A shedding analysis after AAV8 CNS injection revealed fragmented viral DNA without evidence of functional AAV particles in mice.

Adeno-associated viruses (AAV) are commonly used in the scientific field due to their diverse application range. However, AAV shedding, the release of virions from the host organism, can impact the safety of AAV-based approaches. An increasing number of authorities require the characterization of vector shedding in clinical trials. Recently, shedding of transduced laboratory animals has also gained attention regarding the necessary disposal measures of their waste products. However, no explicit international regulations for AAV-shedding waste exist. Generating insights into shedding dynamics becomes increasingly relevant to help authorities develop adequate regulations. To date, knowledge of AAV vector shedding in mice is very limited. Moreover, confirmation of functional shed AAV particles in mice is missing. Therefore, we examined feces, urine, and saliva of mice after CNS injection with AAV2/8. It revealed the presence of viral DNA fragments via qPCR for up to 4 days after injection. To examine AAV functionality we performed nested PCR and could not detect full-length viral genomes in any but two collected feces samples. Furthermore, a functional infection assay did not reveal evidence of intact AAV particles. Our findings are supposed to contribute murine shedding data as a foundation to help establish still lacking adequate biosafety regulations in the context of AAV shedding.

DRAC 2022: A public benchmark for diabetic retinopathy analysis on ultra-wide optical coherence tomography angiography images.

We described a challenge named "DRAC - Diabetic Retinopathy Analysis Challenge" in conjunction with the 25th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2022). Within this challenge, we provided the DRAC datset, an ultra-wide optical coherence tomography angiography (UW-OCTA) dataset (1,103 images), addressing three primary clinical tasks: diabetic retinopathy (DR) lesion segmentation, image quality assessment, and DR grading. The scientific community responded positively to the challenge, with 11, 12, and 13 teams submitting different solutions for these three tasks, respectively. This paper presents a concise summary and analysis of the top-performing solutions and results across all challenge tasks. These solutions could provide practical guidance for developing accurate classification and segmentation models for image quality assessment and DR diagnosis using UW-OCTA images, potentially improving the diagnostic capabilities of healthcare professionals. The dataset has been released to support the development of computer-aided diagnostic systems for DR evaluation.

Immunoproteasome deficiency results in age-dependent development of epilepsy.

The immunoproteasome is a central protease complex required for optimal antigen presentation. Immunoproteasome activity is also associated with facilitating the degradation of misfolded and oxidized proteins, which prevents cellular stress. While extensively studied during diseases with increasing evidence suggesting a role for the immunoproteasome during pathological conditions including neurodegenerative diseases, this enzyme complex is believed to be mainly not expressed in the healthy brain. In this study, we show an age-dependent increase in polyubiquitination in the brains of wild-type mice, accompanied by an induction of immunoproteasomes, which was most prominent in neurons and microglia. In contrast, mice completely lacking immunoproteasomes (triple-knockout mice), displayed a strong increase in polyubiquitinated proteins already in the young brain and developed spontaneous epileptic seizures, beginning at the age of 6 months. Injections of kainic acid led to high epilepsy-related mortality of aged triple-knockout mice, confirming increased pathological hyperexcitability states. Notably, the expression of the immunoproteasome was reduced in the brains of patients suffering from epilepsy. In addition, the aged triple-knockout mice showed increased anxiety, tau hyperphosphorylation and degeneration of Purkinje cell population with the resulting ataxic symptoms and locomotion alterations. Collectively, our study suggests a critical role for the immunoproteasome in the maintenance of a healthy brain during ageing.

Bacteremia Prevention during Periodontal Treatment-An In Vivo Feasibility Study.

The link between periodontitis and systemic diseases has increasingly become a focus of research in recent years. In this context, it is reasonable-especially in vulnerable patient groups-to minimize bacteremia during periodontal treatment. The aim of the present in vivo feasibility study was to investigate the possibility of laser-based bacteremia prevention. Patients with stage III, grade B generalized periodontitis were therefore treated in a split-mouth design either with prior 445 nm laser irradiation before nonsurgical periodontal therapy or without. During the treatments, clinical (periodontal measures, pain sensation, and body temperature), microbiological (sulcus samples and blood cultures before, 25 min after the start, and 10 min after the end of treatment), and immunological parameters (CRP, IL-6, and TNF-α) were obtained. It was shown that periodontal treatment-related bacteremia was detectable in both patients with the study design used. The species isolated were Schaalia georgiae, Granulicatella adiacens, and Parvimonas micra. The immunological parameters increased only slightly and occasionally. In the laser-assisted treatments, all blood cultures remained negative, demonstrating treatment-related bacteremia prevention. Within the limitations of this feasibility study, it can be concluded that prior laser disinfection can reduce bacteremia risk during periodontal therapy. Follow-up studies with larger patient numbers are needed to further investigate this effect, using the study design presented here.

