Improving Lung Cancer Screening Selection: The HUNT Lung Cancer Risk Model for Ever-Smokers Versus the NELSON and 2021 United States Preventive Services Task Force Criteria in the Cohort of Norway: A Population-Based Prospective Study.

Background: Improving the method for selecting participants for lung cancer (LC) screening is an urgent need. Here, we compared the performance of the Helseundersøkelsen i Nord-Trøndelag (HUNT) Lung Cancer Model (HUNT LCM) versus the Dutch-Belgian lung cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON)) and 2021 United States Preventive Services Task Force (USPSTF) criteria regarding LC risk prediction and efficiency. Methods: We used linked data from 10 Norwegian prospective population-based cohorts, Cohort of Norway. The study included 44,831 ever-smokers, of which 686 (1.5%) patients developed LC; the median follow-up time was 11.6 years (0.01-20.8 years). Results: Within 6 years, 222 (0.5%) individuals developed LC. The NELSON and 2021 USPSTF criteria predicted 37.4% and 59.5% of the LC cases, respectively. By considering the same number of individuals as the NELSON and 2021 USPSTF criteria selected, the HUNT LCM increased the LC prediction rate by 41.0% and 12.1%, respectively. The HUNT LCM significantly increased sensitivity (p < 0.001 and p = 0.028), and reduced the number needed to predict one LC case (29 versus 40, p < 0.001 and 36 versus 40, p = 0.02), respectively. Applying the HUNT LCM 6-year 0.98% risk score as a cutoff (14.0% of ever-smokers) predicted 70.7% of all LC, increasing LC prediction rate with 89.2% and 18.9% versus the NELSON and 2021 USPSTF, respectively (both p < 0.001). Conclusions: The HUNT LCM was significantly more efficient than the NELSON and 2021 USPSTF criteria, improving the prediction of LC diagnosis, and may be used as a validated clinical tool for screening selection.

Pharmacochemical Study of Multitarget Amino Acids' Hybrids: Design, Synthesis, In vitro, and In silico Studies

Introduction: Neuro-inflammation is a complex phenomenon resulting in several disorders. ALOX-5, COX-2, pro-inflammatory enzymes, and amino acid neurotransmitters are tightly correlated to neuro-inflammatory pathologies. Developing drugs that interfere with these targets will offer treatment for various diseases. Objective: Herein, we extend our previous research by synthesizing a series of multitarget hybrids of cinnamic acids with amino acids recognized as neurotransmitters. Methods: The synthesis was based on an in silico study of a library of cinnamic amide hybrids with glycine, γ- aminobutyric, and L - glutamic acids. Drug-likeness and ADMET properties were subjected to in silico analysis. Cinnamic acids were derived from the corresponding aldehydes by Knoevenagel condensation. The synthesis of the amides followed a two-step reaction with 1- hydroxybenzotriazole monohydrate and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in dry dichloromethane and the corresponding amino acid ester hydrochloride salt in the presence of N,N,-diisopropyl-Nethylamine. Results: The structure of the synthesized compounds was confirmed spectrophotometrically. The new compounds, such as lipoxygenase, cyclooxygenase-2, lipid peroxidation inhibitors, and antiinflammatories, were tested in vitro. The compounds exhibited LOX inhibition with IC50 values in the low µM region). Conclusion: Compounds 18a, 23b, and 11c are strong lipid peroxidation inhibitors (99%, 78%, and 92%). Compound 28c inhibits SLOX-1 with IC50 =8.5 µM whereas 11a and 22a highly inhibit COX-2 (IC50 6 and 5 µM Hybrids 14c and 17c inhibit both enzymes. Compound 29c showed the highest anti-inflammatory activity (75%). The in silico ADMET properties of 14c and 11a support their drug-likeness.

Evaluation of Self-Perceived Confidence and Competence in Oral Surgery among Final Year Undergraduate Students in Greece.

