients on dabigatran, 9.7% on rivaroxaban, and 3.9% on apixaban, switched to other DOACs or changed dosing. Apixaban was the most frequent DOAC switched to. The most frequent reasons for switching were toxicity (23.8%), bleeding (21.4%) and renal deterioration (16.7%). Inappropriateness of dose was found in 23.8% of episodes. Patients taking apixaban 2.5 mg were older, had higher CHA2DS2VASc score and lower creatinine clearance. Patients taking dabigatran 150 mg and rivaroxaban 20 mg were younger, had lower CHA2DS2VASc and higher creatinine clearance. Rates of stroke/transient ischemic attack (TIA) were 1.64/0.54 events/100 patients-years, while rates of major, clinically relevant non-major (CRNM) bleeding and intracranial bleeding where 2.4, 5, and 0.5 events/100 patients-years. Gastrointestinal and genitourinary bleeding were the most common type of bleeding events (BE). On multivariable analysis, prior stroke (RR: 4.2; CI: 1.5-11.8; p=0.006) and age (RR: 1.2; CI: 1.1-1.4; p=0.006) were independent predictors of stroke/TIA. Concurrent platelet inhibitors (RR: 7.1; CI: 2.3-21.8; p=0.001), male gender (RR: 2.1; CI: 1.2-3.7; p=0.0012) and age (RR: 1.1; CI: 1.02-1.13; p=0.005) were independent predictors of BE. This study complements the scant data available on the use of DOACs in NVAF patients in Spain, confirming a good safety and effectiveness profile

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

Purpose: The purpose of this study is to apply the Composite Radiographic Index modified (CRIm) in CBCT scans of patients with Medication related osteonecrosis of the jaws (MRONJ) in order to detect its validity, and corelate the radiologic findings with the clinical staging of the disease. Methods: This study included 43 patients with MRONJ diagnosis and CBCT scans performed in the School of Dentistry and approved by the Research Ethics Committee. Clinical staging for every patient (0-3) was provided according to AAOMS 2022 guidelines. In cases of patients with both jaws affected, each jaw was evaluated independently resulting to 52 CBCT scans. The 52 CBCT scans were assessed under standardized viewing conditions by 2 observers who evaluated independently the following 8 radiologic features: lytic changes, sclerosis, periosteal reaction, sequestration, non-healing extraction sockets and other findings (sinus implication, inferior alveolar canal involvement, jaw fracture). The CRIm index was constructed to assess the extent of osseous changes. The radiologic features were scored as absent (0), localized/single (1), extensive/multiple (2), yielding a theoretical range of 0–12. For statistical analysis Fisher’s exact test and Spearman’s correlation coefficient were performed. Results: A statistically significant association of clinical stage with lytic changes, sequestration and inferior alveolar canal involvement was found. Also, a statistically significant correlation of clinical stage with CRIm index classification was obtained. Conclusions: The CRIm index tends to increase as the clinical stages of MRONJ advance, suggesting a correlation between the clinical stage of MRONJ and the CRIm index.

This study explores the impact on the stability of drying and encapsulation of a camu camu extract (CCX) using the non-thermal, high-throughput electrospraying assisted by pressurized gas (EAPG) technique. The dried and encapsulated products by the EAPG processing techniques were compared in terms of total soluble phenolic compounds, antioxidant activity, and storage stability. Whey protein concentrate (WPC) and zein (ZN) were selected as the protective excipients for encapsulation. Dried and encapsulated products were obtained in the form of microparticles, which were smaller and more spherical in the case of the encapsulates. No significant differences were observed in the total polyphenolic content (TSP), and only relatively small differences in the antioxidant capacity were measured among samples. The generated products were subjected to various storage conditions to assess their stability and the preservation of the TSP and the antioxidant properties, i.e. 0% relative humidity (RH) and 4°C; 0% RH and 21°C; 23% RH and 21°C; 56% RH and 21°C; and UV light exposure. The results indicated that ZN encapsulation notably enhanced the retention of total soluble polyphenols and antioxidant activity compared to WPC and dried CCX, especially in the ratio 2:1 (encapsulating polymer: dried CCX). This study demonstrates the potential of protein-based encapsulation, particularly using ZN, for stabilizing bioactive compounds against degradation mechanisms induced by humidity, temperature, or ultraviolet radiation exposure.

Background and Objectives: The aim of this study was to determine the job-related and individual features that influence BS and depression levels among dentists working in faculties, oral and dental health centres (ODHC) and private clinics. Materials and Methods: This prospective, cross sectional study was carried out on dentists working in different regions of Turkey. Data were collected using an on-line questionnaire created using Google Forms. The questionnaire consisted of demographic data, Maslach BS Inventory (MBI) and Beck Depression Inventory (BDI) sections. Demographics were age, height, weight, marital status, blood type, gender, monthly income, income satisfaction and having enough free time. The dentists were divided into 3 groups as faculty, private clinic and ODHC according to the institutions in which they worked. Results: Of the total 290 dentists enrolled in the study, there were 172 males and 118 females with a mean age of 36.98±5.6 years. 128 of the dentists worked in faculties, 72 in private clinics and 90 in ODHCs. It was observed that women's EE scores were higher than men's (P&lt;0.05). No statistically significant difference was found between the groups when comparing BS and depression scores according to marital status and blood group (P&gt;0.05). There was no significant relationship between emotional exhaustion (EE), depersonalisation (DP), personal accomplishment (PA) and depression scores according to age, BMI and work experience, age, work experience and BMI (P&lt;0.05). It was found that the EE scores of the dentists working in the faculty and private clinic were lower than those of the dentists working in the ODHC (P&lt;0.05). Monthly income was associated with depression (r = -0.35). Conclusions: This study showed that dentists working in ODHCs had more EE. These findings suggest that there is a need for improvement in the working conditions of dentists, particularly in ODHCs.

Vertical and horizontal bone augmentation is one of the most challenging techniques in bone engineering. The use of barrier membranes and scaffolds in guided bone regeneration (GBR) procedures is a common approach for the treatment of lost bone around teeth and dental implants. The aim of this study was to estimate the barrier effects of a synthetic poly (lactic acid/caprolactone) [P(PA/CL)] bilayer membrane for GBR, compared to a porcine collagen bilayer membrane, in the vertical augmentation model on 10–12-months old rat skull without periosteum. The HAp block (diameter: 4 mm, height: 3 mm, porosity:75%, average pore size:150 μm) was placed on the rat skull without a periosteum. The P(LA/CL) membrane (solid layer: 25 μm, porous layer: 175 μm) or the collagen membrane (solid layer, porous layer) was applied onto the HAp block. At 3, 6, and 12 weeks after the surgery, the incised tissues were fixed, decalcified, and stained with hematoxylin and eosin for histological evaluation. The P(LA/CL) membrane remained until 12 weeks and could achieve barrier effects to inhibit cellular invasion from the repositioned soft tissues. Local bone formation occurred in the interconnected pores of HAp at 6 weeks. On the other hand, the collagen membrane did not inhibit cellular invasion for its expansion until 3 weeks, and was absorbed until 6 weeks. The results indicated that the P(LA/CL) membrane might be effective in GBR as occlusive absorbable membrane.

Objectives: Aim to assess the perceptions of virtual learning among dental residents and faculty and employ Regulatory Focus Theory (RFT) to understand the impact of motivational orientations on virtual learning during COVID pandemic. Methods: 46 dental residents and 10 faculty in Upstate New York participated in the study (June -August 2021). Questionnaires were used to collect demographics, perceptions of virtual learning, burnout, and RFT types (promotion and prevention focus). Multiple regression analyses were used to examine factors associated with perceptions of virtual learning and burnout. Results: Overall, 70% of residents and 44% of faculty found virtual learning effective. Younger residents with less experience preferred virtual learning more than their older, experienced peers. Residents trained outside the U.S. and Canada favored in-person learning more than those trained within. Furthermore, residents with a higher promotion focus score found virtual learning more interactive for didactic courses. Additionally, 52% of residents experienced burnout, with a higher incidence among females (p=0.044). Conclusions: Virtual learning is well-received by dental residents and faculty, with potential for continued use post-pandemic. Future efforts should focus on creating an inclusive and supportive educational environment that meets the motivational and well-being needs of dental residents and faculty.

Keywords: Vascular Malformation, Diode Laser, Angioma, Blue light, Conservative

The objective of this study was to compare single-needle arthrocentesis with the conventional two-needle arthrocentesis, as well as, additional intracapsular injection of hyaluronic acid or platelet rich fibrin. 96 patients with established osteoarthritis (OA) (n= 48) or with internal de-arrangement (DD) (n= 48) were assigned for single-needle arthrocentesis with distension of the joint or conventional two-needle arthrocentesis with or without intracapsular injection of the medication (hyaluronic acid- HA or platelet-rich plasma- PRP) performed every month in the period of 6 months. The maximum mouth opening and pain as measured by the visual analog scale (VAS) were compared. Each group exhibited significant improvement: decrease of pain and in-creased mouth opening. Single- puncture technique provided similar pain reduction as two needle approach but provided significantly better results in maximum mouth opening. Reduction of pain was similar when comparing between the OA and DD cohorts, however patients with disc dis-placement reached significantly better mouth opening than OA. Intracapsular application of medication contributed to significant decrease of pain in both HA and PRP groups, with plate-let-rich fibrin being significantly superior in terms of mouth opening increase over HA.

The aim of this study was to evaluate the effect of two different insertion speeds at 8 different insertion torque values ranging from 25-60 during implantation in a dense polyurethane D1 bone model on the placement status and removal torque of dental implants. In this study, 50 pcf single layer polyurethane plates were used. In the study, a total of 320 implant sockets were divided into 2 groups as Group 1 (30 rpm) and Group 2 (50 rpm) in terms of insertion speed. Group 1 and Group 2 were divided into 8 subgroups as 25, 30, 35, 40, 45, 50, 55 and 60 torques. There were 20 implant sockets in each subgroup. During the implantations, implant placement status and removal torque values were assessed. There was a statistically significant difference between the 30 and 50 RPM groups in terms of overall implant placement status (p&lt;0.01). It was found that the removal torque values at 50 RPM were statistically significantly higher than those at 30 RPM (p&lt;0.01). This study showed that in dense D1 bone, the minimum parameters at which all implants could be placed at bone level were 50 torque at 30 rpm and 40 torque at 50 rpm.

A hemostatic sponge prototype was successfully synthesized from fish gelatin as an alternative to mammalian gelatin, which was mixed with alginate in certain combinations and double cross-linking of calcium ions and gamma irradiation at a dose of 20 kGy to improve the characteristics and effectiveness of its function as a local hemostatic agent. There was an improvement in the physicochemical and mechanical properties, porosity index, absorption capacity, biodegradation properties, biocompatibility, and hemocompatibility of the FGAS prototypes compared with the pure fish gelatin sponge. Hemostatic activity tests showed that the means of clotting time, prothrombin time, and activated partial thromboplastin time were shorter in the FGAS prototype than in the negative control, and there was no significant difference compared with the commercial gelatin sponge. The hemostatic mechanism of the FGAS prototype combined a passive mechanism as a concentrator factor and an active mechanism through the release of calcium ions as a coagulation factor in the coagulation cascade process.

Dirofilariosis is an infectious disease caused by species of the Dirofilaria genus. It is manifested by the appearance of a subcutaneous swelling, especially in the eye region. We present the case of a 29-year-old patient that accused facial asymmetry in the right genian region. Following clinical and paraclinical evaluations, the diagnosis of parasitic cyst was established in the context of dirofilariosis with Dirofilaria repens (D. repens). Treatment consisted of surgical excision of the formation associated with prophylactic antibiotic medication. Macroscopic analysis of the excision piece revealed a structure that contains a cystic cavity and a filamentous form with a length of approximately 10 mM and a diameter of 1 mM. This is the first case of dirofilariosis located in the genian region reported in Romania. The overview of this pathology is important to raise awareness among physicians about its presence and its clinical variations.