Effect of head-mounted displays on students' acquisition of surgical suturing techniques compared to an e-learning and tutor-led course: a randomized controlled trial.

BACKGROUND: Although surgical suturing is one of the most important basic skills, many medical school graduates do not acquire sufficient knowledge of it due to its lack of integration into the curriculum or a shortage of tutors. E-learning approaches attempt to address this issue but still rely on the involvement of tutors. Furthermore, the learning experience and visual-spatial ability appear to play a critical role in surgical skill acquisition. Virtual reality head-mounted displays (HMDs) could address this, but the benefits of immersive and stereoscopic learning of surgical suturing techniques are still unclear. MATERIAL AND METHODS: In this multi-arm randomized controlled trial, 150 novices participated. Three teaching modalities were compared: an e-learning course (monoscopic), an HMD-based course (stereoscopic, immersive), both self-directed and a tutor-led course with feedback. Suturing performance was recorded by video camera both before and after course participation (>26 h of video material) and assessed in a blinded fashion using the Objective Structured Assessment of Technical Skills (OSATS) Global Rating Score (GRS). Furthermore, the optical flow of the videos was determined using an algorithm. The number of sutures performed was counted, the visual-spatial ability was measured with the Mental Rotation Test (MRT), and courses were assessed with questionnaires. RESULTS: Students' self-assessment in the HMD-based course was comparable to that of the tutor-led course and significantly better than in the e-learning course ( P =0.003). Course suitability was rated best for the tutor-led course ( x̄ =4.8), followed by the HMD-based ( x̄ =3.6) and e-learning ( x̄ =2.5) courses. The median ΔGRS between courses was comparable ( P =0.15) at 12.4 (95% CI 10.0-12.7) for the e-learning course, 14.1 (95% CI 13.0-15.0) for the HMD-based course, and 12.7 (95% CI 10.3-14.2) for the tutor-led course. However, the ΔGRS was significantly correlated with the number of sutures performed during the training session ( P =0.002), but not with visual-spatial ability ( P =0.615). Optical flow ( R2 =0.15, P <0.001) and the number of sutures performed ( R2 =0.73, P <0.001) can be used as additional measures to GRS. CONCLUSION: The use of HMDs with stereoscopic and immersive video provides advantages in the learning experience and should be preferred over a traditional web application for e-learning. Contrary to expectations, feedback is not necessary for novices to achieve a sufficient level in suturing; only the number of surgical sutures performed during training is a good determinant of competence improvement. Nevertheless, feedback still enhances the learning experience. Therefore, automated assessment as an alternative feedback approach could further improve self-directed learning modalities. As a next step, the data from this study could be used to develop such automated AI-based assessments.

Infection of Endothelial Cells with Acinetobacter baumannii Reveals Remodelling of Mitochondrial Protein Complexes.

Acinetobacter baumannii is an antibiotic-resistant, Gram-negative pathogen that causes a multitude of nosocomial infections. However, pathogenicity mechanisms and the host cell response during infection remain unclear. In this study, we determined virulence traits of A. baumannii clinical isolates belonging to the most widely disseminated international clonal lineage, international cluster 2 (IC2), in vitro and in vivo. Complexome profiling of primary human endothelial cells with A. baumannii revealed that mitochondria, and in particular complexes of the electron transport chain, are important host cell targets. Infection with highly virulent A. baumannii remodelled assembly of mitochondrial protein complexes and led to metabolic adaptation. These were characterized by reduced mitochondrial respiration and glycolysis in contrast to those observed in infection with low-pathogenicity A. baumannii. Perturbation of oxidative phosphorylation, destabilization of mitochondrial ribosomes, and interference with mitochondrial metabolic pathways were identified as important pathogenicity mechanisms. Understanding the interaction of human host cells with the current global A. baumannii clone is the basis to identify novel therapeutic targets. IMPORTANCE Virulence traits of Acinetobacter baumannii isolates of the worldwide most prevalent international clonal lineage, IC2, remain largely unknown. In our study, multidrug-resistant IC2 clinical isolates differed substantially in their virulence potential despite their close genetic relatedness. Our data suggest that, at least for some isolates, mitochondria are important target organelles during infection of primary human endothelial cells. Complexes of the respiratory chain were extensively remodelled after infection with a highly virulent A. baumannii strain, leading to metabolic adaptation characterized by severely reduced respiration and glycolysis. Perturbations of both mitochondrial morphology and mitoribosomes were identified as important pathogenicity mechanisms. Our data might help to further decipher the molecular mechanisms of A. baumannii and host mitochondrial interaction during infection.