OBJECTIVES: Oral surgery is an integral part of dentistry that deals with the diagnosis and management of pathology of the mouth and jaws that requires surgical intervention. The aim of undergraduate studies in oral surgery is, upon graduation, to be confident and competent to treat without assistance surgical cases in the spectrum of general dentistry. This study evaluates the senior Greek dental students' self-confidence and self-perceived competence to undertake cases within the scope of oral surgery. Evaluation of clinical experience gathered during training and self-perceived confidence and competence in generic oral surgery skills is included. MATERIALS AND METHODS: The present study was a questionnaire survey conducted during the academic year 2018-2019. The questionnaire comprised three sections. Section 1 included demographic data and four closed-ended questions concerning numerical data about procedures that they had already performed or observed, section 2 included four questions concerning their self-perceived competence to perform basic surgical techniques, and section 3 included 10 clinical case scenarios. RESULTS: One hundred and twenty-seven students participated in the study. Among the basic surgical skills, students were most confident with suturing, and they were least confident with bone removal. Students from the Aristotle University of Thessaloniki (AUTH) tend to show higher level of confidence compared with students from the National and Kapodistrian University of Athens (NKUA) in most questions. CONCLUSION: Greek graduate dental students report moderate levels of self-confidence in oral surgery. A realistic approach in increasing self-confidence and competence in oral surgery would be the focus on preclinical training in generic elementary surgical skills, in combination with increased observational sessions of oral surgery procedures or outreach training.

The effect of clopidogrel treatment on osseointegration of titanium implants. A histomorphometric study in rabbits.

PURPOSE: Clopidogrel is a P2Y12 purinergic receptor inhibitor and a widely prescribed antiplatelet drug for the prevention of atherosclerotic events. Accumulated evidence suggests that purinergic receptors regulate important functions in bone healing and homeostasis. The purpose of the present study was to evaluate the effect of continuous perioperative clopidogrel treatment on osseointegration of titanium implants. MATERIALS AND METHODS: Thirty two white New Zealand rabbits were randomly assigned in two groups: a clopidogrel group and a control group. Rabbits of the clopidogrel group received daily 3mg/kg of clopidogrel and the control group received vehicle for one week prior to the surgical placement of a titanium implant in their medial femoral condyle; treatment was continued for another six weeks postoperative. At this time, postmortem histologic and histomorphometric evaluation of the implants was performed. RESULTS: Surgical procedures and postoperative period were uneventful and well tolerated by all animals without any surgical wound dehiscence, signs of infection or other complication. No implant failure was observed in any of the groups. Histomorphometric analysis showed that BIC (%) was 48.77% for the clopidogrel group and 34.65% for the control group with statistically significant difference between them (P < 0.001). Moreover, clopidogrel group had significantly greater bone tissue density (40.52 % vs 28.74 %, p<0.001) and mean trabecular thickness (284.7 µm vs 180.7 µm, p<0.001) in proximity to the implant surface, while mean trabecular number had no difference between groups (1.56 vs 1.60, p=0.961). CONCLUSIONS: The present study showed that continuous clopidogrel treatment does not negatively affect osseointegration, but rather promotes it in terms of BIC and bone density around the titanium implants. Further studies on the effect of the P2Y12 receptor and its antagonists on peri-implant bone homeostasis may provide useful information or applications for long-term success of dental implant therapy.

"Shot on Target": A Case of an Unusual Peripheral Ossifying Fibroma of the Edentulous Upper Jaw Irritated by the Only Teeth of the Lower Jaw.

A peripheral ossifying fibroma (POF) is a benign, localized lesion that originates from the periosteum or periodontal ligament after traumatic or calculus irritation. The lesions typically manifest in females throughout their second and third decades of life. The diagnosis of a POF is challenging from both clinical and histological standpoints, as it exhibits overlapping features with numerous other clinical entities. This case describes an unusual occurrence of POFs in the anterior maxilla of a 66-year-old female patient who is edentulous at this jaw, but the last two teeth of the lower jaw affect it. The radiographic evaluation revealed no discernible alterations within the bone structure. The diagnosis of POFs was determined through histological investigation. The microscopic examination revealed scattered immature osteoid dystrophic calcified depositions in deep positions, whereas the overlying stratified squamous epithelium manifested frictional keratosis (hyperplasia). The stromal fibroblasts of the collagenous stroma displayed ovoid, normochromatic nuclei, without atypia. Interestingly, the particular importance of this POF case indicates the possibility of an atypical formation in terms of age and location suggesting the role of local chronic irritation as the most critical parameter. Regardless of the initial causative factor, which may be the remnants of the periodontal ligament, the periosteum, or the gingival fibroblasts, ultimately mechanical trauma constitutes the crucial prerequisite so that reactive hyperplasias may be induced.

