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Abstract Tooth degradation develops easily over time from initial caries to deeper cavities. The quality and durability of restorations are crucial in a patients’ life, and it is primarily determined by the mechanical properties of the restorations. Clinicians and engineers apply biomimetic science in dentistry to mimic the natural design of the teeth and emphasize careful material selection as well as bond strength between the tissue and artificial material. The aim of this research was to develop and compare five different bulk filling restoration techniques for high C-factor (5.0) Class I cavities and determine the most durable technique. Tensile bond strength between the dentin and the filling, as well as the inner structure of the filling was measured via computed tomography, scanning electron microscopy and mechanical testing methods. It was found that the semi-direct bulk filling technique (bulk filling with an extra, indirect curing step) can increase the tensile bond strength on average by 58% (51.1 ± 12.2 MPa) compared to the direct bulk filling method with the same materials (32.4 ± 8.2 MPa). The introduced semi-direct technique allows bulk filling to be used on Class I cavities while achieving a high bond strength, resulting in highly durable and reproducible restorations.

Globally, the incidence of obesity among adults has significantly risen since 1990, with a more than twofold rise in prevalence. Similarly, the incidence of obesity among adolescents has increased fourfold. Overweight constitutes a significant health and social issue in developed nations globally. Conventional therapies such as lifestyle modification (nutrition and physical activity) have limited weight reduction. Drug therapy is often not possible or cannot be afforded due to poor patient compliance or therapeutic side effects.20-hydroxyecdysone (20E) is a worldwide used ‘green anabolic’ dietary supplement that has beneficial effects in some animal models of metabolic diseases. Our ongoing research examines the impacts of 20E and calonysterone (CAL) in an animal model with a diet high in fats and sugars (HFHSD).Glucose tolerance tests assessed prediabetic status and RT-PCR and Western blot analysis determined interleukin-6 (IL6) expression. The concertations of superoxide dismutase, catalase, adiponectin, leptin, and IL-6 were quantified by ELISA. Total antioxidant capacity was assessed using a colorimetric assay kit, and global DNA methylation was also measured.CAL entirely prevented HFHSD-induced obesity and decreased the inflammatory cytokine (IL6) level and antioxidant activity in our model. Both 20E and CAL normalized the changed plasma concentration of adiponectin and leptin after the HFHS diet. The administration of CAL and 20E in obese rats significantly increased the percent of total DNA methylation.This is the first in vivo study on this natural ecdysteroid, which may offer new alternatives for treating metabolic diseases. Based on our findings, we are supposed to show new preventive possibilities for overweight-induced chronic progressive diseases.

Summary: Background: Timely management of sepsis with early targeted antimicrobial therapy improves patient outcomes. Rapid molecular assays (RMAs) have emerged, enabling the detection of bloodstream infection (BSI) with a shorter turnaround time than blood cultures (BCs). The accuracy of several RMAs has not been comprehensively reviewed. We aimed to identify commercial RMAs reported in the literature and evaluate their diagnostic performance compared to BC. Methods: A systematic review and meta-analysis was conducted, covering MEDLINE, Cochrane Library, Embase, and Web of Science from inception to September 23, 2024. Eligible studies included patients with suspected or documented BSI, tested with both an RMA (turnaround time of ≤12 h, targeting ≥20 pathogens) and BC. Non-original research articles and animal studies were excluded. The primary outcomes were pooled sensitivity and specificity of RMAs for pathogen detection compared to BC. Bivariate analysis was used to produce summary receiver operating characteristic plots and diagnostic metric measures stratified by different units of analysis (sample versus patient), RMA types, and patient populations. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C) tools. The study was registered with PROSPERO, CRD42022377280. Findings: A total of 63,916 articles were identified, of which 104 were included in the qualitative synthesis and 75 in the quantitative synthesis, covering 17,952 samples and 11,393 patients analyzed separately. Eleven RMAs were identified, with four included in the RMA-based subgroup analysis (LightCycler SeptiFast Test MGRADE®, IRIDICA BAC BSI assay, SepsiTest, MagicPlex Sepsis Test) and five additional ones in the pooled analysis (UMD-SelectNA, VYOO®, MicrobScan assay, MicrobScan-Kairos24/7, REBA Sepsis-ID test). Two RMAs were included in the qualitative synthesis only (InfectID-BSI, Pilot Gene Technology droplet digital polymerase chain reaction). Pooled specificity of RMAs was higher (0.858, 95% confidence interval (CI) 0.830–0.883) than sensitivity (0.659, 95% CI 0.594–0.719) by patient. Sensitivities varied by RMA type from 0.492 (95% CI 0.390–0.594, MagicPlex Sepsis Test) to 0.783 (95% CI 0.662–0.870, IRIDICA BAC BSI assay) by patient. Specificities varied more by patient population, ranging from 0.811 (95% CI 0.716–0.879) in the intensive care population to 0.892 (95% CI 0.838–0.930) in the emergency department population, by patient. Similar metrics were observed when the analysis was done by sample. Risk of bias was judged to be high in all included articles. Interpretation: Despite their shorter turnaround time, low sensitivity means RMAs cannot replace BCs. However, our data indicate that RMAs may have value as an add-on test by increasing pathogen detection rates. Higher-sensitivity RMAs are needed which could possibly be achieved by expanding pathogen coverage and increasing blood sample volumes. High-quality implementation studies and standardized reporting are required to assess the clinical advantages of RMAs. Funding: Centre for Translational Medicine, Semmelweis University.

