Hepatitis B cure: Current situation and prospects.

Achievement of a 'clinical cure' in chronic hepatitis B (CHB) implies sustained virological suppression and immunological control over the infection, which is the ideal treatment goal according to domestic and international CHB management guidelines. Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens. These regimens incorporate either nucleos(t)ide analogs, immunomodulatory agents such as pegylated interferon α, or a strategic combination of both, sequentially or concurrently administered. Despite these advancements in the clinical handling of hepatitis B, achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes. These include, but are not limited to, the emergence of antiviral resistance, incomplete immune recovery, and the persistence of covalently closed circular DNA. Moreover, the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure. This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

Application of Mixture and Non-mixture Cure Models in Survival Analysis of Patients With COVID-19.

Background Due to the emergence of new COVID-19 mutations and an increase in re-infection rates, it has become an important priority for the medical community to identify the factors affecting the short- and long-term survival of patients. This study aimed to determine the risk factors of short- and long-term survival in patients with COVID-19 based on mixture and non-mixture cure models. Methodology In this study, the data of 880 patients with COVID-19 confirmed with polymerase chain reaction in Fereydunshahr city (Isfahan, Iran) from February 20, 2020, to December 21, 2021, were gathered, and the vital status of these patients was followed for at least one year. Due to the high rate of censoring, mixture and non-mixture cure models were applied to estimate the survival. Akaike information criterion values were used to evaluate the fit of the models. Results In this study, the mean age of the patients was 48.9 ± 21.23 years, and the estimated survival rates on the first day, the fourth day, the first week, the first month, and at one year were 0.997, 0.982, 0.973, 0.936, and 0.928, respectively. Among the parametric models, the log-logistic mixed cure model with the logit link, which showed the lowest Akaike information criterion value, demonstrated the best fit. The variables of age and prescribed medication type were significant predictors of long-term survival, while occupation was influential in the short-term survival of patients. Conclusions According to the results of this study, it can be concluded that elderly patients should observe health protocols more strictly and consider receiving booster vaccine doses. The log-logistic cure model with a logit link can be used for survival analysis in COVID-19 patients, a fraction of whom have long-term survival.

[A simulation study of the reliability and accuracy of Cox-TEL method for estimating hazard ratio and difference in proportions for long-term survival data containing cured patients].

OBJECTIVE: To explore the applicable conditions of the Cox-TEL (Cox PH-Taylor expansion adjustment for long-term survival data) method for analysis of survival data that contain cured patients. METHODS: The simulated survival data method based on Weibull distribution was used to simulate and generate the survival data with different cure rates, censored rates, and cure rate differences. The Cox-TEL method was used for analysis of the generated simulation data, and its performance was evaluated by calculating its type Ⅰ error and power. RESULTS: Almost all the type Ⅰ error of the hazard ratios (HRs) obtained by the Cox-TEL method under different conditions were slightly greater than 0.05, and this method showed a good test power for estimating the HRs for data with a large sample size and a large difference in proportions (DPs). For the data of cured patients, the type Ⅰ error of the DPs obtained by the Cox-TEL method was well around 0.05, and its test power was robust in most of the scenarios. CONCLUSION: The Cox-TEL method is effective for analyzing data of uncured patients and obtaining reliable HRs for most of the survival data with a sample size, a low censored rates, and a large difference in cure rates. The method is capable of accurately estimating the DPs regardless of the sample size, censored rates, or the cure rates.

Clinical Efficacy and Safety Meta-Analysis of Different Surgical Approaches for Female Stress Urinary Incontinence.

OBJECTIVE: Meta-analysis was conducted to compare and evaluate the efficacy and safety of tension-free vaginal tape (TVT), outside-in trans-obturator tape (TOT), inside-out tension-free vaginal tape-obturator (TVT-O) and transvaginal tension-free urethral sling surgery (TVT-S) in the treatment of female stress urinary incontinence (SUI). METHODS: A computer-based systematic search of the PubMed, The Cochrane Library, Medline, Embase, Web of Science and ScienceDirect databases for randomised controlled trials (RCTs) comparing TVT, TOT, TVT-O and TVT-S for the treatment of SUI was performed from the time of library construction to November 2023. Two investigators performed data extraction and quality evaluation of the included RCTs, extracting information including the follows: First author, time of publication, intervention, sample size, age, duration of follow-up and objective cure rate, subjective cure rate, dyspareunia, vaginal mucosal perforation, urinary tract infection, sling exposure and postoperative thigh pain/groin pain. Review Manager (RevMan) 5.4 was used for data processing. RESULTS: A total of 14 RCTs with 2665 patients were included. Meta-analysis showed no statistically significant differences in objective cure rate, urinary tract infection, sling exposure and postoperative thigh pain/groin pain. The subjective cure rate of TVT was higher than that of TOT (odds ratio (OR), 95% confidence interval (CI) = 1.37 (1.02, 1.84), p = 0.03); The incidence of TVT-O voiding difficulty was lower than that of TVT (OR, 95% CI = 2.94 (1.20, 7.20), p = 0.02); And the incidence of vaginal mucosal perforation of TOT was lower than that of TVT (OR, 95% CI = 0.11 (0.02, 0.61), p = 0.01). CONCLUSIONS: The four surgical procedures, TVT, TOT, TVT-O and TVT-S, were relatively similar in terms of SUI outcomes. TVT had a higher subjective cure rate than TOT and a higher incidence of postoperative dyspareunia and vaginal mucosal perforation.