Rare Case of Peripheral Myxofibroma of Anterior Maxillary Gingiva: A Diagnostic Challenge.

The myxofibroma (MF) constitutes an uncommon, non-malignant, odontogenic neoplasm with potential mesenchymal derivation. The occurrence rate of this particular tumor is estimated to be around 0.05 new cases per million individuals annually. MFs exhibit a higher incidence rate within the age range of 10 to 30 years. The prevalence of these tumors is higher among the female population, with a predominant localization in the mandible, specifically in the posterior region. A female patient, 66 years old, was referred to the Department of Oral Surgery, Surgical Implantology and Radiology, Thessaloniki, Greece, complaining of a tumorous lesion in the anterior area of the maxilla and mild pain. Clinically, a solid in palpation lobulated tumor, covered by normal coloured mucosa was observed at the left upper incisor. After the excisional biopsy, the microscopic appearance of abundant fibromyxoid stroma, in particular, myxoid stroma intermingled with collagenous tissue, covered by stratified squamous epithelium, suggested the diagnosis of peripheral myxofibroma. During a 2-year follow-up, no recurrence was referred. This case illustrates the necessity of proper differential diagnosis of every tumorous lesion of the gingiva and of using the histopathological examination.

Mental and Lingual Nerve Paresthesia Following Infiltration Anesthesia for Dental Implant Placement in a Patient With Guillain-Barré Syndrome.

Guillain-Barré syndrome (GBS) is a rare rapid onset autoimmune peripheral polyneuropathy, most commonly characterized by inflammatory demyelination of peripheral nerves. Patients with GBS are considered higher risk for anesthetic-induced neurotoxicity caused by demyelination. In the present report, a case is described of a 56-year-old man with GBS who experienced mental and lingual nerve paresthesia following infiltration anesthesia for dental implant placement in the posterior mandible. The pareshesia lasted 5 months postoperatively and subsided spontaneously without any intervention. The patient was successfully restored with fixed partial dental prosthesis without any other complication. This is considered the first report of such complication in patient with GBS after local anesthesia in the oral and maxillofacial region. Possible pathogenic mechanism of the complication and clinical implications are discussed.

Anesthetic efficacy of buffered 4% articaine for mandibular first molar infiltration: a crossover clinical trial.

Background: The limited studies on the effect of buffering on the clinical efficacy of articaine have reported controversial results. The purpose of this study was to clinically compare the pain of injection, anesthetic success, onset, and duration of pulpal anesthesia of buffered 4% articaine with epinephrine 1:100000 versus a non-buffered 4% articaine with epinephrine 1:100000 formulation for buccal infiltration of the mandibular first molar. Methods: Sixty-three volunteers were enrolled in the study. All volunteers received two injections consisting of a single mandibular first molar buccal infiltration with 1.8 ml of 4% articaine with epinephrine 1:100000 and 1.8 ml of 4% articaine with epinephrine 1:100000 buffered with 8.4% sodium bicarbonate. The infiltrations were applied in two separate appointments spaced at least one week apart. After injection of the anesthetic solution at the examined site, the first molar was pulp-tested every 2 min for the next 60 min. Results: Successful pulpal anesthesia was recorded in 69.8% of cases using non-buffered articaine solution and 76.2% of cases using buffered articaine solution, with no significant difference between the formulations (P = 0.219). The mean time of anesthesia onset for the volunteers with successful anesthetic outcome in both formulations (n = 43) was 6.6 ± 1.6 min for the non-buffered articaine solution and 4.5 ± 1.6 min for the buffered solution, which differed significantly (P = 0.001). In the same volunteers, the mean duration of pulpal anesthesia was 28.4 ± 7.1 min for non-buffered articaine solution and 30.2 ± 8.5 min for buffered articaine solution, with no significant difference between the formulations (P = 0.231). Considering the pain of injection, regardless of the anesthetic success, the mean values of VAS were 11.3 ± 8.2 mm for the non-buffered articaine solution and 7.8 ±6.5 mm for the buffered articaine solution, which differed significantly (P = 0.001 < 0.05). Conclusion: According to the present study, 4% articaine with epinephrine can benefit from buffering and provide better anesthetic behavior, with improved onset and less pain during injection.