Lactate induces metabolic and epigenetic reprogramming of pro-inflammatory Th17 cells.

Increased lactate levels in the tissue microenvironment are a well-known feature of chronic inflammation. However, the role of lactate in regulating T cell function remains controversial. Here, we demonstrate that extracellular lactate predominantly induces deregulation of the Th17-specific gene expression program by modulating the metabolic and epigenetic status of Th17 cells. Following lactate treatment, Th17 cells significantly reduced their IL-17A production and upregulated Foxp3 expression through ROS-driven IL-2 secretion. Moreover, we observed increased levels of genome-wide histone H3K18 lactylation, a recently described marker for active chromatin in macrophages, in lactate-treated Th17 cells. In addition, we show that high lactate concentrations suppress Th17 pathogenicity during intestinal inflammation in mice. These results indicate that lactate is capable of reprogramming pro-inflammatory T cell phenotypes into regulatory T cells.

Evaluation of an individual anamnesis tool for teaching risk-oriented prevention - a pilot study in undergraduate dental students.

BACKGROUND: A comprehensive medical history is needed to establish and ensure a high standard in dental care; however, it is challenging to draw clinical consequences on the variety of potential diseases and medications, especially for dental students. Aim of this observational study was to investigate, whether undergraduate dental students using an analog anamnesis tool for risk classification would be more confident and have more knowledge in risk classification than other students in the same year of study. METHODS: A cohort of 48 fifth year dental students was included and allocated into two groups based on their curriculum-related division (group A: n = 25, group B: n = 23). Group A received a teaching event and provision of an analog anamnesis tool for risk classification; group B received neither a teaching event nor the anamnesis tool. At baseline and after two weeks (follow-up), questionnaires regarding self-perceived confidence with risk classification, questions on different disease, medications and lifestyle factors and a task with 15 medical histories of prepared patient cases were applied. The data was statistically analyzed using Mann-Whitney or Wilcoxon test. RESULTS: In group comparison of the differences between baseline and follow-up regarding self-perceived confidence, significantly higher improvement was noted in group A compared to group B for all questions (p < 0.05). With regard to knowledge, the group comparison revealed that the differences in all of the four tasks were significantly higher in group A compared to group B (pi ≤ 0.01). Thereby, the different tasks in group A differed between baseline and follow-up as follows: Risk of complications: 49.04 ± 13.59 vs. 67.96 ± 17.22, p < 0.01, Risk of oral diseases: 48.77 ± 13.57 vs. 63.44 ± 16.78, p = 0.01, Indication of antibiotic prophylaxis: 75.70 ± 13.45 vs. 87.97 ± 10.37, p < 0.01 and the Medical history task on 15 patient cases: 58.45 ± 4.74 vs. 71.47 ± 9.54, p < 0.01. CONCLUSION: The applied analog anamnesis tool supported an increase in students´ confidence with issues related to at-risk patients alongside with their knowledge in risk classification. The applied anamnesis tool can be recommended for improving teaching of risk management for undergraduate dental students.

Cerebellar contribution to threat probability in a SCA6 mouse model.