Background and Objectives: The complications seen after lower impacted third molar surgery affect the quality of life of the patients. The aim of the study was to investigate the efficacy of a single preoperative dose of deflazacort on pain, swelling and trismus following impacted lower third molar surgery. Materials and Methods: This randomised, prospective, double-blind, split-mouth clinical study included 30 healthy individuals with bilaterally impacted lower third molars that was removed for orthodontic purposes between September 2017 and September 2018. Group 1 was given a placebo (single dose vitamin C tablet) and group 2 was given a single 30 mg dose of deflazacort 1 hour prior to the surgery. Pain was evaluated using the visual analog scale for 1 week postoperatively. Edema (in mm) and trismus (in mm) were evaluated preoperatively and on postoperative days 2 and 7. The Mann-Whitney U test was applied for group analysis. p values < 0.05 were considered statistically significant. Results: When postoperative pain scores were evaluated, a significant difference was found between the groups only at the 6th and 12th hours (p0.05). Even high trismus values were recorded on the 2nd day, it was observed that the trismus resolved on the 7th day. There were no significant differences in trismus between the groups at any time point (p>0.05). Evaluation of swelling showed that there was no statistically significant difference between the study and control groups at any time point (p>0.05). No side effect was detected in both the study and the control groups. Conclusions: This was the first split-mouth study evaluating the anti-inflammatory effect of deflazacort after lower impacted third molar surgery. A single dose of 30 mg deflazacort was shown to be effective in reducing pain at 6 and 12 hours postoperatively.

The assortment of low-cost 3D printers for “in-practice” use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: 2 model types (solid or hollow shell) combined with 3 print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100-µm layer thickness using a digital light processing-based 3-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically-acceptability range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). Accuracy of orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.

Little has been written in literature about the clinical comparison of the single use of chlorhexidine (CHX) rather than its combination with cetylpyridinium chloride (CPC). The purpose of this study was to compare the clinical effectiveness of two at-home antiseptic regimens. Healthy subjects scheduled for dental surgery were enrolled. After the surgery, patients were randomly allocated in a first group (Group A) which received a manual ultra soft toothbrush (Mentadent Professional®), an antiseptic toothpaste with 0,12% CHX and Vitamin B3 (Mentadent Professional Azione Intensiva Gengive®) and an antiseptic mouthwash with 0,12% CHX and 0,07% CPC. The second group (Group B) received solely an antiseptic mouthwash with 0,2% in conjunction with Anti Discoloration System (Curasept ADS/DNA®) and were encouraged to use their usual toothbrush and toothpaste. Patients were instructed to use the products twice a day and to rinse for 30 seconds. On day 7, patients were examined for the Early Healing Score, Visual Plaque Index of the sutures, Numerical Rating Scale and mouthwash taste. Group A showed a statistically significant levels of EHS and taste satisfaction. The regimen based on CHX associate with vitamin B3 in the toothpaste and CPC in the mouthwash resulted in superior clinical outcomes and satisfaction compared to solely CHX.

Background: Two explored EDA1 variants regulate the biological behaviors of human dental pulp stem cells (hDPSCs), such as proliferation and migration, as well as their effects on odontogenic differentiation, providing a theoretical basis for further exploration of the mechanisms underlying EDA1-induced tooth development. Methods: The experimental groups included a wild-type EDA1 group (Wt), non-syndromic tooth agenesis variants EDA1 group (NSTA-A259E, NSTA-S374R), syndrome type variant EDA1 group (STA-H252L), and an empty vector control group (PCR3/NC). CCK-8 method was used to investigate the proliferative activity of hDPSCs. The cell cycle distribution of hDPSCs was detected by flow cytometry; The cell migration ability was assessed using the cell scratch and Transwell tests; Odontogenic differentiation medium was used to induce mineralization of hDPSCs, followed by statistical analysis. RNA-Seq revealed that FOS, JUN and other genes were found to be enriched in MAPK signaling pathway and osteoclast differentiation pathway. qPCR was used to detect mRNA expression of hub genes (FOS and JUN). Results: Compared with the NSTA-EDA1 and STA-EDA1, Wt-EDA1 promotes the proliferation and transformation of hDPSCs from the G0/G1 phase to S phase (p<0.01), with no significant difference between NSTA-EDA1 and STA-EDA1 (p>0.05). Wt-EDA1 also upregulated hDPSCs cell migration compared to NSTA-EDA1 and STA-EDA variants, as demonstrated by migration assays (p<0.01). NSTA-EDA1 and STA-EDA1 variants inhibited the odontogenic differentiation of hDPSCs compared to the Wt group, as shown by Alizarin red staining and ALP staining (p<0.01). RNA sequencing revealed that the differentially expressed genes FOS and JUN were enriched in the MAPK signaling pathway and osteoclast differentiation. Compared with Wt-EDA1, EDA1 variants lost the ability to promote c-FOS mRNA expression, as confirmed by qPCR. Conclusions: EDA1 variants fail to the promote c-FOS mRNA expression in hDPSCs, thereby inhibiting odontogenic differentiation and losing the ability to enhance the proliferation of hDPSCs.

Background Oral anticoagulation (OAC) for atrial fibrillation (AF) patients is administered frequently. Vitamin K antagonist (VKA) and direct oral anticoagulants (DOACs) prevent thromboembolic events, but information about the quality of life (QoL) and patient satisfaction, related to both anticoagulants, is limited. Methods REGUEIFA is an observational and multicentre study that included patients with AF diagnosis treated by cardiologist. Those on OAC, VKA, and DOACs were selected. The EuroQol-5D (EQ-5D) questionnaire evaluated QoL, and the ACTS (Anti-Clot Treatment Scale) questionnaire investigated patient satisfaction with OAC. Results From a total of 1007 patients, 904 patients were on OAC, 532 on VKA and 372 on DOACs. In total, 846 patients completed the EQ-5D questionnaire, with results significantly worse in patients on VKA than on DOACs: (1) mobility limitations (37.6% vs. 24.2%, p

Worldwide, oral lesions and cancers are still being significant public health conditions. Thus, an introduction of new oral healthcare protocols is becoming essential. Oral diseases are related to many causative factors, manly dental plaque/biofilm due to poor hygiene. New anti-biofilm therapies are needed to develop. The strategies of anti-biofilm therapies should help to control biofilm formation and microbial attachment to dental surfaces. The present review aimed to provide a comprehensive over-view on evidence related to the potential utility of topical oxygen therapy (BlueM formula) as novel oral care therapies in clinical practice.

In the present study, a multilayer high barrier thin blown film based on a polybutylene adipate terephthalate (PBAT) blend with polyhydroxyalkanoate (PHA), and composed of four layers, including a cellulose nanocrystals (CNC) barrier layer and an electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) hot-tack layer, was characterized in terms of surface roughness, surface tension, migration, mechanical and peel performance, barrier properties and disintegration rate. The results showed a material with a smooth surface. The overall migration test showed that the material was suitable for its use as a food contact layer. The addition of the CNC interlayer had a significant effect on the mechanical properties of the system, drastically reducing the elongation at break and, thus, the flexibility of the material. However, the material retained its elastic modulus and tensile strength. The CNC coating had a negative impact on the peeling strength, weakening the inherently strong interlayer adhesivity of the electrospun PHBV fibers. The multilayer had a good barrier to water vapor, and especially to oxygen, with its permeance reduced by up to a 90 % when the CNC layer was present. Finally, the monolayer blend film disintegrated in a period of less than 55 days in a laboratory-scale composting experiment, while the multilayer system disintegrated in 60 days. Overall, the multilayer system formed a fully compostable structure with great potential for use in food packaging applications.

Background: This study stands as a pioneer in the histological evaluation of the biological behavior of a novel implant design featuring decompressive cervical blades. Hence, the aim of the present study was to evaluate the healing outcome in cortical regions at where decompressive protocols were adopted using implants equipped with blades. Materials and methods: Blades with varying diameters were integrated into the coronal portion of the implant to prepare the cortical region of rabbit tibiae. The blade diameters differed from the implant collar by the following amounts: control group (0 µm), +50 µm, and +200 µm. Results: No marginal bone loss was detected. Instead, all implants exhibited new bone formation in the coronal region. Complete closure was observed in the CG-0 group, as well as in the TG-50 and TG-200 groups, despite the presence of marginal gaps without primary bone contact at installation. In the apical region, most implants breached the cortical layer. Nevertheless, new bone formation in this region completely closed the osteotomy, effectively isolating the internal environment of the tibia from the external. Conclusions: The use of a blade attached to the implant body enabled precise preparation of the cortical layer, allowing for controlled decompression in the targeted area. This technique resulted in optimal osseointegration with no loss of marginal bone, and complete restoration of marginal gaps ranging from 0 µm to 200 µm.

This study aims to provide an updated overview of the systematic evaluation and management of Post-Traumatic trigeminal neuropathic pain (PTTN) resulting from dental procedures or trauma. PTTN arises following an injury to the trigeminal nerve, which is responsible for sensory and motor functions in the maxillofacial region. The etiology encompasses various dental procedures and craniofacial trauma, leading to a spectrum of symptoms, from tingling to severe pain. Diagnostic challenges stem from the absence of standardized criteria and the overlap with focal neuralgia, necessitating comprehensive evaluation. Misdiagnosis can result in prolonged suffering and unnecessary procedures. Successful management hinges on prompt diagnosis and interdisciplinary collaboration, with early intervention crucial in mitigating chronicity. While nerve recovery post-trauma is challenging, preventive measures through accurate evaluation and treatment are paramount.  Management for PTTN includes non-invasive and surgical interventions. Non-invasive intervention includes systematic and local pharmacological management. This review enhances uniformity in PTTN evaluation and treatment approaches despite standardized study limitations.

Oral candidiasis is a common problem among immunocompetent patients. The frequent resistance of Candida strains to popular antimycotics makes it necessary to look for alternative methods of treatment. The authors conducted a systematic review following the PRISMA 2020 guidelines. The objective of this review was to determine whether curcumin-mediated aPDT and blue light could be considered as an alternative treatment for oral candidiasis. PubMed, Google Scholar and Cochrane Library databases were searched using a combination of the following keywords: (Candida OR candidiasis oral OR candidosis oral OR denture stomatitis) AND (curcumin OR photodynamic therapy OR aPDT OR photodynamic antimicrobial chemotherapy OR PACT OR photodynamic inactivation OR PDI). The review included in vitro laboratory studies with Candida spp., in vivo animal studies, and randomized control trials (RCTs) involving patients with oral candidiasis or prosthetic stomatitis, published only in English. The method of elimination of Candida species in the studies was curcumin-mediated aPDT. 757 studies were identified. Following the analysis of the titles and abstracts of the studies, only 42 studies were selected for in-depth screening, after which 26 were included in this study. All studies evaluated the antifungal efficacy of curcumin-mediated aPDT against C. albicans and non-albicans Candida. In studies conducted with planktonic cells solutions, seven studies demonstrated complete elimination of Candida spp. cells. The remaining studies demonstrated only partial elimination. In all cases, experiments on single-species yeast biofilms demonstrated partial, statistically significant inhibition of cell growth and reduction of biofilm mass. In vivo, curcumin-mediated aPDT has shown good antifungal activity against oral candidiasis also in an animal model. However, its clinical efficacy as a potent therapeutic strategy for oral candidiasis requires further RCTs.

We present a case report of a 26-years-old female suffering from Coffin Siris Syndrome, who underwent orthodontic treatment and surgery to solve her malocclusion and improve her aes-thetics and functional occlusion. Methods: The presurgical phase involved multibracket self-ligating attachments, Damon prescription. The patient underwent maxillofacial surgery to correct the severe skeletal malocclusion and relocate the bone bases in the right relationship. The post-surgical orthodontic treatment was performed to complete the alignment. Results: The pa-tient improved her aesthetics and functional abilities. Conclusions: Syndromic patients can un-dergo orthodontictreatment if comorbidities and collaboration allow it. Support and collaboration of families and psychotherapists must be considered, but clinical cases of syndromic patients can be faced and solved. Obviously, each syndromic patient is considered unique, and the risk-benefit ratio must be correctly assessed for each one.

