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In Vivo Toxicity and In Silico Molecular Docking of NXH8, a Post-Synaptic Three-Finger Toxin from Micrurus corallinus, in Comparison to α-Bungarotoxin.
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Introduction: Coral snakes of the genus Micrurus, primary representatives of the family Elapidae in the Americas, contain potent neurotoxins, making envenomation highly dangerous. In Brazil, M. corallinus and M. frontalis cause most bites. Recently, NXH8, a three-finger toxin (3FTx) with antagonistic activity on nicotinic acetylcholine receptors (nAChR), was characterized. Methods: Anti-NXH8 antibodies were produced in Balb/c mice. In vivo toxicity was assessed in mice receiving 3 LD50 of M. corallinus venom (control) or synthetic NXH8. The neutralizing capacity of anti-NXH8 antibodies was tested in mice injected with venom pre-incubated with saline (G1), antivenom (G2), anti-NXH8 antibodies (G3), and post-treated with Varespladib (VPL) intramuscularly after intraperitoneal administration of venom pre-incubated with saline (G4) or pre-incubated with anti-NXH8 antibodies (G5). Survival was monitored for 48 hours. Results: Mice injected with venom pre-incubated with saline (G1) died in 6.00 ± 1.22 hours, while those injected with venom pre-incubated with antivenom (G2) survived for more than 48 hours. Anti-NXH8 antibodies (G3) resulted in a survival time of 7.2 ± 0.84 hours, with no significant difference from G1 (p = 0.108). VPL administration post-venom (G4) increased survival to 10.2 ± 0.45 hours (p < 0.05). VPL post-venom pre-incubated with anti-NXH8 (G5) increased survival to 11.0 ± 1.22 h, not significantly different from G4 (p = 0.207). Docking simulations indicated that NXH8 binds to nAChR but lacks crucial residues for effective interaction, explaining its low toxicity. Conclusion: NXH8's low toxicity in vivo is likely due to structural differences from α-bungarotoxin, suggesting that other venom toxins, including presynaptic β-neurotoxins such as Phospholipase A2 (PLA2), may contribute to lethality. This study was conducted under Animal Ethics Committee Protocol 4463100419 with financial support from H.R-R. (FAPESP: 2017/18398-1) and S.H. (CNPq: 406816/2022-0).

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Needle-guided scleral fixation IOL: easy technique for beginner surgeons

To propose a very safe and efficient method for scleral fixation IOL applicable in all cases of aphakia and dislocated or subluxated lens and malpositioned IOL. This method is suitable for both experienced and inexperienced surgeons eliminating the need for a vitreoretinal surgeon, trocars or the risk of haptics rupture.

Methods: Fifteen patients, each with dislocated lens or subluxated lens, aphakia pr malpositioned IOL in one eye, underwent transscleral needle-guided fixation of a PMMA single piece IOL. A long needle (e.g. CTC-6L, STC-6 or CIF-4) was inserted into a 24-gauge cannula. This assembly was passed from superotemporal sclerotomy (3 mm from the limbus) to superonasal sclerotomy (3 mm from the limbus). The needle was then loaded with double armed polypropylene 9-0 suture which passed through and emerged from the superotemporal incision, thus creating a single suture strand from nasal to temporal sides, each end carrying a needle -one straight and the other curved. The suture’s extremities were knotted to the haptics of the single piece PMMA IOL’ loops and inserted into the AC through a 6 mm corneal incision, applying torsional forces in opposite directions, making the IOL less easily tiltable. Sutures were placed both on the sclera and cornea after the implant. Results: Visual acuity was of 0.1 Logmar in every patient on day one after the procedure. No IOL tilting was noted. Mild conjunctival hyperemia was present in 70% of the eyes. Conclusion: the needle-guided scleral fixation IOL is a highly safe and effective technique, even for a two-time surgery, in all cases of aphakia, dislocated/subluxated lens and malpositioned IOL. The pros of this technique are the safety of non tilting of the IOL, the absence of risk for subsequent vitrectomy due to IOL dislocation into the vitreous chamber and, its ease of reproducibility even for inexperienced surgeons.