Fear and anxiety have proven to be essential during the evolutionary process. However, the mechanisms involved in recognizing and categorizing threat probability (i.e. low to high) to elicit the appropriate defensive behavior are yet to be determined. In this study, we investigated the cerebellar contribution in evoking appropriate defensive escape behavior using a purely cerebellar, neurodegenerative mouse model for spinocerebellar ataxia type 6 which is caused by an expanded CAG repeat in exon 47 of the P/Q type calcium channel α1A subunit. These mice overexpress the carboxy terminus (CT) of the P/Q type calcium channel containing an expanded 27 CAG repeat specifically in cerebellar Purkinje cells (CT-longQ27PC). We found that our CT-longQ27PC mice exhibit anxiolytic behavior in the open field, elevated plus maze and light/dark place preference tests, which could be recovered with more threatening conditions such as brighter lighting, meowing sounds and an ultrasound repellent. Their innate fear to find safety in the Barnes maze and visual cliff tests was also diminished with subsequent trials, which could be partially recovered with an ultrasound repellent in the Barnes maze. However, under higher threat conditions such as in the light/dark place preference with ultrasound repellent and in the looming tests, CT-longQ27PC mice responded with higher defensive escape behaviors as controls. Moreover, CT-longQ27PC mice displayed increased levels of CT-labeled aggregates compared with controls. Together these data suggest that cerebellar degeneration by overexpression of CT-longQ27PC is sufficient to impair defensive escape responses in those mice.

Knowledge of undergraduate dental students regarding management of caries lesions.

OBJECTIVES: Understanding of lifelong control of disease processes associated with caries and its management is an essential part of dental education. This study evaluated the dental students' knowledge of caries diagnosis and management using the International Caries Classification and Management System (ICCMS). METHODS: A survey was conducted among undergraduate dental students at two dental schools, attending the sixth (centre 1) and seventh semester (centre 2), respectively. Medical histories, clinical images and radiographs of 12 patients were compiled as anonymous cases. For each case, a specific lesion was to be assessed. In addition, the students should determine the patient's caries risk and select a treatment option. An expert report (consensus decision) was used as the reference standard. For statistical analysis, kappa statistics and binomial tests were used. RESULTS: A total of 46 students participated in this study. The percentage of agreement of responses to the reference was: centre 1: 40.7-51.3%, centre 2: 57.9-67.9%. The corresponding Kappa values were: centre 1: 0.073-0.175, centre 2: 0.315-0.432. Overall, students tended to underestimate the codes compared to the reference standard (p < 0.001). CONCLUSION: Introducing systematic content about caries diagnosis and management such as ICDAS and ICCMS in the learning objectives of undergraduate dental students can be proposed. However, in order to improve diagnosis and enable a more reliable choice of treatment options, attention should also be given to the way they are didactically taught.

The Role of Immunoproteasomes in Tumor-Immune Cell Interactions in Melanoma and Colon Cancer.

The participation of proteasomes in vital cellular and metabolic processes that are involved in tumor growth has made this protease complex an attractive target for cancer treatment. In contrast to ubiquitously available constitutive proteasome, the increased enzymatic activity of immunoproteasome is associated with tumor-infiltrating immune cells, such as antigen-presenting cells and T lymphocytes. In various tumors, an effective anti-tumor immunity is provided through generation of tumor-associated antigens by proteasomes, contributing crucially to cancer eradication by T lymphocytes. The knowledge regarding the role of immunoproteasomes in the communication between tumor cells and infiltrating immune cells is limited. Novel data suggest that the involvement of immunoproteasomes in tumorigenesis is more complex than previously thought. In the intestine, in which diverse signals from commensal bacteria and food can contribute to the onset of chronic inflammation and inflammation-driven cancer, immunoproteasomes exert tumorigenic properties by modulating the expression of pro-inflammatory factors. In contrast, in melanoma and non-small cell lung cancer, the immunoproteasome acts against cancer development by promoting an effective anti-tumor immunity. In this review, we highlight the potential of immunoproteasomes to either contribute to inflammatory signaling and tumor development, or to support anti-cancer immunity. Further, we discuss novel therapeutic options for cancer treatments that are associated with modulating the activity of immunoproteasomes in the tumor microenvironment.

A video- and feedback-based approach to teaching communication skills in undergraduate clinical dental education: The student perspective.