Mesenchymal stem cells due to their multipotent ability are considered one of the best candidates to be used in regenerative medicine. The most used source of those stem cells long the last decades was the bone marrow, despite its limited cell resources and the painful and very invasive surgical treatment. Therefore, the scientific community investigated many alternative sources for the harvesting of these stem cell subpopulations. Adipose tissue attracted the biggest interest thanks to special features, such as great tissue abundance, easy availability, and in the end the large amount of positive mesenchymal stem cells. Once it was verified that these stem cell subpopulations possess the same bone marrow differentiation potential, it became evident that they would be the ideal candidate to be used in regenerative and tissue engineering applications. Even the regenerative use of these cells long become a sensitive point because not all the acquired phenotypes resulted in the best source for plastic procedures. As documented in the literature, the ideal fillers for regenerative is represented by stem cell population. Therefore, it became crucial to investigate any kind of biological mechanism on the differentiative ability of those mesenchymal stem cells, especially their regulative factors. One of the most studied and important regulators are the miRNAs. Indeed, miRNA play a crucial role in the differentiation process of adipose stem cell cultures isolated from patients or obtained by commercial cell lines toward osteocytes, chondrocytes, and adipocytes differentiated populations.

(1) Background : When placing implants in the maxillary posterior region with insufficient alveolar bone, a maxillary sinus elevation is necessary. Autogenous bone, though biologically ideal, poses risks and discomfort due to donor site harvesting. Block-type autogenous tooth bone graft material, made from the patient’s own extracted tooth, offers similar biological stability without these drawbacks; (2) Methods : This study observed the progress of 19 implant patients who were treated with maxillary sinus elevation procedures using block-type autogenous tooth bone graft material at the Daegu Catholic University Medical Center. Extracted teeth were processed into demineralized tooth block bone. After elevating the sinus membrane, implants and the tooth bone graft material were placed in the space, and the bony window was repositioned. Postoperative evaluations through clinical observation and radiographic imaging assessed sinus membrane elevation, alveolar bone height increase, and implant osseointegration; (3) Results : Results showed proportional increases in alveolar bone height to the graft material size, with long-term stability. No postoperative complications occurred, even with sinus membrane perforation, and implants remained stable; (4) Conclusions : The study concludes that maxillary sinus lifts using block-type autogenous tooth bone graft material provide excellent bone induction and biocompatibility, making it a highly beneficial method for both dentists and patients.

Although researchers have proposed various indentation size effect (ISE) models, these models often involve different form and number of parameters that can make our wonder which is the best in existed ISE models. Three types of ISE test data, namely, normal ISE, reverse ISE and transition of normal to reverse ISE, are used to evaluate the sixteen ISE models. The comparatively study indicates that H-J, N-G-Fs, N-G-H, N-G-A and N-G-Qs models can accurately predict the normal ISE. The reason for this is that the friction stress that is not related to dislocation activities or the indentation size effect of plastic zone has been introduced into these models. Therefore, these two factors should be considered in future ISE models. The sixteen ISE models are originally proposed to describe the normal ISE of different materials. However, to our surprise, some of these models are able to capture the reverse ISE and the transition of normal to reverse ISE of different materials. The determination coefficients (DC) of the sixteen ISE models are also determined for different materials. For reverse ISE, the highest DC value for NiCSi, TC4 and PED Ni are given by the EXP, N-G-Fs and N-G-A models, respectively. For the transition of normal to reverse ISE, the N-G-YC, N-G-Fs, and N-G-H models produce the maximum DC for ZrO2, Cu and Y2O3-ZrO2, respectively. Moreover, the mean DC of the N-G-Fs model is the maximum among the sixteen ISE models, followed by the N-G-H model, but they cannot accurately predict the reverse ISE. Therefore, the N-G-Fs and N-G-H models should be further modified to accurately predict the reverse ISE.

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

The aim of this study was to evaluate the use of a flexible synthetic polymer bone graft to provide implant stability in the absence of implant stability during implant placement in a dense cortical bone model. Sockets were prepared on polyurethane blocks according to the standard implant socket drilling protocol in the control group, both oversizing and deepening in group 2, and oversizing only in group 3. In groups 2 and 3, flexible synthetic polymer bone grafts were placed in the sockets prior to implant placement. The implants were placed at bone level in all groups. The highest torque value obtained was recorded as the insertion torque. 75 implant sites in 3 groups were included in the study. The torque values of the implants in the control group were significantly higher than those of the implants with the oversized and deepened sockets and the oversized-only sockets (p&lt;0.05; p&lt;0.01).The torque values of the implants with the oversized and deepened sockets were significantly higher than those of the implants with the oversized-only sockets (p&lt;0.01). In this study, flexible synthetic polymer bone graft was shown to be effective in achieving implant stability in the management of implants with loss of primary stability.

Systematic reviews represent a powerful instrument to summarize the existing evidence in medical literature. However, articles for a systematic review are hard to identify, and mostly require a structured search of the literature through a number of databases, using keyword-based search strategies, followed by the painstaking manual selection of pieces of evidence that are pertinent to the query. A.I. algorithms may offer solutions to reduce the workload on investigators. We applied BERTopic, a newer and much-recognized transformer-based topic-modeling algorithm, to two datasets of 6137 and 5309 articles of newly published systematic reviews in the area of peri-implantitis and bone regeneration in implant dentistry. In the two datasets, BERTopic identified 14 and 22 clusters, respectively, and it automatically created labels describing the nature of the topics for each individual cluster based on semantic interpretation of their titles. Most themes regarded the query theme, but in both conditions, BERTopic also uncovered articles related to off-themes, which composed around 30% of the dataset—with sensitivity up to 0.79 and specificities of at least 0.99. Our results suggest that adding a topic-modeling step to the screening process could potentially save working hours for researchers involved in systematic reviews of the literature.

Intermittent religious fasting increases a risk of hypo- and hyperglycemia in individuals with diabetes, but its impact in those without diabetes is poorly investigated. The study aim was to examine the effects of religious Bahá'í fasting (BF) on glycemic control and variability and compare these effects with time-restricted eating (TRE). In a three-arm randomized controlled trial, 16 subjects without diabetes were assigned to a BF, 16:8 TRE or control group. Continuous glucose monitoring and food intake documentation was conducted before and during the 19 days of intervention, and 24-hour mean glucose, glycemic variability indices, and glucotypes were assessed. BF and TRE groups, but not the control group, markedly reduced the daily eating window while maintaining macronutrient composition. Only the BF group decreased caloric intake (-677.8 ± 357.6 kcal, p=0.013), body weight (-1.92 ± 0.95 kg, p=0.011) and BMI (-0.65 ± 0.28 kg, p=0.006). Higher maximum glucose values were observed during BF in the within-group (+1.41 ± 1.04, p=0.039) and between-group comparison (BF vs. Control: p= 0.010 and TRE vs. BF: p= 0.022). However, there were no alterations of 24-hour mean glucose, intra- and inter-day glycemic variability indices, or glucotypes in any group. Proportions of time above and below range (70-180mg/dl) and HbA1c values remained unchanged. BF and TRE do not exhibit negative effects on glycemic control and variability in subjects without diabetes.

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.

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

Imbalance of homeostasis between the microbial communities and the host system leads to dysbiosis in oral micro flora. DMTU (1,3-di-m-tolyl-urea), is a biocompatible compound that was shown to inhibit Streptococcus mutansbiofilms by inhibiting its communication system (quorum sensing). Here, we hypothesized that DMTU is able to inhibit multispecies biofilms. We developed a multispecies oral biofilm model comprising an early colonizer Streptococcus gordonii, a bridge colonizer Fusobacterium nucleatum, and late colonizers Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans. We performed comprehensive investigations to demonstrate the effect of DMTU on planktonic cells and biofilms. Our findings showed that DMTU inhibits and disrupts multispecies biofilms without bactericidal effects. Mechanistic studies revealed significant down regulation of biofilm and virulence related genes in P. gingivalis. Taken together, our study highlights the potential of DMTU to inhibit polymicrobial biofilm communities and their virulence.

The aim of this research is to investigate the influence of model height employed in the deep drawing of orthodontic aligner sheets on force transmission and aligner thickness. Forty sheets (Zendura FLX) were thermoformed over four models of varying heights (15, 20, 25, and 30 mm). Normal contact force generated on the facial surface of the upper right central incisor (Tooth 11) was measured using pressure-sensitive films. Aligner thickness around Tooth 11 was measured at five points. A digital caliper and a micro-computed tomography (µ-CT) were employed for thickness measurements. The normal contact force exhibited an uneven distribution across the facial surface of Tooth 11. Model 15 displayed the highest force (88.9±23.2 N), while Model 30 exhibited the lowest (45.7±15.8 N). The force distribution was more favorable for bodily movement with Model 15. Thickness measurements, conducted using a digital caliper and µ-CT, revealed substantial thinning of the aligner after thermoforming. This thinning was most pronounced at the incisal edge (50% of the original thickness) and least at the gingivo-facial part (85%). Additionally, there was a progressive reduction in aligner thickness with increasing model height, which was most significant on the facial tooth surfaces. We conclude that the thermoplastic aligner sheets undergo substantial thinning during the thermoforming process, which becomes more pronounced as the height of the model increases. As a result, there is a decrease in both overall and localized force transmission, which could lead to increased tipping by the aligner and a diminished ability to achieve bodily movement.

Background: Smad4, a critical tumor suppressor gene, plays a significant role in pancreatic biology and tumorigenesis. Genetic background and sex are known to influence phenotypic outcomes, but their impact on pancreatic weight in Smad4-deficient mice remains unclear. This study investigates the impact of Smad4 deficiency on pancreatic weight in F1 mice from diverse Collaborative Cross (CC) lines, focusing on the influence of genetic background and sex. Methods: F1 mice were generated by crossbreeding female CC mice with C57BL/6J-Smad4tm1Mak males. Genotyping confirmed the presence of Smad4 knockout alleles. Mice were housed under standard conditions, euthanized at 80 weeks, and their pancreatic weights were measured, adjusted for body weight, and analyzed for effects of Smad4 deficiency, sex, and genetic background. Results: The overall population of F1 mice showed a slight but non-significant increase in adjusted pancreatic weights in heterozygous knockout mice compared to wild-type mice. Sex-specific analysis revealed no significant difference in males but a significant increase in adjusted pancreatic weights in heterozygous knockout females. Genetic background analysis showed that lines CC018 and CC025 substantially increased adjusted pancreatic weights in heterozygous knockout mice. In contrast, other lines showed no significant difference or varied non-significant changes. The interplay between genetic background and sex further influenced these outcomes. Conclusion: Smad4 deficiency affects pancreatic weight in a manner significantly modulated by genetic background and sex. This study highlights the necessity of considering these factors in genetic research and therapeutic development, demonstrating the value of the Collaborative cross-mouse population in dissecting complex genetic interactions.

Enhancement of orthodontic tooth movement (OTM) through local administration of biofunctional molecules has become increasingly significant, particularly for adult patients seeking aesthetic and functional improvements. This comprehensive systematic review analyzes the efficacy of various biofunctional molecules in modulating OTM, focusing on the method of administration and its feasibility, especially considering the potential for topical application. A search across multiple databases yielded 36 original articles of experimental human and animal OTM models, which examined biofunctional molecules capable of interfering with the biochemical reactions that cause tooth movement during orthodontic therapy, accelerating the OTM rate through their influence on the bone metabolism (Calcitriol, Prostaglandins, Recombinant human Relaxin, RANKL and RANKL expression plasmid, growth factors, PTH, osteocalcin, vitamin C and E, biocompatible reduced graphene oxide, exogenous thyroxine, sclerostin protein, a specific EP4 agonist (ONO-AE1-329), carrageenan and herbal extracts). The results indicated a variable efficacy in accelerating OTM, with Calcitriol, Prostaglandins (PGE1 and PGE2), RANKL, growth factors and PTH, among others, showing promising outcomes. PGE1, PGE2 and Calcitriol experiments had statistically significant outcomes in both human and animal studies, and, while other molecules underwent only animal testing, they could be validated in the future for human use. Notably, only one of the animal studies explored topical administration, which also suggests a future research direction. This review concluded that while certain biofunctional molecules demonstrated potential for OTM enhancement, the evidence is not definitive. The development of suitable topical formulations for human use could offer a patient-friendly alternative to injections, emphasizing comfort and cost-effectiveness. Future research should focus on overcoming current methodological limitations and advancing translational research to confirm these biomolecules' efficacy and safety in clinical orthodontic practice.