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Unveiling the Link: How Personality Traits Influence Central Serous Chorioretinopathy Through OCT and Psychological Assessment

Central Serous Chorioretinopathy (CSCR) is a retinal condition characterized by the accumulation of subretinal fluid, leading to visual disturbances. Although the exact pathophysiology remains unclear, its etiology can be considered multifactorial, with stress and personality traits being significant contributors.T his study involved 44 participants, half having been diagnosed with CSCR and the other half serving as controls. Comprehensive data, including medical history, symptomatology, and corticosteroid use, were collected. Psychological assessments were conducted using the Personality Inventory for DSM-5–Brief Form (PID-5-BF) and TEMPS-A-brief. Optical coherence tomography (OCT) was used to evaluate choroidal thickness, photoreceptor alteration, pigment epithelium detachment, and macular edema. The results indicated a higher prevalence of CSCR in men (male-to-female ratio of 1:10) with an average age of 50.55 years. A correlation between increased choroidal thickness and age was noted, with older patients showing higher values and complications like secondary choroidal neovascularization. Corticosteroid use did not correlate with increased choroidal thickness. Psychological assessments revealed no significant correlation between CSCR and specific personality domains; however, a trend towards higher negative affectivity was observed in CSCR patients. In conclusion, the study's epidemiological findings align with those in the existing literature, emphasizing a higher prevalence of CSCR in males and increased choroidal thickness with age. Although no direct correlation between personality traits and CSCR was statistically validated, a trend towards negative affectivity suggests a potential link. The interplay between psychological factors and CSCR warrants further investigation, and understanding the role of mental states in CSCR's onset and progression could inform integrated management strategies. The results underscore the need for larger sample sizes to confirm these preliminary findings and to explore the mechanisms underlying CSCR's association with psychological stress and choroidal dysfunction.






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In vitro antibacterial activity of native and encapsulated mangiferin against ESKAPE bacteria

Nowadays, one of the major healthcare problems is the strong increase in the prevalence of resistant bacterial infections. The ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp) is defined among clinically relevant bacteria, as these pathogens cause the majority of nosocomial infections and have increasing multidrug resistance and virulence. One of the options for alternative treatment of resistant bacterial infections is the use of natural bioactive agents derived from plants with antibacterial properties. The effectiveness of these natural compounds consists in their chemical composition, which allows them to affect multiple sites of bacterial cells and disrupt their essential biological processes. In addition, due to their diverse mechanisms of action, plant secondary metabolites are less likely to induce resistance in pathogens.

Mangiferin is a unique xanthone derivative, one of the main sources of which is Mangifera indica. Besides antibacterial activity, this secondary metabolite has numerous pharmacological effects, including antioxidant, antiviral, antidiabetic, anticancer, immunomodulatory, hepatoprotective, analgesic and anti-aging properties.

In vitro studies have shown that mangiferin has a synergistic effect when used with existing antibiotics and/or exhibits an independent inhibitory effect against almost all ESKAPE group bacteria. In addition, there is an opportunity to improve the antibacterial properties of secondary metabolites using various methods, including loading them into polymer matrix-based delivery systems.

In this work, we collected information on the antibacterial properties of mangiferin against the ESKAPE group of pathogens. This review will contribute to future antimicrobial studies of this bioactive compound and to the search for methods of its encapsulation to improve these properties.

This research was funded by the Russian Science Foundation, project number 24-23-00269. Link to information about the project: https://rscf.ru/en/project/24-23-00269/

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Advancing Dental Diagnostics with AI: UNet for Precision in Treatment and Anatomy Mapping

