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Background/Objectives: The presence of enamel on the tooth surface is crucial for the long-term success of minimally invasive adhesive restorations such as dental veneers. Our study aims to evaluate the enamel thickness in the incisal, middle, and cervical portions of the labial surface of the upper central incisors using cone beam computed tomography (CBCT). This imaging method provides detailed and accurate three-dimensional images with a low radiation dose, allowing an accurate assessment of enamel thickness. The analysis aims to identify variations in enamel thickness depending on the age and different levels of the labial tooth surface. Methods: 800 CBCT scans performed for diagnostic or therapeutic purposes on patients aged 18–60 years were analyzed. The data were gathered from the imaging archives of private practitioners from Targu Mures and the “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Targu Mures. Enamel thickness measurements were conducted using the OnDemand3D Communicator CBCT evaluation program, with subsequent statistical analysis performed using GraphPad Instat Prism software. Results: Results showed significant variation in enamel thickness between the incisal, middle, and cervical segments of the labial surface of the upper central incisors. A decrease in enamel thickness with age has been observed. In patients aged 18–40, mean values of enamel thickness 1 mm and 3 mm above the cementoenamel junction (CEJ) were 0.48 ± 0.092, respectively, 0.819 ± 0.158. In patients over 40, the mean values were 0.454 ± 0.116 and 0.751 ± 0.067 at 1 mm, respectively, 3 mm above the CEJ. Statistically significant differences were found between the two age groups at 1 mm and 3 mm above the CEJ, with p < 0.0001 and p = 0.0214. Conclusions: A statistically significant decrease can be observed in enamel thickness in almost the entire labial surface of the upper central incisors with aging. The varied thickness of the enamel at different tooth levels requires individualized planning for each patient to maximize the long-term aesthetic and functional results.

Background: Intraoral scanning technology has opened new perspectives in dental practice, and combined with CAD/CAM technology, contributes significantly to fabricating high-quality prosthetic restorations. Our in vitro study aims to assess the accuracy of digital models obtained from one laboratory and two less commonly used intraoral scanners by conducting 3D measurements on the digital models obtained. Methods: An articulated simulator cast was used. Forty-eight scans were performed before and after tooth preparation with each scanner. The Zeiss Inspect software (Version: 2023.3.0.969) was used for measurements in sagittal and transversal planes. The obtained values were compared to reference values resulting from manual measurements. Results: Digital impressions provided discrepancies compared to the reference model. The lowest differences at the A2-L2 (the diagonal dimension of the models from the distal fossa of the second right maxillary molar and the maximum oral convexity of the artificial gingiva at the first left premolar) and the A1-B1 (transversal dimension of the model in the posterior area, from the right second molar’s occlusal central fossa to the left second molar central fossa) distances were obtained for the upper models, and at the a1-b1 distance for all the lower models, except the non-prepared models scanned with the intraoral scanners (the discrepancies were not statistically significant). The discrepancies increased with the distance from the starting point of the scan. Conclusion: The number and position of prepared teeth can influence the accuracy of the scans. Distortions can appear in the case of multiple preparations. The scanning protocol and calibration must be optimized for the highest accuracy. Furthermore, in vivo studies are necessary to evaluate the clinical applicability of these findings.

Rheumatoid arthritis (RA) is recognized as an autoimmune joint disease driven by T cell responses to self (or modified self or microbial mimic) antigens that trigger and aggravate the inflammatory condition. Newer treatments of RA employ monoclonal antibodies or recombinant receptors against cytokines or immune cell receptors as well as small-molecule Janus kinase (JAK) inhibitors to systemically ablate the cytokine or cellular responses that fuel inflammation. Unlike these treatments, a therapeutic vaccine, such as CEL-4000, helps balance adaptive immune homeostasis by promoting antigen-specific regulatory rather than inflammatory responses, and hence modulates the immunopathological course of RA. In this review, we discuss the current and proposed therapeutic products for RA, with an emphasis on antigen-specific therapeutic vaccine approaches to the treatment of the disease. As an example, we describe published results of the beneficial effects of CEL-4000 vaccine on animal models of RA. We also make a recommendation for the design of appropriate clinical studies for these newest therapeutic approaches, using the CEL-4000 vaccine as an example. Unlike vaccines that create or boost a new immune response, the clinical success of an immunomodulatory therapeutic vaccine for RA lies in its ability to redirect autoreactive pro-inflammatory memory T cells towards rebalancing the “runaway” immune/inflammatory responses that characterize the disease. Human trials of such a therapy will require alternative approaches in clinical trial design and implementation for determining safety, toxicity, and efficacy. These approaches include adaptive design (such as the Bayesian optimal design (BOIN), currently employed in oncological clinical studies), and the use of disease-related biomarkers as indicators of treatment success.