Sinonasal carcinomas are aggressive neoplasms that present a high morbidity and mortality rate with unfavorable prognosis. This group of tumors exhibits morphological and genetic diversity. Genetic and epigenetic alterations in these neoplasms are currently targets for diagnosis and treatment. The most common type of cancer originated in the sinonasal tract are sinonasal squa-mous cell carcinomas (SNSCC), which presents different histological patterns and variable his-tological aggressiveness. A significant number of alterations have been reported in sinonasal tu-mors, including deficiencies in the SwItch/Sucrose non-fermentable (SWI/SNF) chromatin remod-eling complex. In the sinonasal tract, deficiencies of the subunits SMARCB1/INI1, SMAR-CA4/BRG1 and SMARCA2 have been noted in carcinomas, adenocarcinomas, and soft tissue tu-mors with distinctive high-grade morphology and fatal prognosis. Objective: To identify the status of the SWI/SNF complex using immunohistochemistry in sinonasal squamous cell carci-nomas and its association with morphology and survival. Methods: A total of 1582 SNSCC cases were analyzed, selecting those with high-grade malignancy morphology, which were then evalu-ated immunohistochemically for SMARCB1 and SMARCA4 proteins. Their expression was compared with the biological behavior and survival of the patients. Results: Among the SNSCC, 47% corresponded to the non-keratinizing squamous cell carcinoma (NKSCC) type with high-grade characteristics, 40% were keratinizing squamous cell carcinomas (KSCC), 9% were SMARCB1-deficient carcinomas, and 4% were SMARCA4-deficient carcinomas. Mosaic expres-sion for SMARCB1 (NKSCC 33%, KSCC 21.9%) and SMARCA4 (NKSCC 14.6%, KSCC 12.2%) was identified, showing an impact on tumor size and progression. Conclusions: We identified that the mosaic expression of INI1 in NKSCC exhibited a worse prognosis compared to intact carcinomas and was similar to SMARCB1-deficent carcinoma.

The popularity of multiparticulate formulations (MPs) as a paediatric dosage form continues to increase. MPs comprise of multiple small units that are easy-to-swallow. Currently, MPs are commonly manufactured into unit doses that are either swallowed whole or opened prior to administration. While this is an acceptable approach, dosing is envisioned to be optimized with a ‘standard’ paediatric device which can better harness the flexible dosing potential of MPs. We evaluated a novel oral syringe (SympfinyTM) that is being developed as a tool to dispense and administer MPs to children. Forty children, 4-12 years old, received 0.5, 1.2, and 2.0 mL doses of placebo MPs using the oral syringe with spring water or a drink of choice to complete sample intake. Acceptability was recorded as those able to completely swallow the dose and participants also rated dose acceptability on a 5-point scale. The ability to completely swallow the dose decreased as dose volume increased; the smallest dose was completely swallowed by 87.5% (35/40) children, and 69.4% (27/39) of children confirmed their willingness to take the sample as a daily medicine. Larger doses, 1.2 and 2.0 mL, gave values of 55% and 57.5% for the doses completely swallowed and 58.8% and 51.72% for willingness to take the sample as a daily medicine, respectively. Use of a drink of choice showed no increase in swallowability as compared with water. The novel oral syringe being developed is an appropriate device for dispensing doses flexibly and administering neutral tasting MPs directly to the mouth in the lower dose range without the need for a co-administration vehicle in children aged 4-12 years.

(1) Background: Tooth extraction is one of the oldest and most well-known surgical procedures in dental medicine. It is still routinely performed to date by both general practitioners, oral surgeons, and dental undergraduates. The Benex extraction system allows for the extraction of teeth in vertical direction, which avoids most trauma against the surrounding alveolar bone and soft tissues; (2) Methods: The study included 56 patients who were recruited from the department of Oral Surgery at the Faculty of Dental Medicine, Medical University – Plovdiv. Patients were divided into two groups of 28 patients – Group I (control group) and Group II (study group). For each group the success of the extraction, buccal cortical plate preservation, pain experience and early wound healing were assessed; (3) Results: There was no statistical significance between the success of the extractions in both groups. The Benex extractions preserved the buccal cortical plate in 95% of the cases, whereas the forceps extractions only in 71.8%, which shows a statistical significance. On the seventh day patients in group II reported less pain, without a significant difference. There was a significantly bigger number of completely healed extraction wounds on the 10th day; (4) Conclusions: Atraumatic extractions allow for more hard and soft tissues to be preserved in the extraction site. This is all crucial for the successful outcome and aesthetically pleasing results of a following prosthetic or implant restoration.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

Severe early childhood caries remains the most common chronic disease affecting children. Its multifactorial etiology has established a controversy about which risk factors were more significant to its development. Therefore our study aimed through meticulous statistical analysis to arrange the “well agreed upon” common risk factors in order of significance, to aid the clinician in tailoring an adequate preventive program for this affected age group. The study reshuffled the risk factors contributing to severe early childhood caries and placed them in the order of their significance as follows: snacking of sugary food several times a day, increased number of siblings to 3 or more, night feeding, child self-employed brushing, mother caries experience, 2 siblings, on demand feeding, once/day sugary food, sharing utensils, 1 Sibling, male gender, father’s education, late first child dental visit, brushing time, mother’s education, no dental visit, decreased brushing frequency & no night brushing.

In this study, a novel oral formulation of berberine hydrochloride (BBH) hydrogel was successfully synthesized through physical cross-linking using chitosan (CS) and carboxymethyl-β-cyclodextrin (CMCD). The characterization results confirmed the successful synthesis of CS/CMCD hydrogel and the subsequent loading of BBH into this composite (CS/CMCD/BBH) was effectively accomplished. BBH was used as a model drug and the resulting hydrogel demonstrated a sustained drug release profile. In addition to its improved solubility and sustained release characteristics, the hydrogel exhibited excellent antibacterial activity against common pathogens such as Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Candida albicans (C. albicans). Additionally, in vitro studies indicated that the hydrogel was not cytotoxic to NIH3T3 and HaCaT cells, suggesting its safety for biomedical applications. This lack of cytotoxic effects, combined with the mechanical strength, solubility improvements, and antibacterial properties of the hydrogel, positions the CS/CMCD/BBH hydrogel as a promising candidate for effective oral delivery of BBH. By addressing the solubility and delivery challenges of BBH, this hydrogel offers a viable solution for the oral administration of berberine hydrochloride, with potential applications in various biomedical fields.

Background:The association between ABO and Rh blood groups and diseases is an intriguing topic that continues to be studied. However, how mandibular symmetry may vary by blood group has not been investigated. This study explored the relationship between these blood groups and mandibular condyle and ramal asymmetries in the Turkish adult population. Methods:The study included 149 adult patients (67 males and 82 females) without systemic diseases or temporomandibular disorder complaints. Asymmetry was assessed in panoramic radiographic images using a formula developed in a previous study. The chi-square and Kruskal-Wallis tests were used to analyze differences among ABO groups while the Mann-Whitney U test was used for Rh groups. Results:There were no statistically significant differences among the ABO blood groups, nor the Rh groups, in terms of sex, Rh factor, and age distribution. However, a comparison of the ABO and Rh blood groups revealed that condylar asymmetries were significantly more common in the AB group. Conclusions:These results suggest that mandibular asymmetry may be associated with the ABO blood group. These findings may guide future research to gain a deeper understanding of the relationship between mandibular asymmetry and blood groups.

Background: Oral cancer (OC) is serious health concerning issue that has a high fatality rate. The oral cavity has seven kinds of OC, including the lip, tongue, and floor of the mouth, as well as the buccal, hard palate, alveolar, retromolar trigone, and soft palate. The goal of this study is to look into new biomarkers and important pathways that might be used as diagnostic biomarkers and therapeutic candidates in OC. Methods: Publicly available repository the Gene Expression Omnibus (GEO) was responsible to collect OC-related datasets. GSE74530, GSE23558, and GSE3524 microarray datasets were collected to apply analysis. Minimum cut-off criteria of |log fold-change (FC)| > 1 and adjusted p < 0.05 were applied to figure out the up-regulated and down-regulated differential expression genes (DEGs) from the three datasets. After that only common DEGs in all three datasets were collected to apply further analysis. Gene ontology (GO) and Pathway analysis were implemented to explore the functional behaviors of DEGs. Then protein-protein interaction (PPI) networks were built to identify the most performed genes, clustering algorithm was also implemented to identify complex parts of PPI. TF-miRNA networks were also constructed to study deeply about OC-associated DEGs. Finally, top gene performers from PPI networks were used to apply drug signature analysis. Results: After applying filtration and cut-off criteria 2508, 3377, and 670 DEGs were found for GSE74530, GSE23558, and GSE3524 respectively, and 166 common DEGs were found in every dataset. The GO annotation remarks that most of the DEGs were associated with the terms of type I interferon signaling pathway. The pathways of KEGG reported that the common DEGs are related to the Cell cycle and Influenza A. The PPI network holds 88 nodes and 492 edges and CDC6 had the highest number of connections. 4 clusters were identified from the PPI. Drug signatures doxorubicin and resveratrol showed high significance according to the hub genes. We anticipate that our bioinformatics research will aid in the definition of the pathophysiology and the development of new therapies for OC.

Objective: To determine the effect of sandblasting before and after sintering on the surface roughness of zirconia and the micro-tensile bond strength of a pressable veneering ceramic to zirconia. Methods: Pre-sintered zirconia blocks (IPS e.max ZirCAD, Ivoclar Vivadent) were divided into a control group (CTR, no surface treatment) and four test groups of three specimens each: Pre-S-30, Pre-S-50, Pre-S-110 were sandblasted with 30µm SiO2, 50µm Al2O3 and 110µm Al2O3 particles respectively, before sintering, Post-S-30 was sandblasted with 30µm SiO2 after sintering. For each treatment, the surface roughness was measured (Ra, Perthometer M4P, Mahr Perthen). After sintering the zirconia blocks, a liner and a pressable ceramic (IPS e.max ZirPress, Ivoclar Vivadent) were fired. Sixteen micro-bars were obtained from each block and submitted to the micro-tensile bond strength (µTBS) test. Data were analyzed with one-way ANOVA. Any correlation between Ra and µTBS was evaluated (Sperman test). Results: Sandblasting before sintering with 110µm Al2O3 (Ra=3.44±0.44µm), 50µm Al2O3 (Ra=2.32±0.46µm), and 30µm SiO2 (Ra=1.22±0.22µm) resulted in significantly higher roughness than sandblasting after sintering with 30µm SiO2 (Ra=0.46±0.11µm). The highest µTBS was measured when the sintered zirconia was sandblasted with 30μm SiO2 (26.79±14.80 MPa), which was significantly different from that of specimens that were sandblasted before sintering (Pre-S-30=20.90±11.70; Pre-S-50=21.27±15.19; Pre-S-110=23.99±16.83) or were not treated (CTR=17.44±14.03). Conclusions: Sandblasting zirconia before sintering enhances the surface roughness proportionally to the particle size of the sand used. Sandblasting with 30µm SiO2 after sintering appeared to improve bonding between the veneering ceramic and zirconia. Clinical Significance: Sandblasting with 30µm SiO2 after sintering may improve bonding between veneering ceramics and zirconia, thus reducing ceramic fractures/chippings.