Medical imaging methods are crucial in dental patient care for diagnosing pathologies related to teeth and surrounding structures. Radiological techniques, such as cone-beam computed tomography (CBCT), are vital for orthodontic diagnosis, treatment planning, and monitoring. With the increasing number of radiological examinations, there is a growing need for comprehensive diagnostic tools. To address this, Artificial Intelligence (AI)-based systems have emerged. Machine Learning (ML) has significantly impacted medical specialties, including orthodontics, offering promising results. ML enables early screening, accurate diagnosis, appropriate treatment, and prediction of treatment-associated toxicity for maxillofacial cysts and tumors. Additionally, ML models are valuable for planning, evaluating, and improving dental implants. The purpose of this work was to develop an algorithm for dentistry aimed at recognizing pathologies observable in second-level instrumental investigations, to present them in a simplified way both to expert dentists and those who intend to approach image reading. Six patients (3M, 3F, ages 29-61) with various dental treatments were selected. UNet was used for segmentation, performing pixel-wise classification to localize and distinguish the edges of structures in the images. The model's architecture allows the input and output to share the same dimensions, facilitating accurate delineation of dental structures. The training utilized a dataset of annotated images to enhance the model's capacity to identify and differentiate various dental treatments and conditions. Once training was complete, the neural network was tested on a separate dataset known as the test set, which consisted of data not used during the former phase. This testing phase aimed to evaluate the neural network’s performance in practical scenarios and provide an objective estimate of its segmentation capabilities. UNet effectively demonstrated its ability to precisely identify and highlight structures of interest, including those that are smaller in size, thereby reducing the manual workload of dental operators.

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Digital design can be simplified in routine clinical practice: A hybrid digital–analogue technique for maxillary overdenture fabrication.

This article describes a hybrid digital–analogue workflow for the fabrication of a maxillary overdenture prosthesis, as opposed to an implant-based overdenture. This procedure provides a predictable and accurate technique in five visits by integrating digital and analogue workflows, guided prosthetic surgery, 3D printers and classical total denture techniques.

The introduction of digital technology into the dental world has enabled 3D programming in surgery, prosthetics and orthodontics.

The combined use of intra-oral scanners (IOS), facial scanners and cone beam computer tomography (CBCT) enables the virtual reconstruction of the patient and the design of surgical guides for implant-supported prostheses by means of various types of computer-aided design (CAM) software. The use of optical impressions makes it possible to decrease patient discomfort, as well as speed up and improve communication with the dental laboratory. However, optical impressions present challenges in reporting the resilience characteristics of the mucosa in edentulous patients. A possible solution to improve the performance of the digital workflow is the integration of the analogue technique. The implant-retained overdenture of the upper jaw allows for a significant improvement in chewing ability, speech, sociability and the psychological well-being of patients compared to mucosa-only restorations, with a lower cost of the overdenture.

The overdenture prosthesis is a viable therapeutic choice for all patients in need of total rehabilitation. The use of a hybrid digital–analogue protocol allows for the advantages of both protocols to be combined with speed, precision, comfort, reliability, reproducibility and efficiency.

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Evaluating the Failure Rates of Dental Crowns on Endodontically Treated Teeth: A Comprehensive Review of Contributing Factors and Clinical Outcomes

A comprehensive review of the literature was conducted, focusing on clinical studies, retrospective analyses, and systematic reviews that reported the failure rates of crowns placed on endodontically treated teeth. Factors such as the type of crown material, quality of root canal treatment, crown-to-root ratio, occlusal forces, and the presence of residual tooth structure were examined. Data were synthesized to identify common patterns and potential predictors of failure. This review revealed that the failure rates of crowns on endodontically treated teeth vary widely, with mechanical failures such as crown dislodgement, fractures, and secondary caries being the most prevalent. Factors such as inadequate root canal obturation, poor crown fit, insufficient ferrule effect, and high occlusal stress were strongly associated with increased failure rates. Additionally, the use of certain crown materials, such as metal–ceramic and all-ceramic crowns, showed different performance outcomes based on the clinical scenario. The success of crown restorations on endodontically treated teeth is highly dependent on multiple factors, including the quality of endodontic treatment, crown design, material selection, and proper case management. To reduce failure rates, clinicians should focus on ensuring optimal root canal therapy, using appropriate crown materials, and adhering to principles such as achieving a sufficient ferrule. Continued research and advances in dental materials and techniques are essential to further enhance the outcomes of these rehabilitations.