Abstract Background The parasitic nematode Spirocerca lupi (Spirurida: Thelaziidae), the canine esophageal worm, is the causative agent of spirocercosis, a disease causing morbidity and mortality in dogs. Spirocerca lupi has a complex life cycle, involving an obligatory coleopteran intermediate host (vector), an optional paratenic host, and a definitive canid host. The diagnosis of spirocercosis is challenging, especially in the early disease stages, when adult worms and clinical signs are absent. Thus, alternative approaches are needed to promote early diagnosis. The interaction between nematodes and their bacterial symbionts has recently become a focus of novel treatment regimens for other helminthic diseases. Results Using 16S rDNA-based molecular methods, here we found a novel bacterial symbiont in S. lupi that is closely related to Comamonas species (Brukholderiales: Comamonadaceae) of the beta-proteobacteria. Its DNA was detected in eggs, larvae and adult stages of S. lupi. Using fluorescent in situ hybridization technique, we localized Comamonas sp. to the gut epithelial cells of the nematode larvae. Specific PCR enabled the detection of this symbiont's DNA in blood obtained from dogs diagnosed with spirocercosis. Conclusions The discovery of a new Comamonas sp. in S. lupi increase the complexity of the interactions among the organisms involved in this system, and may open innovative approaches for diagnosis and control of spirocercosis in dogs.

Perceptions of the complete eradication of vaccine-preventable diseases such as measles, mumps, and rubella (MMR) may foster complacency and compromise vaccination efforts. Decreased measles vaccination rates during the COVID-19 pandemic have heightened the risk of outbreaks, even in adequately vaccinated populations. To address this, we have aligned with ECDC recommendations, leveraging previous cross-border sero-epidemiological assessments between Pécs, Hungary, and Osijek, Croatia, to identify latent risk groups and uncover potential parallels between our nations. Testing 2680 Hungarian and 1764 Croatian serum samples for anti-MMR IgG via ELISAs revealed anti-measles seropositivity ratios below expectations in Croatian cohorts aged ~20–30 (75.7%), ~30–40 (77.5%) and ~40–50 years (73.3%). Similarly, Hungarian samples also showed suboptimal seropositivity ratios in the ~30–40 (80.9%) and ~40–50 (87.3%) age groups. Considering mumps- and rubella-associated seropositivity trends, in both examined populations, individuals aged ~30–50 years exhibited the highest vulnerability. Additionally, we noted congruent seropositivity trends across both countries, despite distinct immunization and epidemiological contexts. Therefore, we propose expanding research to encompass the intricate dynamics of vaccination, including waning long-term immunity. This understanding could facilitate targeted interventions and bolster public awareness. Our findings underscore persistent challenges in attaining robust immunity against measles despite vaccination endeavors.

Willow (Salix spp.) trees, found worldwide, contain secondary metabolites that are valuable as dietary supplements for animal feed and as antiparasitic compounds. We quantified secondary metabolites (phenolics, flavonoids, and salicylic acid) in ethanolic extracts from leaves and branches of three Salix acmophylla Boiss. genotypes and investigated their potential to inhibit Eimeria sp. sporulation, a major concern in ruminants. The total phenolic content of willow leaves and branches was similar in two of three different genotypes. The total flavonoid content of the branches was significantly higher than that of leaves of the same genotype; however, the salicylic acid content was significantly higher in leaves than in branches. Importantly, all extracts exhibited significant inhibition of Eimeria sporulation, where over 70% inhibition was obtained at concentrations as low as 750 mgL−1. The sporulation inhibition by branch or leaf extracts exceeded 80% for leaves and 90% for branches at concentrations above 1250 mgL−1. The study highlights the potential of using Salix extracts as bioactive compounds for biological control of coccidiosis in ruminants. We conclude that all parts and all investigated genotypes of S. acmophylla can provide secondary metabolites that act as a coccidiostat to treat Eimeria in goats.

Subject and purpose of work: The aim of the study is to describe the development of the social economy sector, the emergence of social enterprises and the rationale for their establishment.