Cartilage degeneration is a characteristic of osteoarthritis (OA) which is often observed in aging populations. This degeneration is due to the breakdown of articular cartilage (AC) mechanical and tribological properties, primarily attributed to lubrication failure. Understanding the reasons behind these failures and identifying potential solutions could have significant economic and societal implications, ultimately enhancing the quality of life. This review provides an overview of developments in the field of AC, focusing on its mechanical and tribological properties. The emphasis is on the role of lubrication in degraded AC, offering insights into its structure and function relationship. Further it explores the fundamental connection between AC mechano-tribological properties and the advancement of its degradation and puts forth recommendations for strategies to boost its lubrication efficiency.

This study investigated the efficacy and safety of a propolis mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multi-centered randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. Results revealed that the PMEC group showed significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p&lt;0.0001) at 8 weeks, including substantial reductions in IL-1β, PGE2, MMP-8, and MMP-9 levels compared to baseline. While clinical parameters trended towards improvement in both groups, inter-group differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.

The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, melatonin, whose role in the treatment of mucositis has recently been investigated, offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives.

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.

Obstructive sleep apnea (OSA) is a prevalent source of sleep-disordered breathing, generally caused by common factors in modern life. OSA is most commonly associated with dysfunctions in the genioglossus (GG) muscles. In this study, we present the first version of a medical device that measures the electromyogram (EMG) of the GG. The prototype is composed of a (custom-made) 3D-printed mouthpiece. Impressions were taken for the lower arch and scanned with a lab scanner to be converted into digital impressions. ExoCad software was used to design the appliance. Fusion 360 software was then used to modify the design and create tubes to house the electrodes in a bilateral configuration to secure excellent and continuous contact with the GG muscle. Silver-silver chloride electrodes were incorporated within the appliance through the created tubes to record the muscle EMG. In this preliminary prototype, the EMG amplifier was placed outside the mouth, and isolated electric wires were connected to the amplifier input. Simple tests that included a group of OSA patients and a control group were done during wakefulness to check the comfort and stability of the device, understand the nature of GG EMG, and study which OSA might affect the daytime performance of the GG. The GG EMG was acquired from the participants for 60 seconds at Rest state when the participant rested his tongue without doing any activity. Then, the subject pushes his tongue against the fontal teeth with steady force while keeping the mouth closed (Active state). Several features were extracted from the acquired EMG: The results showed that mean power and standard deviation were higher in the control group than in the OSA group (p < 0.01). Regarding the wavelength during active state, the control group had a significantly longer wavelength than the OSA group (p < 0.01). Meanwhile, the mean frequency was higher in the OSA group (p < 0.01) at rest. Future research should focus on developing the device to be more user-friendly and easily used at home during wakefulness and sleep.

Most oral squamous cell carcinomas (OSCCs) arise from oral epithelial dysplasia; however, there is no useful marker for early OSCC detection, likely owing to the inability to continuously observe the carcinoma sequence. We aimed to establish an experimental model to observe changes in the sequential expression pattern of mRNA and protein in the same rat using liquid-based cytology techniques. Cytology specimens were collected from a 4-nitroquinoline 1-oxide-induced rat tongue cancer model at 2, 5, 8, 11, 14, 17, and 21 weeks. We examined candidate biomarker expression using immunocytochemistry and quantitative real-time PCR. The percentage of positively stained nuclei was calculated as the labeling index (LI). All rats had OSCC of the tongue at 21 weeks. Brd4 (Brd4), Myc (c-Myc), and Tp53 (p53) mRNA levels were upregulated during progression from negative for intraepithelial lesion or malignancy to SCC. Brd4- and c-Myc-LI were increased in low- and high-grade squamous intraepithelial lesions and SCC specimens. p53-LI was significantly increased in SCC specimens. Our experimental model allowed the observation of sequential morphological changes and mRNA and protein expression patterns in the same rat during carcinogenesis. By reducing the false negative rate, BRD4 and c-Myc can be useful markers for the early detection of OSCC.

Background: The absence of interdental papillae in dental prosthetics often results in unsatisfactory esthetic outcomes, such as black triangles and elongated clinical crowns. Although previous research has shown that gingival papillae can regenerate in a coronal direction, the mechanisms behind this phenomenon are not fully understood. Various theories have been proposed as potential explanations. Materials and Methods: This study evaluated several factors potentially influencing papilla growth, including adjacent elements, buc-cal-lingual papilla width, contact point position, convergent neck, crown overcontour, and intraoral negative pressure. A conceptual map was created to organize these factors, followed by their classification using a modified Overton Window. The principle of parsimony (Occam's Razor) was applied to identify the most plausible cause-related factors, categorizing them as causal relationship factors, filtered out factors, essential factors, or influencing factors. A mind map was used for visual grouping. Results: The analysis identified intraoral negative pressure as the most plausible cause-related factor for spontaneous papilla growth. Factors such as inflammation and drug-induced hyperplasia were excluded due to their association with unhealthy tissue. Other factors were classified as essential or influencing, but without direct causal links to papilla growth. Conclusions: Intraoral negative pressure is likely a key contributor to spontaneous papilla growth around implants. This finding, supported by abductive reasoning and the exclusion of less plausible factors, offers a new direction for enhancing esthetic outcomes in dental prosthetics, though further research is needed to confirm this causal relationship.

This work explores the significance of toothbrushing in maintaining optimal oral health, delving into its benefits, proper techniques, and types of toothbrushes. The primary cause of caries, periodontal diseases, and halitosis is oral biofilm development. One of the most fundamental practices in maintaining oral health is toothbrushing. Studies have confirmed that mechanical procedures for controlling plaque and toothbrushing, in particular, significantly decrease plaque accumulation. The significance of teeth brushing in preventing dental caries has been well-acknowledged for a considerable period. Dentists recommend brushing twice daily for at least two min to ensure thorough cleaning. Unfortunately, precise guidelines from dental associations are often missing. Authors mention that two min of brushing are insufficient for significant plaque removal; plaque removal increases with augmented brushing time, with maximum removal at 180 s. Multiple studies have documented that engaging in the practice of brushing one’s teeth twice a day has a preventive impact. Various toothbrush designs, including both manual and electric options, have been created to improve the elimination of dental biofilm and reduce the accumulation and persistence of bacteria. In conclusion, toothbrushing is a simple yet incredibly important practice for maintaining oral health. The benefits extend beyond just a bright smile, encompassing caries, gum disease, halitosis prevention, and the preservation of tooth enamel. Adhering to proper toothbrushing techniques, selecting the right toothbrush, and understanding the connection between oral health and overall well-being can lead to a healthier life. To foster favorable toothbrushing behaviors among the population, dental practitioners and public health experts must know the factors that influence toothbrushing habits.

Stage IV grade C localized periodontitis (pre-puberal localized aggressive periodontitis/LPP), an extremely rare form of periodontal disease, occurs in otherwise healthy individuals (no signs of dental plaque/calculus) due a hyper-aggressive auto-immune response to high periodontopathic bacteria levels. Methods: A 4-year-old Caucasian girl with unusual high mobility of temporary lower left canine and localized gingival inflammation was misrecognized by multiple clinicians (initially diagnosed with hypophosphatasia, genetic and metabolic disorders, all turning negative), over a period of 4-6 month, despite initial radiographs showing clear pathognomonic signs. LPP diagnostic was made by the last clinician, but by now the tooth was lost. Similar inflammation signs appeared around the lower temporary right canine. X-ray examination showed similar bone and periodontal loss as previously seen, while periodontopathic bacteria tested highly positive. The patient received both mechanical cleaning and ten days systemic antibiotic treatment (Augmentin and Metronidazole). Results: Two months after, inflammation signs disappeared, with periodontal regeneration radiologically present, and only small periodontopathic bacteria precursors concentrations. Conclusions: Despite initial periodontal loss, an adequate treatment can keep under control an LPP disease. Moreover, bone and periodontal regeneration appears if periodontopathic bacteria scores are kept lower, showing the importance of fast adequate diagnostic and treatment.

Background: Snus consumption is increasingly popular, mainly among the youth, due to the promotion of the tobacco industry and the lack of knowledge regarding its adverse effects. Even though some of its systemic complications are common knowledge, the oral consequences are rarely known. Aim: Therefore, the objective of this study is to evaluate the oral health effects of snus consumption among a highly exposed group of adolescent athletes. Design: Participants received an interactive presentation, followed by interviews and dental screenings by young doctors to establish trust. They were categorized into groups based on the frequency of snus usage. The oral hygiene habits and status, snus consumption habits and awareness about its adverse effects were evaluated. Results: Statistically significantly (p

Resection of malignant lesions in the oral and maxillofacial area causes functional and morphological defects. To recover from these defects, reconstruction surgery is needed such as a primary closure or a flap. There are advantages and disadvantages to the method of using the primary closure and the flap, and the choice of procedure is entirely up to a surgeon. The purpose of this study is to evaluate availability of primary closure in patients. For 10 years from January 2010 to May 2020, patients who recovered using flaps after removing malignant lesions from the oral cavity and those who closed the lesion using primary closure were investigated. The investigation was conducted by searching the database of the hospital. There were 85 patients who removed malignant lesions in the oral and maxillofacial area, and among them 16 patients closed the soft tissue defects using primary closure. Operation time, histologic types, stages, wound status, and period of hospitalization according to the patients' medical records were investigated retrospectively. Between the staging and the primary closure, statistically significant differences were observed between stage I and stage II patients in 13 patients using the primary closure. (P=0.046). Statistically significant differences were identified between operation time and primary closure, with an average of 4.02 hours (P=0.015). The average period of hospitality for patients who underwent primary closure was 13.4 days, compared to 26.7 days for those who underwent flap surgery. This difference was statistically significant (P=0.0003). This study evaluated the use of primary closure in patients who underwent resection of malignant lesions in the oral and maxillofacial area. Although the majority of patients underwent reconstruction with flaps, our results showed that primary closure can be a viable option for certain patients with early-stage lesions. Therefore, oral and maxillofacial surgeons should carefully consider various evaluation criteria and select appropriate reconstruction methods to optimize functional and aesthetic outcomes for each patient.

Alzheimer’s disease (AD) and the therapies of AD with anti-amyloid1-42 (Aβ) monoclonal antibodies are associated with the vascular complications of brain edema, hemorrhage, and cerebral amyloid angiopathy (CAA) termed amyloid-related imaging abnormalities (ARIAs). The neuropathology of normal and AD brains demonstrates that monocyte/macrophages (MMs) are critical in successful brain clearance in healthy brain by up-loading, transporting, and degrading Aβ but fail degradation and clearance in AD patients by releasing Aβ into vessels at the blood-brain barrier, causing vasculitis and ARIAs. The naturally-formed epoxides (EpFAs) of polyunsaturated fatty acids (PUFA’s), including arachidonic, docosahexaenoic, and eicosapentaenoic fatty acids, may repair degradation of Aβ by regulating Aβ-degrading enzymes, inflammatory cytokines, and unfolded protein response (UPR) to endoplasmic reticulum stress in a homeostatic fashion. EpFAs are, however, degraded by the soluble epoxide hydrolase enzyme (sEH) but are protected by the sEH inhibitor (sEHI) TPPU. In the cultures of AD patients’ macrophages, TPPU with the epoxide EEQ, and the cGAS/STING inhibitor H-151 increased uptake of Aβ at 2 hours and degradation of Aβ at 24 hours. In conclusion, the soluble epoxide hydrolase inhibitor TPPU with omega-3 fatty acids and the cGAS/STING inhibitor H-151 increase Aβ uptake and degradation in macrophages of AD patients, and potentially enhancing Aβ clearance in the AD brain.