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Addressing Scientific Misconduct in Dental Publications: From Predatory Journal to Artificial Intelligence Misuse

Scientific misconduct and the misuse of artificial intelligence (AI) pose significant threats to the integrity of academic research, particularly in the field of dental publications. This paper provides a comprehensive review of various forms of malpractice, including citation doping, the proliferation of predatory journals, inappropriate citation requests, and the unethical application of AI in research and publication processes. These malpractices undermine the credibility and reliability of scientific outputs, compromising the advancement of knowledge and evidence-based practices. This review highlights the impact of citation doping, a practice where authors manipulate citation counts to enhance their academic profiles unethically. Additionally, the rise of predatory journals, which prioritize profit over scholarly integrity, is discussed. Inappropriate citation requests, where authors are pressured to include unnecessary citations to inflate the impact factors of certain journals, are examined for their detrimental effects on research quality. The misuse of AI, including the generation of fraudulent data and plagiarism, is critically analyzed. By drawing on international guidelines and best practices, this paper proposes a robust framework to promote ethical research and publication practices. The measures recommended aim to enhance the quality and credibility of research in the dental field, ensuring that scientific contributions are both trustworthy and valuable.

Scientific integrity is the cornerstone of academic research, yet recent trends have highlighted significant issues of misconduct within the field of dental publications. These malpractices include citation doping, the use of non-peer-reviewed journals, predatory publishing, and the emerging misuse of artificial intelligence (AI) in research processes. This paper aims to discuss these issues, summarize expert interventions, and propose a set of guidelines to combat scientific misconduct and AI misuse.

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Affective Temperaments and Depressive Rumination in an Italian–Spanish sample with bruxism
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Introduction

Bruxism, a condition characterized by teeth grinding or clenching, is a complex issue influenced by various factors. From a mental health perspective, bruxism has been linked to psychopatological variables, i.e., anxiety, depression and ruminative thinking. The aim of this study is to investigate the psychological traits associated with affective components in an Italian–Spanish sample with bruxism.

Method

In total, 581 subjects were examinated and data were collected through online survey including the Ruminative Response Scale (RRS) and the Brief Italian Version of the TEMPS-A (Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire). Differences between the groups were assessed using Student’s t-test for independent samples. In addition, a linear regression analysis was performed, in which the Ruminative Response Scale variable was considered the dependent variable, and all the TEMPS-A factors were included in the equation, to assess which temperamental dimensions could act as specific predictors of depressive rumination in patients with bruxism.

Results

The analyses revealed statistically significant gender differences concerning Depressive, Cyclothymic, Hyperthymic, and Anxious temperaments, as well as components of Depressive Rumination. Furthermore, linear regression analysis showed that Depressive, Cyclothymic, and Anxious temperaments are predictive of the Depressive Rumination variable.

Conclusions

These preliminary results suggest the relevance of affective temperaments and Depressive Rumination in the clinical population of patients with bruxism.

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Study of the antimicrobial activity of new 1,3,5-triazine derivatives
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Introduction: 1,3,5-triazine derivatives are an important class of heterocyclic compounds that have a wide range of biological activities, including exhibiting strong antimicrobial activity. Thus, the preparation of new compounds based on a triazine core, as well as the study of their antimicrobial activity, is an urgent task. Methods: The target compounds were obtained by the recyclization of 2-aryl-4-hydroxy-5-methyl-6H-1,3-oxazin-6-ones (1-3) with ethanimidamide and benzenecarboximidamide, which are 1,3-binucleophilic reagents. The reaction was carried out in the presence of an amount of sodium propoxide equimolar to the nucleophile in boiling n-propanol for 2-5 hours. The structure of the obtained compounds (4-9) was proven using modern physico-chemical methods of analysis: 1H and 13C NMR spectroscopy, IR spectroscopy, and mass spectrometry. The antimicrobial activity potential of the synthesized compounds was determined by computer analysis using the AntiBac Pred online service. Experimentally, the antimicrobial activity of the compounds was studied by the method of serial dilutions against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) test cultures of microorganisms. Results and conclusions: The target compounds were obtained in 58-88% yield. As a result of in silico computer screening using the AntiBac Pred online service, data on the potential antimicrobial effect of the target compounds were obtained. Using experimental microbiological studies, it was shown that the studied compounds have moderate antimicrobial activity against the test cultures studied. Analyzing the structure–activity relationship, it was found that compounds that have a methyl group in position 2 of the triazine ring have the strongest inhibitory effect. The inhibitory activity against Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa) is strongest for triazines that have a methyl group in position 2 and electron-donating substituents in the benzene ring.

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