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background/Objectives: The presence of enamel on the tooth surface is crucial for the long-term success of minimally invasive adhesive restorations such as dental veneers. Our study aims to evaluate the enamel thickness in the incisal, middle, and cervical portions of the labial surface of the upper central incisors using cone beam computed tomography (CBCT). This imaging method provides detailed and accurate three-dimensional images with a low radiation dose, allowing an accurate assessment of enamel thickness. The analysis aims to identify variations in enamel thickness depending on the age and different levels of the labial tooth surface. Methods: 800 CBCT scans performed for diagnostic or therapeutic purposes on patients aged 18–60 years were analyzed. The data were gathered from the imaging archives of private practitioners from Targu Mures and the "George Emil Palade" University of Medicine, Pharmacy, Science, and Technology of Targu Mures. Enamel thickness measurements were conducted using the OnDemand3D Communicator CBCT evaluation program, with subsequent statistical analysis performed using GraphPad Instat Prism software. Results: Results showed significant variation in enamel thickness between the incisal, middle, and cervical segments of the labial surface of the upper central incisors. A decrease in enamel thickness with age has been observed. In patients aged 18–40, mean values of enamel thickness 1 mm and 3 mm above the cementoenamel junction (CEJ) were 0.48 ± 0.092, respectively, 0.819 ± 0.158. In patients over 40, the mean values were 0.454 ± 0.116 and 0.751 ± 0.067 at 1 mm, respectively, 3 mm above the CEJ. Statistically significant differences were found between the two age groups at 1 mm and 3 mm above the CEJ, with p < 0.0001 and p = 0.0214. Conclusions: A statistically significant decrease can be observed in enamel thickness in almost the entire labial surface of the upper central incisors with aging. The varied thickness of the enamel at different tooth levels requires individualized planning for each patient to maximize the long-term aesthetic and functional results. [ABSTRACT FROM AUTHOR]

Pogátsa Zoltán (2022): A globális elit. Kossuth Kiadó, Budapest, 319 oldal

Background: Intraoral scanning technology has opened new perspectives in dental practice, and combined with CAD/CAM technology, contributes significantly to fabricating high-quality prosthetic restorations. Our in vitro study aims to assess the accuracy of digital models obtained from one laboratory and two less commonly used intraoral scanners by conducting 3D measurements on the digital models obtained. Methods: An articulated simulator cast was used. Forty-eight scans were performed before and after tooth preparation with each scanner. The Zeiss Inspect software (Version: 2023.3.0.969) was used for measurements in sagittal and transversal planes. The obtained values were compared to reference values resulting from manual measurements. Results: Digital impressions provided discrepancies compared to the reference model. The lowest differences at the A2-L2 (the diagonal dimension of the models from the distal fossa of the second right maxillary molar and the maximum oral convexity of the artificial gingiva at the first left premolar) and the A1-B1 (transversal dimension of the model in the posterior area, from the right second molar's occlusal central fossa to the left second molar central fossa) distances were obtained for the upper models, and at the a1-b1 distance for all the lower models, except the non-prepared models scanned with the intraoral scanners (the discrepancies were not statistically significant). The discrepancies increased with the distance from the starting point of the scan. Conclusion: The number and position of prepared teeth can influence the accuracy of the scans. Distortions can appear in the case of multiple preparations. The scanning protocol and calibration must be optimized for the highest accuracy. Furthermore, in vivo studies are necessary to evaluate the clinical applicability of these findings. [ABSTRACT FROM AUTHOR]

Introduction: In Hungary, where MMR vaccine coverage is 99%, in 2017, a minor measles epidemic started from imported cases due to two major factors – latent susceptible cohorts among the domestic population and the vicinity of measles-endemic countries. Suspended immunization activities due to the COVID-19 surge are an ominous precursor to a measles resurgence. This epidemiological demonstration is aimed at promoting a better public understanding of epidemiological data. Materials and Methods: Our previous MMR sero-epidemiological measurements (N of total measles cases = 3919, N of mumps cases = 2132, and N of rubella cases = 2132) were analyzed using open-source epidemiological data (ANTSZ) of a small-scale measles epidemic outbreak (2017, Hungary). A simplified SEIR model was applied in the analysis. Results: In case of measles, due to a cluster-specific inadequacy of IgG levels, the cumulative seropositivity ratios (measles = 89.97%) failed to reach the herd immunity threshold (HIT Measles = 92–95%). Despite the fact that 90% of overall vaccination coverage is just slightly below the HIT, unprotected individuals may pose an elevated epidemiological risk. According to the SEIR model, ≥74% of susceptible individuals are expected to get infected. Estimations based on the input data of a local epidemic may suggest an even lower effective coverage rate (80%) in certain clusters of the population. Conclusion: Serological survey-based, historical and model-computed results are in agreement. A practical demonstration of epidemiological events of the past and present may promote a higher awareness of infectious diseases. Because of the high R0 value of measles, continuous large-scale monitoring of humoral immunity levels is important.