The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is a suitable environment that provides various kinds of biological niches such as teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome plays an important role in triggering, development, and progression of oral and systemic diseases. Currently, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology, and is overwhelmingly promising compared to the previous era. It has been found that patients with oral diseases and systemic diseases have variations in the oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that oral microbiome plays in influencing oral and systemic diseases, and updates the knowledge related to the oral microbiome over the past 30 years. A wide range of updates was provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and help develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics.

Incidental findings (IFs) depicted in imaging tests during diagnostic evaluation of patients with cleft lip and/or palate (CL/P) can guide clinicians during treatment-planning procedures for effective, comprehensive cleft care. Evidence regarding IFs in different anatomical regions distant from the dentition are scarce. The aim of this study was to compare the prevalence of IFs in various anatomical areas between patients with non-syndromic CL/P and unaffected subjects. Orthopantomographs (OPT), lateral cephalometric (LC) radiographs and cone-beam computed tomography (CBCT) scans of 120 subjects (case group: n = 40, 18 females, age 14.5 ± 5.0 years; control group: n = 80, 36 females, age 14.6 ± 4.9 years) were examined and IFs were assessed by four observers. Significantly higher prevalence of IFs (p &lt; 0.001) was reported in the case group (97.5%) compared with the control group (62.5%). The most prevalent location of IFs in the case group was the maxilla (92.5%), followed by the nasal cavity (75.8%) and the mandible (63.2%), while in the control group, the highest rates of IFs occurred in the maxilla (43.8%), mandible (41.3%) and temporomandibular joint (TMJ) (14.7%). No gender-dependent pattern for IF occurrence was detected overall. Orofacial clefts may affect the mandible. However, the reported IFs were limited compared to those in the maxilla. In conclusion, individuals with CL/P are more likely to present with a range of IFs than their unaffected peers. Understanding the association between CL/P and IFs is critical for successful interdisciplinary treatment, raising awareness of the potential need for future dental care for cleft patients, and managing extra-dental aberrations. A systematic assessment of diagnostic records is required to eliminate the risk of overlooking clinically significant IFs.

Objective. The present study examined the potential use of computed tomography panoramic mandibular indices on cone beam CT (CBCT) for the assessment of bone density in postmenopausal women with low bone mass. Study design. We enrolled 104 postmenopausal women who performed dual energy X-ray absorptiometry (DXA) using a DXA scanner and mental foramen region CBCT using NewTom VGi EVO Cone Beam 3D system. We assessed the relationship between DXA parameters: lumbar, femoral neck and total hip T score, bone mineral density (BMD), and lumbar trabecular bone score (TBS) and the panoramic mandibular indices: computed tomography mandibular index superior (CTI(S)), computed tomography mandibular index inferior (CTI(I)) and computed tomography mental index (CTMI). Results. We found important correlations between the CTI(I), CTI(S) and CTMI and bone mass, quantitative evaluated as BMD and T-score and also quality using TBS score. Conclusion. CBCT measured indices CTI(S), CTI(I), CTMI are useful in assessing patients with low bone mass.

Background Patients with severe dysphagia are usually fed using a nasogastric tube (NGT). Many patients who receive long-term NGT feeding are unable to obtain sufficient nutrients orally immediately after NGT removal. Thus, a transitional period involving oral diet training is required to transition from NGT feeding to exclusive oral feeding. We aimed to investigate the therapeutic effect of oral diet training in indwelling NGT patients with prolonged dysphagia. Methods A total of 175 patients who were fed using an NGT for more than 4 weeks were enrolled. Their swallowing function was evaluated by a videofluoroscopic swallowing study (VFSS). During the VFSS, patients received thick and thin barium while the NGT was insulted. Then, the patients underwent a VFSS without an NGT thirty minutes after NGT removal. If a patient had no aspiration with NGT inserted during the VFSS, oral diet training combined with NGT feeding was recommended. Results Of the 49 indwelling NGT patients who were recommended to receive oral diet training, 39 (79.6%) transitioned to exclusive oral feeding. A transition period of 2-8 weeks was required for them to achieve full oral feeding. Patients who were eligible for oral feeding trials showed no significant aspiration during the VFSS with an NGT inserted and had sufficient cough function. Patients who required prolonged NGT feeding and who could not complete oral trials showed significant aspiration during the VFSS when an NGT was inserted. Conclusion This study demonstrated that oral diet training combined with NGT feeding was safe in patients with prolonged dysphagia who had sufficient cough function and no aspiration during VFSS. We suggest that if the patient is a proper candidate for NGT removal, direct oral feeding training with an NGT inserted could be a useful therapeutic strategy during the transitional period from long-term NGT feeding to successful oral feeding.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

This critical review revisited the new classification system for periodontitis, specifically for staging, suggesting modifications, and introducing a new flowchart for a better clinical evaluation. It evaluated articles published between 2018 and 2024 in the English language, which had an educational motivation focused on staging periodontitis. PubMed/MEDLINE, Web of Science, and Embase databases were used to retrieve the articles. The focus questions involved the analysis of all parameters for staging periodontitis. A total of 836 articles were initially found; 388 duplicated were excluded; 448 were evaluated by title and abstract; 26 articles followed for full-text reading, and 6 articles were included in this critical review (k=0.98). All articles included detailed parameters and steps about how to diagnose periodontitis. Therefore, it was possible to observe instability and “gray zones” in the staging step, which was due to a lack of priority and an organized order sequence. This review suggests the severity parameters cannot be overcome by complexity parameters, following a cumulative sequence: CAL (1^st), RBL (2^nd), TLP (3^rd), and, after, complexity parameters. An exception must be permitted only for complexity factors between Stages III and IV that can change the initial Stage (III or IV) obtained through the severity analysis, but only between themselves. Moreover, for patients without tooth loss or with TLP of ≤4 teeth (without need for complex rehabilitation) and presenting any type of drifting or flaring or a secondary traumatic occlusion, it cannot be a justification for moving the diagnosis from Stage III to Stage IV.

Background Gingivitis can develop without mechanical cleaning within three weeks. The first clinical sign is bleeding on positive probing. The accumulation of dental biofilm generates an inflammatory gingival response. In the past decade, attention has focused mainly on the interproximal areas and the use of customsized interproximal toothbrushes.The aim of the study was to evaluate the effectiveness of individualized oral hygiene education and its role in dental prevention among patients with dental problems. Methods Before treatment, patients were clinically and radiologically examined, full mouth plaque score (FMPS), full mouth bleeding score (FMBS), and bleeding on brushing (BOB) were recorded, and matrix-metalloproteinase-8 (MMP-8) was measured by using a chair-side MMP-8 measuring system. Patients in group A had gingivitis, but no periodontal damage and patients in group B had periodontal damage. Patients in both groups A and B were identified in to four subgroups based on their toothbrushing habits and the oral health education they received. The three months after initial examination, each patient was examined three more times (2, 4 and 12 weeks later). Results It was concluded that subjects in groups A1 and B1 showed significant reduction in BOB, MMP-8, FMBS and FMPS levels after two weeks. Solo Prophylaxis (A1and B1) remained as a well-constructed protocol with hte complete resolution of interdental inflammation after two weeks. Other subgroups achieved significant reductions only after 12 weeks. Conclusions BOB and MMP-8 are valuable complements in preventive dentistry, and are able to detect potential pathological processes in interproximal spaces. The clinical relevance of BOB, in addition to FMBS, FMPS and gingival inflammation can be demonstrated to patients, which may increase compliance.

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.

Objective: This study aimed to assess the impact of artificial intelligence (AI)-driven noise reduction algorithms on metal artifacts and image quality parameters in cone-beam computed tomography (CBCT) images of the oral cavity. Materials and Methods: This retrospective study included 70 patients, 61 of whom were analyzed after excluding those with severe motion artifacts. CBCT scans, performed using a Hyperion X9 PRO 13 × 10 CBCT machine, included images with dental implants, amalgam fillings, orthodontic appliances, root canal fillings, and crowns. Images were processed with ClariCT. AI deep learning model (DLM) for noise reduction. Objective image quality was assessed using metrics such as the differentiation between voxel values (ΔVVs), the artifact index (AIx), and the contrast-to-noise ratio (CNR). Subjective assessments were performed by two experienced readers, who rated overall image quality and artifact intensity on predefined scales. Results: Compared with native images, DLM reconstructions significantly reduced the AIx and increased the CNR (p<0.001), indicating improved image clarity and artifact reduction. Subjective assessments also favored DLM images, with higher ratings for overall image quality and lower artifact intensity (p<0.001). However, the ΔVV values were similar between the native and DLM images, indicating that while the DLM reduced noise, it maintained the overall density distribution. Orthodontic appliances produced the most pronounced artifacts, while implants generated the least. Conclusion: AI-based noise reduction using ClariCT. AI significantly enhances CBCT image quality by reducing noise and metal artifacts, thereby improving diagnostic accuracy and treatment planning. Further research with larger, multicenter cohorts is recommended to validate these findings.

Surgical simulators are crucial in early craniofacial and plastic surgical training, necessitating synthetic materials that accurately replicate tissue properties. Recent critiques of our lab’s currently deployed silicone surrogate have highlighted numerous areas for improvement. To further refine our models, our group's objective is to find a composition of materials that is closest in fidelity to native oral mucosa during surgical rehearsal by expert craniofacial surgeons. Fifteen platinum silicone-based surrogate samples were constructed with variable hardness and slacker percentages. These samples underwent evaluation of tactile sensation, hardness, needle puncture, cut resistance, suture retention, defect repair, and tensile elasticity. Expert craniofacial surgeon evaluators provided focused qualitative feedback on selected top-performing samples for further assessment and statistical comparisons. Evaluation revealed surrogate characteristics with satisfactory to good performance. Sample 977 exhibited the highest performance, and comparison with the original surrogate (sample 810) demonstrated significant improvements in critical areas, emphasizing the efficacy of the refined composition. The study identified a silicone composition that directly addresses the feedback received by our team’s original silicone surrogate. The study underscores the delicate balance between biofidelity and practicality in surgical simulation. The need for ongoing refinement in surrogate materials is evident to optimize training experiences for early surgical learners.

Surgical simulators are crucial in early craniofacial and plastic surgical training, necessitating synthetic materials that accurately replicate tissue properties. Recent critiques of our lab’s currently deployed silicone surrogate have highlighted numerous areas for improvement. To further refine our models, our group's objective is to find a composition of materials that is closest in fidelity to native oral mucosa during surgical rehearsal by expert craniofacial surgeons. Fifteen platinum silicone-based surrogate samples were constructed with variable hardness and slacker percentages. These samples underwent evaluation of tactile sensation, hardness, needle puncture, cut resistance, suture retention, defect repair, and tensile elasticity. Expert craniofacial surgeon evaluators provided focused qualitative feedback on selected top-performing samples for further assessment and statistical comparisons. Evaluation revealed surrogate characteristics with satisfactory to good performance. Sample 977 exhibited the highest performance, and comparison with the original surrogate (sample 810) demonstrated significant improvements in critical areas, emphasizing the efficacy of the refined composition. The study identified a silicone composition that directly addresses the feedback received by our team’s original silicone surrogate. The study underscores the delicate balance between biofidelity and practicality in surgical simulation. The need for ongoing refinement in surrogate materials is evident to optimize training experiences for early surgical learners.

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.

Purpose of review: This review investigates the oral microbiome's composition, functions, influencing factors, connections to oral and systemic diseases, and personalised oral care strategies. Recent findings: The oral microbiome is a complex ecosystem consisting of bacteria, fungi, archaea, and viruses that contribute to oral health. Various factors, such as diet, smoking, alcohol consumption, lifestyle choices, and medical conditions, can affect the balance of the oral microbiome and lead to dysbiosis, which can result in oral health issues like dental caries, gingivitis, periodontitis, oral candidiasis, and halitosis. Importantly, our review explores novel associations between the oral microbiome and systemic diseases including gastrointestinal, cardiovascular, endocrinal, neurological conditions, autoimmune diseases, and cancer. We comprehensively review the efficacy of interventions like dental probiotics, xylitol, oral rinses, fluoride, essential oils, oil pulling, and peptides in promoting oral health by modulating the oral microbiome. Summary: This review emphasizes the critical functions of the oral microbiota in dental and overall health, providing insights into the effects of microbial imbalances on various diseases. It underlines the significant connection between the oral microbiota and general health. Furthermore, it explores the advantages of probiotics and other dental care ingredients in promoting oral health and addressing common oral issues, offering a comprehensive strategy for personalized oral care.