OBJECTIVE: Student evaluation of a communication-education programme that combined patient consultation videos with peer- or expert-based feedback. METHODS: A self-perception questionnaire was given to undergraduate dental students who had undertaken a curricular communication training and feedback programme, in which each participant was videoed three times during a patient interview or consultation, subsequently receiving either peer (PG) or expert feedback (EG). The questionnaire used feedback programme content to evaluate student perspectives, ascertaining whether the students experienced a gain in knowledge and professional conversational skills, whether videos or feedback helped them improve more and general questions about the structure and content of the curriculum. Differences between feedback groups were analysed (Mann-Whitney U test). RESULTS: 45 participants (peer group: n = 23, expert group: n = 22) took part in the study. The peer group experienced watching their video (38%) and receiving feedback (33%) as their major beneficial aspect to improve communication skills (watching fellow student´s video: 17%, providing feedback: 12%). The expert group experienced the major effect in receiving expert feedback (73%, video watching: 27%). The students said that communication skills should be a core competency in dental education learning outcomes (PG: 4.48 ± 0.67, EG: 4.41 ± 0.67; P > 0.05) and that communication curricula should include video-based feedback (PG: 3.91 ± 0.73, EG: 4.00 ± 0.93; P > 0.05). CONCLUSION: Watching videos and both receiving and providing peer group feedback were experienced as helpful in improving students' communication skills. These findings suggest that a longitudinal communication curriculum, which includes both video-based peer feedback and correlated self-reflection, is a promising learning approach for dental education.

STAndard Reporting of CAries Detection and Diagnostic Studies (STARCARDDS).

AIM: The aim of this paper is to present recommendations from an international workshop which evaluated the methodology and reporting of caries diagnostic studies. As a unique feature, this type of studies is focused on caries lesion detection and assessment, and many of them are carried out in vitro, because of the possibility of histological validation of the whole caries spectrum. This feature is not well covered in the existing reporting STARD guideline within the EQUATOR Network. PARTICIPANTS AND METHODS: An international working group of 13 cariology researchers was formed. The STARD checklist was reviewed and modified for caries detection and diagnosis purposes, in a three-step process of evaluation, consensual modification, and delivery during three 2-day workshops over 18 months. Special attention was paid to reporting requirements of caries studies that solely focus on reliability. RESULTS: The STARD checklist was modified in 14/30 items, with an emphasis on issues of sample selection (tooth selection in in vitro studies), blinding, and detailed reporting of results. CONCLUSION: Following STARCARDDS (STAndard Reporting of CAries Detection and Diagnostic Studies) is expected to result in complete reporting of study design and methodology in future caries diagnosis and detection experiments both in vivo and in vitro, thus allowing for better comparability of studies and higher quality of systematic reviews. CLINICAL RELEVANCE: Standardization of caries diagnostic studies leads to a better comparability among future studies, both in vivo and in vitro.

Arrest of root caries with an adjuvant chlorhexidine-fluoride varnish over a 12-months observation period: a QLF-analyzed, placebo-controlled, randomized, clinical trial (RCT).

This study aimed at evaluating the effectiveness of an adjuvant chlorhexidine-fluoride varnish (Cervitec F) for prevention and arrest of root caries on elderly participants using quantitative light-induced fluorescence (QLF). 23 participants with two or three non-cavitated root carious lesions were included and assigned to three groups of different varnishes (CF: Cervitec F, P: placebo, DP: Duraphate). Agents were applied once to root surface at baseline and in follow-up after 3, 6 and 9 months. The lesions were assessed clinically and with QLF. QLF-images were analyzed regarding fluorescence loss (ΔF), lesion volume (ΔQ) and bacterial activity (ΔR) before (t0), after 14 days (t1), 6- (t2) and 12-months (t3). CF showed a significant difference between t0 and t3: ∆F (- 12.51 [15.41] vs. - 7.80 [16.72], p = 0.012), ∆Q (- 2339.97 (20,898.30) vs. - 751.82 (5725.35), p < 0.001), ∆R (23.80 [41.70] vs. 7.07 [37.50], p = 0.006). Independently of the varnish application, preventive care seems positively influence the root caries progress. Although within CF group the strongest effect was observed, no superiority of a specific varnish application was confirmed over a 12-months QLF observation period. Extra topical fluoride can help remineralise dentin lesions and QLF can be used as a measurement method to determine changes in the dentin lesions.

Antimicrobial Impact of Different Air-Polishing Powders in a Subgingival Biofilm Model.