CCL20 is the only chemokine ligand for the chemokine receptor CCR6, which is expressed by the critical antigen presenting cells, dendritic cells. Increased expression of CCL20 is likely involved in the increased recruitment of dendritic cells observed in fibroinflammatory diseases such as chronic obstructive pulmonary disease (COPD). CCL20 expression is increased by the proinflammatory cytokine IL-1β. We have determined that IL-1β-dependent CCL20 expression is also dependent on the multifunctional cytokine TGF-β. TGF-β is expressed in a latent form that must be activated to function, and activation is achieved through binding to the integrin αvβ8 (itgb8). Here we confirm correlative increases in αvβ8 and IL-1β with CCL20 protein in lung parenchymal lysates of a large cohort of COPD patients. How IL-1β- and αvβ8-mediated TGF-β activation conspire to increase fibroblast CCL20 expression remains unknown, because these pathways have not been shown to directly interact. We evaluate the 5'-flanking region of CCL20 to determine that IL-1β-driven CCL20 expression is dependent on αvβ8-mediated activation of TGF-β. We identify a TGF-β-responsive element (i.e. SMAD) located on an upstream enhancer of the human CCL20 promoter required for efficient IL-1β-dependent CCL20 expression. By chromatin immunoprecipitation, this upstream enhancer complexes with the p50 subunit of NF-κB on a NF-κB-binding element close to the transcriptional start site of CCL20. These interactions are confirmed by electromobility shift assays in nuclear extracts from human lung fibroblasts. These data define a mechanism by which αvβ8-dependent activation of TGF-β regulates IL-1β-dependent CCL20 expression in COPD.

Transient Receptor Potential Vanilloid 1 (TRPV1) is a nonselective cation channel expressed by pain-sensing neurons and has been an attractive target for the development of drugs to treat pain. Recently, Src homology region two domain-containing phosphatase-1 (SHP-1, encoded by Ptpn6) was shown to dephosphorylate TRPV1 in dorsal root ganglia (DRG) neurons, which was linked with alleviating different pain phenotypes. These previous studies were performed in male rodents only and did not directly investigate the role of SHP-1 in TRPV-1 mediated sensitization. Therefore, our goal was to determine the impact of Ptpn6 overexpression on TRPV1-mediated neuronal responses and capsaicin-induced pain behavior in mice of both sexes. Twelve-week-old male and female mice overexpressing Ptpn6 (Shp1-Tg) and their wild type (WT) littermates were used. Ptpn6 overexpression was confirmed in the DRG of Shp1-Tg mice by RNA in situ hybridization and RT-qPCR. Trpv1 and Ptpn6 were found to be co-expressed in DRG sensory neurons in both genotypes. Functionally, this overexpression resulted in lower magnitude intracellular calcium responses to 200 nM capsaicin stimulation in DRG cultures from Shp1-Tg mice compared to WTs. In vivo, we tested the effects of Ptpn6 overexpression on capsaicin-induced pain through a model of capsaicin footpad injection. While capsaicin injection evoked nocifensive behavior (paw licking) and paw swelling in both genotypes and sexes, only WT mice developed mechanical allodynia after capsaicin injection. We observed similar level of TRPV1 protein expression in the DRG of both genotypes, however, a higher amount of tyrosine phosphorylated TRPV1 was detected in WT DRG. These experiments suggest that, while SHP-1 does not mediate the acute swelling and nocifensive behavior induced by capsaicin, it does mediate a protective effect against capsaicin-induced mechanical allodynia in both sexes. The protective effect of SHP-1 might be mediated by TRPV1 dephosphorylation in capsaicin-sensitive sensory neurons of the DRG. [ABSTRACT FROM AUTHOR]

MicroRNAs are short non-coding RNA molecules that are involved in tumor development and are considered to be promising candidates in cancer therapy. Here, we studied the role of miR-30s in the pathophysiology of ovarian cancer. According to our results miR-30a-5p, miR-30d-5p, and miR-30e-5p were overexpressed in the estrogen receptor α (ERα)-expressing PEO1 cell line compared to A2780 that lacks this receptor. Furthermore, the expression of miR-30a-5p, miR-30d-5p, and miR-30e-5p were induced in response to high-dose estrogen treatment in PEO1 where intensive cell death was observed according to the induction of apoptosis and autophagy. Lacking or blocking ERα function reduced tolerance to high-dose estrogen that suggests the importance of ERα-mediated estrogen response in the maintenance of proliferation. MiR-30d-5p mimic reduced cell proliferation in both A2780 and PEO1. Furthermore, it decreased the tolerance of PEO1 cells to high-dose estrogen by blocking the ERα-mediated estrogen response. This was accompanied by decreased SOX4 expression that is thought to be involved in the regulation of the PI3K/AKT pathway. Blocking this pathway by AZD8835 led to the same results. MiR-30d-5p or AZD8835 sensitized PEO1 cells to tamoxifen. We suggest that miR-30d-5p might be a promising candidate in the therapy of ovarian cancer.