Optimizing the Distillation of Greek Oregano-Do Process Parameters Affect Bioactive Aroma Constituents and In Vitro Antioxidant Activity?

The aim of the present work was to optimize the conditions of the distillation process at a pilot scale to maximize the yield of specific bioactive compounds of the essential oil of oregano cultivated in Greece, and subsequently to study the in vitro antioxidant activity of these oils. Steam distillation was conducted at an industrial distillery and a Face-Centered Composite (FCC) experimental design was applied by utilizing three distillation factors: time, steam pressure and temperature. Essential oil composition was determined by static headspace gas chromatography-mass spectrometry (HS-GC/MS). To obtain a comprehensive profile of the essential oils, instrumental parameters were optimized, including sample preparation, incubation conditions, sampling process, injection parameters, column thermal gradient and MS conditions. With the applied GC-MS method, more than 20 volatile compounds were identified in the headspace of the oregano essential oils and their relative percentages were recorded. Carvacrol was the most prominent constituent under all distillation conditions applied. Data processing revealed time as the main factor which most affected the yield. The Desired Space (DSc) was determined by conducting a three-dimensional response surface analysis of the independent and dependent variables, choosing yields of thymol and carvacrol as optimization criteria. The in vitro antioxidant activity of the essential oils of all samples was measured in terms of the interaction with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) after 20 and 60 min. The most prominent essential oils at different distillation conditions were also tested as inhibitors of lipid peroxidation. Higher % values of carvacrol and thymol were correlated to higher antioxidant activity. Evaluating the impact of the distillation conditions on the in vitro results, it seems that lower pressure, less time and higher temperature are crucial for enhanced antioxidant activities.

A Differential Clinical Diagnostic Challenge of a Recurrent, Oral Fibrosarcoma Resembling a Periapical Lesion of Endodontic Origin.

A fibrosarcoma is a neoplastic growth originating from malignant, fibroblast-like mesenchymal cells. This malignant tumor shows an increased tendency for expansion and recurrence and a propensity to metastasize, especially to the lungs. Despite their rarity, fibrosarcomas have the potential to manifest in any anatomical location. An oncologist referred their patient due to reported mandibular discomfort, ache, and swelling. The biopsy revealed a fibrosarcoma resembling a periapical lesion of endodontic origin. The timely intervention and the collaboration among different but complementary medical and dental specialties ensure that the patient may enjoy a prolonged life expectancy as symptom-free as possible.

A Case Report of Ibandronic Acid Induced Non-Exposed BRONJ Involving the Maxillary Sinus.

Background: The aim of this case report is to present an interesting case of bisphosphonate-related osteonecrosis of the jaw, involving the maxilla and the maxillary sinus, as a result of per os administration of ibandronic acid. Methods: A female patient, 62 years old, was referred to the Department of Dentoalveolar Surgery, Surgical Implantology and Radiology, School of Dentistry, Aristotle University of Thessaloniki, Greece, complaining about pain in the first quadrant. Her medical history revealed per os bisphosphonate administration for the past four years. Subsequently, the cone-beam computed tomography examination revealed a small sequestrum of bone, surrounded by radiolucency, in proximity with the sinus floor. The clinical examination didn't reveal any pathological clinical signs. Results: Based on the radiological examination, a surgical approach was implemented to remove the necrotic bone, irrigate the alveolar process and the sinus with saline, and finally achieve primary closure, after which, the patient healed uneventfully. The osteonecrosis was attributed to the bisphosphonate administration. Conclusions: Bisphosphonate-related osteonecrosis of the jaw without obvious or with minor implication of gingival tissues is a diagnostic challenge indicating an early stage of this adverse reaction. Imaging is critical for the early detection of those cases. After careful choice of the case the proper surgical intervention could be effective to eliminate a future advancement of bone destruction. The prevention of osteonecrosis of the jaw can be achieved through the provision of adequate education to dental medicine practitioners, medical doctors, and patients.

Accuracy of dental implant placement with 3D-printed surgical templates by using Implant Studio and MGUIDE. An observational study.