Subgingival air-polishing devices (SAPD) can reduce bacterial biofilms and thus support periodontal healing. The authors of this study evaluated the effectiveness of the glycine-based and trehalose-based air-polishing powders in removing pathogenic bacteria in a subgingival biofilm model. We treated 56 subgingival pockets in porcine jaws with SAPD. Subgingival air polishing was performed in three groups of 13 pockets each: I, glycine-based powder; II, trehalose-based powder; and III, water alone. Another group (IV) served as untreated controls. Prior to air polishing, inoculated titanium bars were inserted into the pockets containing periopathogenic bacteria such as Porphyromonas gingivalis and Tannerella forsythia. Remaining bacteria were evaluated using real-time PCR. The numbers of remaining bacteria depended on the treatment procedure, with the lowest number of total bacteria in group I (median: 1.96 × 106 CFU; min: 1.46 × 105; max: 9.30 × 106). Both polishing powders in groups I and II (median: 1.36 × 107 CFU; min: 5.22 × 105; max: 7.50 × 107) showed a statistically significantly lower total bacterial load in comparison to both group IV (median: 2.02 × 108 CFU; min: 5.14 × 107; max: 4.51 × 108; p < 0.05) and group III (median: 4.58 × 107 CFU; min: 2.00 × 106; max: 3.06 × 108; p < 0.05). Both subgingival air-polishing powders investigated can reduce periopathogenic bacteria and thus support antimicrobial therapy approaches in periodontal treatment regimens.

Systematic review and meta-analysis of diagnostic studies of proximal surface caries.

AIM: This systematic review and meta-analysis aimed to assess the diagnostic accuracy and reliability of commonly used caries detection methods for proximal caries diagnostics. Visual examination (VE), bitewing radiography (BWR), laser fluorescence (LF), and fibre-optic transillumination (FOTI) were considered in detail. MATERIAL AND METHODS: PRISMA guidelines for the reporting of systematic reviews and meta-analyses were applied. The mnemonic PIRDS (problem, index test, reference test, diagnostic and study type) concept was used to guide the literature search. Next, studies that met the inclusion criteria were stepwise selected and evaluated for their quality with a risk of bias (RoB) assessment tool. Studies with low/moderate bias and sufficient reporting were considered for meta-analysis. The pooled sensitivity (SE), specificity (SP), diagnostic odds ratio (DOR), and area under the ROC curve (AUC) were calculated. RESULTS: From 129 studies meeting the selection criteria, 31 in vitro studies and five clinical studies were finally included in the meta-analysis. The AUC values for in vitro VE amounted to 0.84 (caries detection) and 0.85 (dentin caries detection). BWR ranged in vitro from 0.55 to 0.82 (caries detection) and 0.81-0.92 (dentin caries detection). LF showed higher AUC values for overall caries detection (0.91) and dentin caries detection (0.83) than did other methods. Clinical data are limited. CONCLUSION: The number of diagnostic studies with low/moderate RoB was found to be low and indicates a need for high-quality, well-designed caries diagnostic studies. CLINICAL RELEVANCE: BWR and LF showed good diagnostic performance on proximal surfaces. However, because of the low number of includable clinical studies, these data should be interpreted with caution.

Identifying and Avoiding Risk of Bias in Caries Diagnostic Studies.

Caries diagnostic studies differ with respect to their design, included patients/tooth samples, use of diagnostic and reference methods, calibration, blinding and data reporting. Such heterogeneity makes comparisons between studies difficult and could represent a substantial risk of bias (RoB) when it is not identified. Therefore, the present report aims to describe the development and background of a RoB assessment tool for caries diagnostic studies. The expert group developed and agreed to use a RoB assessment tool during three workshops. Here, existing instruments (e.g., QUADAS 2 and the Joanna Briggs Institute Reviewers' Manual) influenced the hierarchy and phrasing of the signalling questions that were adapted to the specific dental purpose. The tailored RoB assessment tool that was created consists of 16 signalling questions that are organized in four domains. This tool considers the selection/spectrum bias (1), the bias of the index (2) and reference tests (3), and the bias of the study flow and data analysis (4) and can be downloaded from the journal website. This paper explores possible sources of heterogeneity and bias in caries diagnostic studies and summarizes the relevant methodological aspects.

Systematic review and meta-analysis of diagnostic methods for occlusal surface caries.