This article deals with the role of internship programmes in encouraging young graduates from higher education to stay in their home region and is based on the findings of a questionnaire survey conducted in 2017. The aim of our research was to get a close view of the intern’s motivation and of their satisfaction; futhermore, whether they would like to work for the company and thanks to that stay in the region. Survey findings show that 56 percent of the respondents feel it is important to be employed close to their home, and 80 percent of the interns would like to work in a full-time position as soon as possible and aim to stay the company after the internship programme. These results would suggest that the internship programmemes of the multinational companies help to encourage young graduates to stay in their home region.

Abstract Background Spirocerca lupi is a parasitic nematode of canids that can lead to a severe and potentially fatal disease. Recently, a new species, Spirocerca vulpis, was described from red foxes in Europe, suggesting a high genetic diversity of the Spirocerca spp. infecting canids. The genetic variation and phylogenetic relationships of S. lupi collected from naturally-infected domestic dogs from Australia, Hungary, Israel, Italy, India and South Africa, and S. vulpis from red foxes from Bosnia and Herzegovina, Italy and Spain, was studied using mitochondrial and rDNA markers. Results A high intra-individual variation was found in the first internal transcribed spacer (ITS1) locus in all Spirocerca spp., ranging between 0.37–2.84%, with up to six haplotypes per specimen. In addition, a combination of phylogenetic and haplotype analyses revealed a large variability between S. lupi specimens collected from different geographical locations using the ITS1 (0.37–9.33%) and the cytochrome c oxidase subunit 1 (cox1) gene (1.42–6.74%). This genetic diversity led to the identification of two S. lupi genotypes circulating among dogs (PTP support > 0.829), including genotype 1 found in S. lupi from Australia, India, Israel and South Africa, and genotype 2 represented by specimens from Hungary and Italy. These genotypes presented pairwise nucleotide distances of 0.14%, 8.06% and 6.48 ± 0.28% in the small rDNA subunit (18S), ITS1 and cox1 loci, respectively. Additionally, Nei’s genetic distance in the ITS1 showed a further subdivision of genotype 1 worms into 1A (Israel and South Africa) and 1B (Australia and India). A morphological analysis of the anterior and posterior extremities of genotype 1 and genotype 2 worms using scanning electron microscopy did not show any differences between the specimens, contrary to the morphological differences between S. lupi and S. vulpis. Conclusions These findings demonstrate the high genetic variability among Spirocerca spp. from different geographical locations, thereby expanding our understanding of the epidemiology, evolution and phylogenetic variability within the genus.

Rheumatoid arthritis (RA) and other autoimmune inflammatory diseases are examples of imbalances within the immune system (disrupted homeostasis) that arise from the effects of an accumulation of environmental and habitual insults over a lifetime, combined with genetic predispositions. This review compares current immunotherapies—(1) disease-modifying anti-rheumatic drugs (DMARDs) and (2) Janus kinase (JAK) inhibitors (jakinibs)—to a newer approach—(3) therapeutic vaccines (using the LEAPS vaccine approach). The Ligand Epitope Antigen Presentation System (LEAPS) therapies are capable of inhibiting ongoing disease progression in animal models. Whereas DMARDs ablate or inhibit specific proinflammatory cytokines or cells and jakinibs inhibit the receptor activation cascade for expression of proinflammatory cytokines, the LEAPS therapeutic vaccines specifically modulate the ongoing antigen-specific, disease-driving, proinflammatory T memory cell responses. This decreases disease presentation and changes the cytokine conversation to decrease the expression of inflammatory cytokines (IL-17, IL-1(α or β), IL-6, IFN-γ, TNF-α) while increasing the expression of regulatory cytokines (IL-4, IL-10, TGF-β). This review refocuses the purpose of therapy for RA towards rebalancing the immune system rather than compromising specific components to stop disease. This review is intended to be thought provoking and look forward towards new therapeutic modalities rather than present a final definitive report.

Copyright of Metszetek is the property of University of Debrecen and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location, and implants used, there are also a wide range of animal models described modeling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to (1) animal model considerations, (2) outcome measurements, and (3) imaging. [ABSTRACT FROM AUTHOR]