The management of erectile dysfunction (ED) shows several grey zones, especially in terms of patient satisfaction and adherence to the treatment. The main and first-line treatment for ED is drug therapy, mainly phosphodiesterase-5 inhibitors (PDE-5is) but the adherence to the therapy is not optimal due to the low patient satisfaction reported in several cases. To address this issue, different administration routes and PDE-5is pharmacological formulations have been introduced in the pharmacological market. The pharmaceutical market has recently seen the introduction of a novel sildenafil oral suspension. This device offers access to all therapeutic regimens in one device, releasing 0.5 mL of suspension containing 12.5 mg of sildenafil with each pulse. This formulation enables tailored dosing based on clinical requirements and the demands of ED patients. Here, we aim to give a brief narrative review of the management of this new oral suspension in order to provide the readers with some suggestions to use in everyday clinical practice, on the basis of the recent evidence, by using an easy and rapid-to-consult questions and answers form. Also included are the conclusions of a board meeting of experienced andrologists regarding the most recent developments in this area.

In this study, we aimed to explore the oral bacteria and fungi that can help discern oral squamous cell carcinoma (OSCC) and investigate the correlations between multiple key pathogens. Methods: Twelve participants (8 females and 4 males; mean age, 54.33 ± 20.65 years) were prospectively recruited into three groups: Group 1: healthy control, Group 2: patients with stomatitis, and Group 3: patients with OSCC, with 4 individuals in each group. Unstimulated whole saliva samples from these participants were analyzed using real-time PCR to assess the presence and abundance of 14 major oral bacterial species and Candida albicans. Results: The analysis revealed significant differences for certain microorganisms, namely Treponema denticola (T. denticola), Lactobacillus casei (L. casei), and Candida albicans. T. denticola was most abundant in the OSCC group (5,358,692.95 ± 3,540,767.33), compared to the stomatitis (123,355.54 ± 197,490.86) and healthy control (9,999.21 ± 11,998.40) groups. L. casei was undetectable in the healthy control group, but was significantly more abundant in the stomatitis group (1,653.94 ± 2,981.98) and even higher in the OSCC group (21,336.95 ± 9,258.79) (p = 0.001). A similar trend was observed for C. albicans, with DNA copy numbers rising from the healthy control (464.29 ± 716.76) to the stomatitis (1,861.30 ± 1,206.15) to the OSCC group (9,347.98 ± 5,128.54) (p = 0.006). The amount of T. denticola was positively correlated with L. casei (r=0.890, p<0.001) and C. albicans (r=0.724, p=0.008). L. casei's DNA copy number was strongly correlated with C. albicans (r=0.931, p<0.001). These three oral microbes exhibited strong positive correlations with each other and had various direct or indirect relationships with other species. Conclusions: In the OSCC group, T. denticola, L. casei, and C. albicans exhibited strong positive correlations with one another, further emphasizing the need for a deeper understanding of the complex microbial interactions in the OSCC environment.

Studies on the possible association between bacteria and oral squamous cell carcinoma (OSCC) remain inconclusive, largely due to methodological variations/limitations. The objective of this study was to characterize the species composition as well as functional attributes of the bacteriome associated with OSCC. DNA obtained from 20 fresh OSCC biopsies (cases) and 20 deep-epithelium swabs (matched control subjects) were sequenced for the V1-V3 region using Illumina’s 2x300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a prioritized BLASTN-algorithm. Downstream analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum subsp. polymorphum was the most significantly overrepresented species in the tumors followed by Pseudomonas aeruginosa and Campylobacter sp. Oral taxon 44, while Streptococcus mitis, Rothia mucilaginosa and Haemophilus parainfluenzae were the most significantly abundant in the controls. Functionally, genes involved in bacterial mobility, flagellar assembly, bacterial chemotaxis and LPS synthesis were enriched in the tumors while those responsible for DNA repair and combination, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, ribosome biogenesis and glycolysis/gluconeogenesis were significantly associated with the controls. This is the first epidemiological evidence for association of F. nucleatum and P. aeruginosa with OSCC. Functionally, an “inflammatory bacteriome” is enriched in OSSC.

Objectives: The goal of this pilot study was to validate and introduce a new AI tool (algorithm), providing and comparing (1) the periodontal/peri-implant diagnosis between professional (specialist) and automated tool, (2) risk assessment and prognostication with the algorithm, and (3) establish cut-off limits for clinically significant disease with a new score system (GF-PeDRA score). Methods: All patients were evaluated by two evaluators, and in case of any divergence, the case was revisited and discussed until clarification and definition. The validation sample constituted 221 patients. The AI tool (GF-PeDRA©) had eighteen parameters to be assessed, involving systemic and local predictors, achieving an octadecagon (an eighteen-sided polygon). The parameters were: (1) The highest probing depth (PD); (2) Number of interproximal sites with bone loss; (3) The highest clinical attachment loss (CAL); (4) Maximum radiographic bone loss (RBL); (5) Bleeding on probing (% BoP); (6) Bone loss pattern; (7) Tooth loss including periodontally hopeless teeth planned for extraction; (8) Evidence of progression over five years; (9) Need for complex rehabilitation; (10) Patient’s age; (11) CAL and biofilm accumulation; (12) Smoking; (13) Diabetes; (14) Extension and distribution of the disease; (15) Peri-implant disease; (16) Other systemic conditions (other than diabetes); (17) Furcation involvement; and (18) Necrotizing lesion. A new score system (GF-PeDRA© score) based on the percentual of the octadecagon area is obtained; if the area was ≥0% to ≤9%, the prognosis is good; ≥10% and ≤ 24%, it is fair; ≥25% and ≤37%, poor; ≥38% and ≤49%, it is questionable; and between ≥50% to ≤100%, the prognosis is hopeless. Results: 221 patients were enrolled, with a mean age of 46.73. 5301 teeth were examined. 187 non-smokers (84.62%) and 34 smokers (15.38%) were included. 193 (87.33%) patients did not have diabetes, whereas 28 (12.67%) had. Comparing the diagnosis between both evaluators, k=0.83; all disagreed cases were re-discussed, and a final decision/diagnosis was reached. After this, the diagnosis found was contrasted with the diagnosis achieved by GF-PeDRA© and a perfect agreement was observed, 100% (k=1.0). 28 patients were diagnosed as periodontally healthy, 55 with plaque-induced gingivitis, and 138 with periodontitis. Only one case of molar/incisor pattern was observed. No peri-implant disease or necrotizing condition was found. The mean CAL found was 3.19 mm; 25 patients (11.31%) had a furcation involvement. The mean percentual of BoP found was 28.67% (median = 19%; maximum: 100%; minimum: 100%); and the mean PD was 5.31 mm. The mean of the new GF-PeDRA© score (ranging from 0% to 100%) was 28.64%, with a median of 32.2% (minimum: 0.6% and maximum: 64.1%). Then, analyzing the GF-PeDRA© score of 221 patients enrolled, 48 (21.73%) were sorted as a Good prognosis for periodontal treatment, 43 (19.45%) had a Fair prognosis, 43 (19.45%) had a Poor prognosis, 68 (30.77%) had a Questionable prognosis, and 19 (8.60%) had a Hopeless prognosis. Conclusion: The new AI tool (GF-PeDRA©) was validated and proved to be extremely helpful in diagnosing and providing risk assessment and prognosis.

The oral microbiome, studied by sampling the saliva or oral rinse, has been long thought to have diagnostic capacity for head and neck cancers (HNC). However, previous reports on the HNC oral microbiome provide inconsistent results. The aim of this study is to consolidate these datasets and determine the oral microbial composition between HNC patients to healthy and premalignant individuals. We analyzed 16 published head and neck cancer (HNC) short-read 16S rRNA sequencing datasets, specifically targeting the V3V4, V4 and V4V5 regions. These datasets included saliva and oral rinse samples from donors with HNC, as well as from healthy and premalignant donors. Differences in diversities and microbial abundance were determined. HNC saliva displayed lower alpha diversity than healthy donors. In contrast, the opposite trend was observed for oral rinse samples. Beta diversity were largely similar across different patient types. Similar oral phyla were detected for all samples, but proportions were largely dependent on sample type (i.e. saliva or oral rinse) and primer set utilised for 16S rRNA sequencing. Neisseria, Leptotrichia and Megasphaera were elevated in healthy saliva, while Mycoplasma was elevated in HNC saliva. Oral rinse and saliva displayed similar enrichment for Fusobacterium, while Veillonella, Alloprevotella, and Campylobacter had conflicting results. The sparse partial least squares discriminant analysis model performed effectively in discriminating HNC from healthy or premalignant patients using V3V4 saliva (AUC = 0.888), and V3V4 oral rinse (AUC = 0.928), while poor discriminative capacity was observed for V4 saliva (AUC = 0.688). In conclusion, our meta-analysis highlighted the limitations of 16S rRNA sequencing, particularly due to variations across study batches, primer sets (i.e. V3V4, V4), and sample types. Hence, caution should be exercised when interpreting 16S rRNA sequencing results across studies, especially when different primer sets and sample types are used.

Vegetative desiccation tolerance has evolved within the genus Craterostigma and Lindernia. A centre of endemism and diversification for these plants appears to occur in ancient tropical montane rainforests of east Africa in Kenya and Tanzania. Lindernia subracemosa, a desiccation-sensitive relative of C. plantagineum, occurs in these rainforests and experiences adequate rainfall and thus does not require desiccation tolerance. However, sharing this inselberg habitat, another species Lindernia brevidens does retain vegetative desiccation tolerance and is also related to the resurrection plant C. plantagineum found in South Africa. Leaf material was collected from all three species at different stages of hydration: fully hydrated, half-dry (ca. 45% relative water content), and fully desiccated. Cell wall monosaccharide datasets were collected from all three species. Comprehensive microarray polymer profiling (CoMPP) was performed using ca. 27 plant cell wall specific antibody and carbohydrate binding module probes. Global datasets do not show significant differences between the selected species suggesting that cell wall modifications in response to vegetative desiccation involve subtle cell wall remodelling not reflected by compositional analysis and that the plants and their walls are constitutively protected against desiccation.

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.

In order to tackle the issue of severe rocking phenomenon under seismic conditions in structures equipped with steel spring isolation bearings, this paper investigates a novel type of anti-rocking bearing. Firstly, the structural configuration and working principle of the novel anti-rocking bearing are introduced, and a design method for bearing parameters is proposed. Secondly, a finite element analysis model is established using SAP2000 software to conduct nonlinear dynamic time history analysis under seismic loading. The analysis results show that the structural arrangement of the novel anti-rocking bearing reduces both the vertical displacement difference and the rocking angle of the isolation layer. The bearing exhibits a certain level of anti-rocking effect, but it may cause significant tensile forces in some bearings, necessitating the installation of anti-tensile reinforcement. The effectiveness of the anti-rocking effect improves as the stiffness of the steel tension rod in the bearing increases; however, it also leads to higher maximum tension in individual bearings as well as the total tension in all bearings. For structures equipped with the novel anti-rocking bearing, the acceleration amplifies under most cases, with amplification coefficients ranging from 0.82 to 1.55. The performance of the novel anti-rocking bearing varies significantly for different seismic waves. The stiffness of the steel tension rod should be determined considering the reference pressure of the bearing and the maximum designed tension of the bearing. Through the finite element simulation of the bearing, the mechanical properties of the bearing are basically the same as the theoretical analysis results. For the cylinder and the joint bearing, certain structural measures need to be taken to ensure its strength and stiffness.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of fenretinide, a synthetic retinoid chemically related to all-trans-retinoic acid, after administration of a novel oral nanoformulation of fenretinide, called bionanofenretinide (BNF). BNF was developed to overcome the major limitation of fenretinide: its poor aqueous solubility and bioavailability due to its hydrophobic nature. The method proved to be reproducible, precise, and highly accurate for the measurement of the drug and the mains metabolites. The lower limit of quantification resulted 1 ng/mL. The curve range of 1-500 ng/mL and 50-2000 ng/mL, for plasma and tumor homogenate respectively, was appropriate for the analysis, as demonstrated by the accuracy between 96.8% and 102.4% for plasma and 96.6-102.3% for tumor. The inter-days precision and accuracy determined on quality controls at 3 different levels were in ranges of 6.9%-7.5% and 99.3-101.0% and 0.96-1.91% and 102.3-105.8% for plasma and tumour, respectively.