Objectives: To investigate the effects of doxycycline pre- and post-exposure prophylaxis (doxy-PrEP/PEP) on bacterial sexually transmitted infections (STIs) by conducting a systematic review and meta-analysis. Methods: PubMed, Embase, and CENTRAL were searched for randomized controlled trials (RCTs), including ongoing studies published until November 7, 2023. Our primary endpoint was the incidence of bacterial STIs measured as the number of visits with an STI per total number of visits. Random-effects model was used to estimate pooled effect sizes. The study was registered with PROSPERO, CRD42023478486. Results: We identified six eligible studies containing data from seven articles and four conference abstracts, enrolling men who have sex with men (MSM), transgender women (TGW), and cisgender women (CGW). The pooled analysis of 1,766 participants with 602 newly diagnosed STIs showed a 56% decrease in the overall STI incidence using doxy-PrEP/PEP (RR = 0.44; 95% CI: 0.30-0.65; I2 = 73%). For doxy-PEP, including MSM and TGW only, the RR observed for overall STI incidence was 0.40 (95% CI: 0.28-0.57; I² = 37%), 0.19 (95% CI: 0.08-0.44; I² = 39%) for chlamydia, 0.23 (0.14-0.36; I² = 0%) for syphilis and 0.55 (95% CI: 0.34-0.87; I² = 41%) for gonorrhea. No serious adverse events were reported in the studies. The certainty of evidence regarding the efficacy of doxy-PEP among MSM and TGW was graded as high. Conclusion: Doxy-PEP significantly reduces the number of new cases of chlamydia and syphilis and is potentially effective against gonorrhea, influenced by local resistance patterns. Thus, it is a promising tool in the prevention of bacterial STIs among MSM and TGW.

Bimodal composite metal foams made from Al99.5 aluminium and quasi-eutectic Sr-modified AlSi12 matrix were investigated, where the bimodality was introduced by two alumina hollow sphere sets with nominal diameters of Ø7.0 and Ø2.4 mm in various volume concentrations. The research aimed to determine the effect of the cell structure (especially the unintended porosity) on the first compressive stress maximum, depending on the applied matrix material. The various features of the cell structure were quantitatively measured in composite metal foams by filtering raw computed tomography analysis data. The casting porosity, the wetting porosity, the porosity from the various-sized hollow spheres, and the partially matrix-filled hollow spheres have been successfully distinguished based on volumetric and geometrical conditions, such as sphericity and compactness. The unintended porosity (as the sum of the casting porosity and the wetting porosity) influences the first compressive stress maximum of the Al99.5 matrix composite metal foams. In contrast, for the AlSi12Sr bimodal foams, the results correlated with the total porosity values. The first compressive stress maximum could be estimated well from the compressive yield strength of the matrix and the total porosity of the foam.

Cells have evolved various DNA repair mechanisms to prevent DNA damage from building up. Malfunctions during DNA repair can influence cellular homeostasis because they can bring on genomic instability through the improper recognition of DNA damage or dysregulation of the repair process. Maintaining proper DNA repair is also essential for stem cells (SCs), as they provide a differentiated cell population to the living organism. SCs are regularly used in personalized stem cell therapy. Patients must be treated with specific activators to produce these SCs effectively. This report investigated the impact of treating mesenchymal stem cells (MSC) with lipopolysaccharide, tumor necrosis factor, interferon-gamma, polyinosinic acid, interleukin 1 beta, while monitoring their transcription-related response using next-generation sequencing. RNA sequencing revealed robust gene expression changes, including those of specific genes encoding proteins implicated in DNA damage response. Stem cells can effectively repair specific DNA damages; moreover, they fail to undergo senescence or cell death when genetic lesions accumulate. Here, we draw attention to an elevated DNA repair activation following MSC induction, which may be the main reason for the ineffective stem cell transplantation and may also contribute to the genetic drift that can initiate tumor formation.