AIM: The purpose of the present study was to report early surgical template-related and postoperative complications of computer-guided implant placement and to evaluate its accuracy. MATERIALS AND METHODS: Data were collected retrospectively from records of patients who had undergone computer-guided implant surgery between 2016 and 2018. Incidence of early surgical template-related and postoperative complications was recorded. Accuracy of implant placement was evaluated by comparing the data from postoperative CBCT records with that from the preoperative virtual implant planning by using appropriate image registration software. Depth, coronal, apical, and angular deviations were measured. RESULTS: A final number of 27 partially edentulous patients who received 52 implants with 31 static surgical templates were included in the study. All implants had been inserted in a fully guided manner using a flapless technique and following a one-stage approach. All implants were reported to have been successfully osseointegrated. Except for one template fracture, no other complication was recorded. The mean depth deviation was 0.57 ± 0.4 mm (95% CI 0.48 to 0.71 mm), the mean coronal deviation was 0.89 ± 0.7 mm (95% CI 0.73 to 1.07 mm), the mean apical deviation was 1.4 ± 1 mm (95% CI 1.16 to 1.71 mm), and the mean angular deviation was 2.74 ± 1.8 degrees (95% CI 2.29 to 3.26 degrees). CONCLUSION: The use of static surgical templates for fully guided implant placement demonstrated acceptable clinical performance. However, there are some factors affecting accuracy that should be considered during implant planning and surgery for further improvement of the technique. (Int J Comput Dent 2022;25(3):249-256; doi: 10.3290/j.ijcd.b2599735).

Hybrids of Coumarin Derivatives as Potent and Multifunctional Bioactive Agents: A Review.

BACKGROUND: Coumarins exhibit a plethora of biological activities, e.g. antiinflammatory and anti-tumor. Molecular hybridization technique has been implemented in the design of novel coumarin hybrids with several bioactive groups in order to obtain molecules with better pharmacological activity and improved pharmacokinetic profile. OBJECTIVE: Therefore, we tried to gather as many as possible biologically active coumarin hybrids referred in the literature till now, to delineate the structural characteristics in relation to the activities and to have a survey that might help the medicinal chemists to design new coumarin hybrids with drug-likeness and varied bioactivities. RESULTS: The biological activities of the hybrids in most of the cases were found to be different from the biological activities presented by the parent coumarins. The results showed that the hybrid molecules are more potent compared to the standard drugs used in the evaluation experiments. CONCLUSION: Conjugation of coumarin with varied pharmacophore groups/druglike molecules responsible for different biological activities led to many novel hybrid molecules, with a multitarget behavior and improved pharmacokinetic properties.

Cinnamate Hybrids: A Unique Family of Compounds with Multiple Biological Activities.

Cinnamic acid derivatives are widely distributed in nature presenting a wide range of biological activities: antiseptic, stimulant, carminative and insecticidal activities. Hydroxy- cinnamic acids, especially caffeic, ferulic and chlorogenic, present various biological activities and they are synthesized in nature through the phenylpropanoid pathway. Additionally, the cinnamoyl moiety is present in various drugs such as a) Ozagrel, an imidazole π - substituted cinnamic acid acting as a thromboxane A2 synthase inhibitor, used therapeutically for treating acute ischemic stroke, b) Cinnarizine, Cinanserin and Tranilast, a series of antiallergic agents etc. During the last decade, scientists have focused on multifunctional molecules instead of a single molecule hitting one target. Multi-target drugs can be beneficial for the treatment of complex and multifunctional diseases. A variety of multi-target drugs contain the cinnamic acid moiety due to its biological importance and combination of biological activities e.g. antioxidant, antiiflammatory, anticancer, antituberculosis, antifungal, antimalarial, antiatherogenic, antimicrobial activities. Recently for the treatment of complex diseases hybrid drugs combining two pharmaceutical moieties in one molecule have been developed. These molecules are more medically effective than their individual components. In this review, a survey of cinnamate hybrids, that is molecules that combine the cinnamic acid moiety with at least a second pharmacophore with or without a linker, acting as "multi-target" agents, is given. The hybrids are listed in terms of their biological activity and applications as anti-Alzheimer, anticancer agents as well as for cardiovascular diseases, as antivirals, antimalarials etc.