This research addresses a gap in the literature by conducting a comprehensive analysis of patients’ level of satisfaction with dental care. Methods: By combining quantitative and qualitative survey methods with the PSQ questionnaire this study aims to augment ongoing initiatives to enhance dental patients’ experiences by painting a more comprehensive depiction of patients' level of satisfaction; Results: When asked about their overall level of satisfaction 77,1% of the patients said they received excellent services from the office personnel and 72,2% said they trust their doctors; Conclusions: Assessing patient satisfaction in the realm of dental services quality is crucial for enhancing service quality and accuracy, benefiting both patients and dentists, and ultimately improving public health.

Achieving effective haemostasis is crucial for successful outcomes and optimal patient care in contemporary oral surgery. Control of bleeding is essential in procedures like extractions, implant placements, periodontal surgeries, and soft tissue interventions. Efficient management ensures a clear surgical field, reduces post-operative complications, and promotes healing. Local haemostatic agents are essential tools for oral surgeons, offering targeted and controlled methods to achieve haemostasis. These agents include diverse materials and technologies, each with unique mechanisms of action suited to specific surgical scenarios. This review explores the spectrum of local haemostatic agents in contemporary oral surgery, focusing on their efficacy, safety, and practical utility. By examining the characteristics and clinical performance of various haemostatic agents, this review provides valuable insights to guide dentists and oral surgeons in selecting the most appropriate agent for specific situations. A literature search in electronic databases such as Medscape, PubMed-Medline, Science Direct, and EBSCO Host identified 46 publications from 1990 to 2023. This comprehensive examination aims to enhance understanding of local haemostatic agents and their role in advancing the standards of care in contemporary oral surgery.

Cluster of differentiation 44 (CD44) has been investigated as a cancer stem cell (CSC) marker, and plays critical roles in tumor malignant progression. The splicing variants are overexpressed in many carcinomas, especially squamous cell carcinomas, and play critical roles in the promotion of tumor metastasis, the acquisition of CSC properties, and resistance to treatments. Therefore, each CD44 variant (CD44v) function and distribution in carcinomas should be clarified for the establishment of novel tumor diagnosis and therapy. In this study, we immunized mice with a CD44 variant (CD44v3−10) ectodomain and established various anti-CD44 monoclonal antibodies (mAbs). One of the established clones (C44Mab-34; IgG1, kappa) recognized a peptide which covers both variant 7 and 8-encoded region, indicating that C44Mab-34 is a specific mAb for CD44v7/8. Moreover, C44Mab-34 reacted with CD44v3–10-overexpressed Chinese hamster ovary-K1 (CHO) cells or oral squamous cell carcinoma (OSCC) cell line (HSC-3) by flow cytometry. The apparent KD of C44Mab-34 for CHO/CD44v3–10 and HSC-3 was 1.4 × 10−9 M and 3.2 × 10−9 M, respectively. C44Mab-34 could detect CD44v3–10 in western blotting, and stained the formalin-fixed paraffin-embedded OSCC in immunohistochemistry. These results indicate that C44Mab-34 is useful for detecting CD44v7/8 in various applications, and expected for the application of OSCC diagnosis and therapy.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

The paper describes the new method for image compression based on coordinated group signal transformation. The algorithm is a type of difference coding. Coordinated processing significantly simplifies the difference signal conversion scheme using a single group codec for all signals. The described method considers color channels as correlated signals of a multi-channel communication system. The specifics of the processed data required modification of the coordinated group processing algorithm. First, we changed how to calculate the difference signals to prevent data loss. Secondly, the group codec was supplemented with a neural network to improve the quality of reconstructed images. We considered the following types of neural networks: fully connected, recurrent, convolution, and convolution in the Fourier space. Based on the simulation results, it is best to use fully connected neural networks if the goal is to minimize processing delay time. These networks have a response time of 13 ms. On the other hand, if the priority is to improve quality in cases where delays are not critical, then convolution neural networks in the Fourier space should be used. These networks have a response time of 140 ms and are of significant interest.

The oral cavity harbors hundreds of microbial species that are present either as planktonic cells, or incorporated into biofilms. The majority of the oral microbes are commensal organisms. Those that are pathogenic microbes can result in oral infections, and at times initiate systemic diseases. Biofilms that contain pathogens have been challenging to control. Many conventional antimicrobials have proven to be ineffective. Recent advances in science and technology are providing new approaches for pathogen control and containment and methods to characterize biofilms. This perspective provides: 1) A general understanding of biofilm development; 2) A description of emerging chemical and biological methods to control oral biofilms; 3) An overview of high-throughput analytical approaches to analyze biofilms.

This review paper focuses on the joint toxicity and interaction of carbon-based nanomaterials (CNMs) with co-existing pollutants in aquatic environments. It explores the potential harmful effects of chemical mixtures on living organisms, emphasizing the importance of scientific mod-eling to predict mixed toxic effects. The study involved a systematic literature review to gather information on the joint toxicity and interaction between CNMs and various co-contaminants in aquatic settings. A total of 53 publications were chosen and analyzed, categorizing the studies based on the tested CNMs, types of co-contaminants, and the used species. Common test models included fish and microalgae, with zebrafish being the most studied species. The review under-scores the necessity of conducting mixture toxicity testing to assess whether the combined effects of CNMs and co-existing pollutants are additive, synergistic, or antagonistic. The development of in silico models based on the solid foundation of research data represents the best opportunity for joint toxicity prediction, eliminating the need in a great quantity of experimental studies.

Background: Research articles are essential for describing new ideas, techniques, and procedures and consolidating concepts. It creates an opportunity to expose studies and publicly assimilate published knowledge. Therefore, one of them is the most used and accepted index to verify the author’s scientific impact is the H-index or Hirsch index. It provides a robust single metric that combines quality and quantity. Therefore, it presents disadvantages, (1) researchers with shorter scientific carriers may have fewer articles and citations than those with longer scientific life; (2) it allows scientists to receive citations even if no new papers are published; (3) it is only useful for comparing the better scientists in a field; (4) this indicator can never decrease; (5) it is only weakly sensitive to the number of citations received; (6) the major and minor (or no) contributor in the research gained equal h-index. Then, the H-index ignores the total of citations and the time of a researcher's experience (“scientific age” [sa]). Objective: Thus, the goal of this study was to present a new index system (GFsa index ©) based on the two variables completely forgotten (total of citations and “scientific age”), introducing a new terminology “scientific age”, to evaluate the best-ranked researchers in Dentistry. Methods: The AD Scientific Index was used, and all researchers included in this study were cited in the AD Scientific Index (2024) in the Dentistry field and had the Google Scholar page accessible for a consultation to manually obtain the total of citations and calculate the “scientific age”. The information was retrieved by two authors (G.V.O.F. and J.C.H.F.), who assessed the data twice to avoid errors or mistakes. For inclusion: a minimum H-index value of 30; for exclusion: (i) the author did not have a Google Scholar page; (ii) duplicated author; or (iii) presented any suspicious activities about manipulation of articles. Then, a dataset of all researchers who were reported in Dentistry was prepared (name, H-index, i10 index, and publications). The formula developed and applied was GFsa=(total number of citations)/(“scientific age)². The Pearson correlation statistically evaluated the data obtained; the confidence interval was 95%. Results: A total of 9,093 researchers in Dentistry were recorded, of whom 1,020 were included. Then, we collected all 1,020 researchers' Google Scholar data (publications, citations, and indexes), and each researcher's total citations and “scientific age” were registered and calculated. The mean “scientific age” registered was 34.18 ± 13.34 (standard error of mean = 0.4181). With this information and data collected, GFsa index © was calculated, presenting a minimum value of 0.2186 and a maximum of 154.8 (mean = 10.33 ± 11.82; standard error of mean = 0.3706). Then, the data was organized and sorted following the ranking obtained in the GFsa index ©. The Pearson correlation showed that the H-index had a weakly positive association with the researcher’s “scientific age”; this fact means that the H-index will increase according to the “scientific age” increase. Otherwise, a moderately negative correlation between GFsa and “scientific age” was demonstrated, whereby a higher GFsa © had a lower “Scientific age”. This assessment shows that the variables introduced were fairly used. Moreover, a positive correlation was observed between both indexes (H-index and GFsa). Conclusion: It is possible to conclude that the new variable reported (“Scientific age”) and using the total citations brought a fairer and more feasible evaluation among the researchers. Thus, we are launching the new GFsa index © and the new information named “Scientific age” for the first time in the literature. The future perspective of the GFsa © application will be (1) the evaluation of the 9,093 researchers in Dentistry (total initially registered), including more authors/researchers in the Dentistry field, (2) expanding the exposition of this new index for other areas of the knowledge, and (3) provide free access of all data through the website (http://gfindex.us.to).

The real systems are often complex, nonlinear, and noisy in various areas including mathematics, natural science, and social science. We present the symplectic entropy (SymEn) measure as well as an analysis method based on SymEn to estimate the nonlinearity of the complex system by analyzing the given time series. The SymEn estimation is a kind of entropy based on symplectic principal component analysis (SPCA) which represent organized but unpredictable behaviors of systems. The key to SPCA is to preserve the global submanifold geometrical properties of the systems through symplectic transform in the phase space, which is a kind of the measure-preserving transforms. The capability of preserving the global geometrical characteristics makes the SymEn a test statistic to detect the nonlinear characteristics in several typical chaotic time series and the stochastic characteristic in the Gaussian white noise. The results are in agreement with findings in the approximate entropy (ApEn), the sample entropy (SampEn) and the fuzzy entropy (FuzzyEn). Moreover, the SymEn method is also used to analyze the nonlinearities of the real signals (including the EEG signals for ASD and healthy subjects, and the sound and vibration signals for the mechanical systems). The results indicate that the SymEn estimation can be taken as a measure for describing the nonlinear characteristics in the data collected from the natural complex systems.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by &gt;6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Backgroud. To improve mortality in patients with sepsis and septic shock, anticoagulant and acute blood purification therapies are performed depends on their severity of organ failure including coagulopathy. Therapeutic approach is required in clinical settings. Material and Methods. We evaluated anticoagulant and acute blood purification therapy in 2,007 patients with sepsis-induced disseminated intravascular coagulation (DIC) in a post-marketing survey examining plasma-derived antithrombin (AT) concentrate. Results. The 28-day mortality rate was 24.2%; before AT administration, there was a significant difference in proportion to the severity of the Sequential Organ Failure Assessment (SOFA) score (p<0.001). The median SOFA score was 9. In patients with SOFA scores >9, the mortality rate was lower in AT combined therapy with recombinant thrombomodulin (rTM) than in AT monotherapy if their JAAM DIC score was >6 (28.5% and 40.0%, respectively; p =0.031). In multiple logistic regression analysis, endotoxin adsorbed polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) before AT administration was correlated with reduced 28-day mortality (odds ratios: 2.071; 95% confidence intervals 1.374–3.121, p=0.001). Conclusions. To improve mortality in patients with sepsis, if patients with endotoxin-induced septic shock, PMX-DHP would undergo, and further development to DIC, AT concentrate administer, followed by rTM if their SOFA and JAAM DIC scores are >9 and 6, respectively. Further prospective study is needed.