Aquaporins (AQPs) are involved in the process of implantation, regulate myometrial contractions and cervical ripening, and maintain appropriate placental functioning. The molecular mechanism of these functions is not fully understood. Our study aimed to investigate the physiological significance of AQP5 during pregnancy and to determine the cooperation between the adrenergic system and the AQP5 in uterine contraction in the late-pregnant rat uterus.After administering AQP5 siRNA intraperitoneally to Sprague-Dawley rats, the length of the gestational period was determined and the changes in uterine contractions were measured in an isolated organ bath system. Pharmacological influence on AQP5 expression and uterine contraction was investigated by treatment with terbutaline (10 mg/kg, subcutaneously) and doxazosin (5 mg/kg, orally) in vivo; and mercuric chloride (HgCl2), in vitro. Moreover, the levels of cAMP response element binding protein (CREB) were measured in the uterus by an ELISA kit.The gestational period became shorter, AQP5 expression significantly decreased and rat uterus contraction increased after AQP5 siRNA treatment compared to the control. Treatment with terbutaline significantly increased AQP5 mRNA and protein expression after 30 min and continuously reduced it until 90 min, whereas doxazosin treatment did not significantly alter AQP5 expression. Treatment with the AQP5 antagonist HgCl2 increased spontaneous uterus contraction and decreased norepinephrine-induced uterus contraction with decreasing AQP5 expression in pregnant rat uterus. Moreover, the tocolytic effect through the adrenergic system was amplified in the presence of an AQP5 antagonist, presumably via the changes in cAMP level.In conclusion, our findings elucidate the collaborative role of aquaporin 5 (AQP5) and adrenergic systems in the regulation of uterine contractions in late-pregnant rats. Our findings suggest this may be a good starting point for developing a new tocolytic therapy.

Telemedicine brings several benefits to patients, healthcare providers, and the wider society, including reductions in the need for hospitalizations or readmissions, as well as in overall healthcare costs and the length of inpatient stay. In addition, these services may provide psychological benefits to patients, including excellent satisfaction and medication adherence. The present study aimed to investigate an in-house-developed otorhinolaryngologic remote diagnostic system (mobile app). The basis of the comparison was the incidence between the diagnoses and therapies made by remote diagnosticians and on-site specialists based on static images and videos captured by a smartphone otoscope device. In the study, 103 patients were involved. After registering demographic data, the telemedicine software was evaluated by comparing the matching of physically established diagnoses and/or therapies with remotely established diagnoses and/or therapies. The most remarkable result was in concordance with the diagnoses, with 79 matches identified of the 103 cases examined; the rate of the matching cases was 76.7% (95% CI: 68.5–84.9%). These results support that telemedicine-based otorhinolaryngological remote diagnostics could play a significant role in future healthcare.

IntroductionWhile Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy.MethodsEvaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders.ResultsSix proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort.DiscussionOur study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.

Abstract Background Livedoid vasculopathy (LV) and cutaneous arteritis (CA) are rare cutaneous diseases. A consideration of these two conditions as different entities is debatable, because thrombosis and inflammation are closely related in their pathogenesis mechanisms. Varying reports on the effectiveness of anticoagulant and immunosuppressant therapies in LV and CA also point to diagnostic challenge and overlap in these conditions. Objectives We sought to assess the therapeutic effect of anticoagulation therapy in adult patients with CA, who were recalcitrant to immunosuppressive modalities. Methods A monocentric retrospective analysis of adult patients who were diagnosed with CA between 2010 and 2018, was carried out. Results We describe 8 cases of long‐term recalcitrant CA, in whom anticoagulation therapy significantly reduced the pain and cutaneous symptoms. All patients had cutaneous symptoms compatible with CA along with clinical features also characteristic of LV, including underlying procoagulative disorders in the majority (87.5%), as confirmed by screening for thrombophilia. We also review current concepts regarding LV and CA, and suggest vascular occlusion is a common link between these two entities. Conclusions Although current knowledge advocates segregating vasculopathy from vasculitis by means of histopathological examination in LV and CA, clinical experience suggests some overlap and common complex underlying pathomechanisms.