AIM: This systematic review and meta-analysis aimed to assess the diagnostic performance of commonly used methods for occlusal caries diagnostics, such as visual examination (VE), bitewing radiography (BW) and laser fluorescence (LF), in relation to their ability to detect (dentin) caries under clinical and laboratory conditions. MATERIALS AND METHODS: A systematic search of the literature was performed to identify studies meeting the inclusion criteria using the PIRDS concept (N = 1090). A risk of bias (RoB) assessment tool was used for quality evaluation. Reports with low/moderate RoB, well-matching thresholds for index and reference tests and appropriate reporting were included in the meta-analysis (N = 37; 29 in vivo/8 in vitro). The pooled sensitivity (SE), specificity (SP), diagnostic odds ratio (DOR) and areas under ROC curves (AUCs) were computed. RESULTS: SP ranged from 0.50 (fibre-optic transillumination/caries detection level) to 0.97 (conventional BW/dentine detection level) in vitro. AUCs were typically higher for BW or LF than for VE. The highest AUC of 0.89 was observed for VE at the 1/3 dentin caries detection level; SE (0.70) was registered to be higher than SP (0.47) for VE at the caries detection level in vivo. CONCLUSION: The number of included studies was found to be low. This underlines the need for high-quality caries diagnostic studies that further provide data in relation to multiple caries thresholds. CLINICAL RELEVANCE: VE, BW and LF provide acceptable measures for their diagnostic performance on occlusal surfaces, but the results should be interpreted with caution due to the limited data in many categories.

OXA-484, an OXA-48-Type Carbapenem-Hydrolyzing Class D ß-Lactamase From Escherichia coli.

OXA-48-like carbapenemases are among the most frequent carbapenemases in Gram-negative Enterobacterales worldwide with the highest prevalence in the Middle East, North Africa and Europe. Here, we investigated the so far uncharacterized carbapenemase OXA-484 from a clinical E. coli isolate belonging to the high-risk clone ST410 regarding antibiotic resistance pattern, horizontal gene transfer (HGT) and genetic support. OXA-484 differs by the amino acid substitution 214G compared to the most closely related variants OXA-181 (214R) and OXA-232 (214S). The bla OXA - 484 was carried on a self-transmissible 51.5 kb IncX3 plasmid (pOXA-484) showing high sequence similarity with plasmids harboring bla OXA - 181. Intraspecies and intergenus HGT of pOXA-484 to different recipients occurred at low frequencies of 1.4 × 10-7 to 2.1 × 10-6. OXA-484 increased MICs of temocillin and carbapenems similar to OXA-232 and OXA-244, but lower compared with OXA-48 and OXA-181. Hence, OXA-484 combines properties of OXA-181-like plasmid support and transferability as well as ß-lactamase activity of OXA-232.

OCT evaluation of the internal adaptation of ceramic veneers depending on preparation design and ceramic thickness.

OBJECTIVES: In-vitro evaluation of the influence of preparation design and thickness of ceramic veneers on the interfacial bond using optical coherence tomography (OCT). METHODS: Sixty-four central incisors were randomly assigned to four preparation designs differing from no to complete dentine exposure (n = 16 each): non-prep (NP), minimal-invasive (MI, no dentine exposure), semi-invasive (SI, 50% dentine) and invasive (I, 100% dentine). Ceramic veneers (IPS InLine Veneer) of two thicknesses (0.2-0.5 mm (T1) and > 0.5-1.2 mm (T2)) were etched, silanized, and adhesively luted (Optibond FL, Variolink Veneer). After water storage (37 °C, 21d), thermocycling (2000 cycles, 5°-55 °C), and mechanical loading (2 + 1 million cycles, 50 + 100 N) specimens were imaged by spectral-domain OCT (Telesto II, Thorlabs). Adhesive defects at the ceramic-composite and tooth-composite interfaces were quantified on 35 equidistantly distributed OCT B-scans (length, %). Statistical differences were verified with Wilcoxon-/Mann-Whitney-U-test (α = 0.05). RESULTS: Adhesive defects appeared in all groups at both interfaces, albeit to differing extents (0.1 - 31.7%). NP and MI veneers showed no significant differences at the interfaces (pi > 0.05). In groups, SI and I, significantly more adhesive defects appeared at the tooth-composite compared to the veneer-composite interface (pi ≤ 0.039). The following preparation designs and veneer thicknesses showed differences (pi ≤ 0.021): Veneer-composite: NP-T1 < I-T1, MI-T1 < I-T1, I-T1 > I-T2; Tooth-composite: NP-T1 < SI-T1, NP-T1 < I-T1, NP-T2 > MI-T2, MI-T1 < SI-T1, MI-T1 < I-T1, SI-T1 < I-T1, MI-T2 < SI-T2, MI-T2 < I-T2. SIGNIFICANCE: The interface adhesion of ceramic veneers was influenced by the preparation design and the veneer thickness. A ceramic thickness of at least 0.5 mm and a preparation without exposing dentine is advantageous for the interfacial bond.