Estimating cure and risk of death from other causes of cancer patients: EUROCARE-6 data on head & neck, colorectal, and breast cancers.

BACKGROUND: To estimate net survival and cancer cure fraction (CF), i.e. the proportion of patients no longer at risk of dying from cancer progression/relapse, a clear distinction needs to be made between mortality from cancer and from other causes. Conventionally, CF is estimated assuming no excess mortality compared to the general population. METHODS: A new modelling approach, that corrects for patients' extra risk of dying (RR) from causes other than the diagnosed cancer, was considered to estimate both indicators. We analysed EUROCARE-6 data on head and neck (H&N), colorectal, and breast cancer patients aged 40-79, diagnosed from 1998 to 2002 and followed-up to 31/12/2014, provided by 65 European cancer registries. FINDINGS: Young male H&N cancer patients have 4 times the risk of dying from other causes than their peers, this risk decreases with age to 1.6. Similar results were observed for female. We observed an absolute increase in CF of 30 % using the new model instead of the conventional one. For colorectal cancer, CF with the new model increased by a maximum of 3 % for older patients and the RR ranged from 1 to 1.2 for both sexes. CF of female breast cancer ranged from 73 % to 79 % using the new cure model, with RR between 1.2 and 1.4. INTERPRETATION: Not considering a RR> 1 leads to underestimate the proportion of patients not bound to die of their diagnosed cancer. Estimates of cancer mortality risk have an important impact on patients' quality of life.

Beyond Occam's Razor: Concurrent Non-functional Pituitary Macroadenoma and Metastatic Hepatocellular Carcinoma in a Patient With Functional Cure of Hepatitis B.

Occam's razor, the principle of parsimony, is frequently employed in medicine to derive a single diagnosis from a patient's myriad symptoms. Conversely, Hickam's dictum, which embraces the principle of plenitude by considering multiple diagnoses for a patient's presentation, is often underutilized or not as widely recognized as Occam's razor. The application of Hickam's dictum is particularly crucial when evaluating nonspecific symptoms such as fatigue, which can manifest in various diseases. This report describes the case of a 72-year-old man with a history of functional cure for hepatitis B who presented with chronic fatigue and hyponatremia. Initially, he was diagnosed with non-functional pituitary macroadenoma and panhypopituitarism. Two months following pituitary surgery, the onset of dyspepsia and the recurrence of fatigue revealed metastatic tumors in the liver, stomach, pancreas, left adrenal gland, and peri-pancreatic lymph nodes. A liver biopsy confirmed the diagnosis of hepatocellular carcinoma. This case highlights the importance of considering multiple, potentially co-existing conditions based on the patient's symptoms and risk factors to complete the thorough diagnoses. Additionally, it emphasizes the need to remain vigilant regarding the risk of liver cancer in patients with a history of chronic hepatitis B infection, irrespective of a functional cure.

Discovery of hepatitis B virus subviral particle biogenesis inhibitors from a bioactive compound library.

High levels of hepatitis B virus (HBV) surface antigen (HBsAg) in the blood of chronic HBV carriers are considered to drive the exhaustion of antigen-specific T and B lymphocytes and thus responsible for the persistence of infection. Accordingly, therapeutic elimination of HBsAg may facilitate the activation of adaptive antiviral immune responses against HBV and achieve a functional cure of chronic hepatitis B. We discovered recently that an amphipathic alpha helix spanning W156 to R169 of HBV small envelope (S) protein plays an essential role in the morphogenesis of subviral particles (SVPs) and metabolism of S protein. We thus hypothesized that pharmacological disruption of SVP morphogenesis may induce intracellular degradation of S protein and reduce HBsAg secretion. To identify inhibitors of SVP biogenesis, we screened 4417 bioactive compounds with a HepG2-derived cell line expressing HBV S protein and efficiently secreting small spherical SVPs. The screen identified 24 compounds that reduced intracellular SVPs and secreted HBsAg in a concentration-dependent manner. However, 18 of those compounds inhibited the secretion of HBsAg and HBeAg in HBV replicon transfected HepG2 cells at similar efficiency, suggesting each of those compounds may disrupt a common cellular function required for the synthesis and/or secretion of these viral proteins. Interestingly, lycorine more efficiently inhibited the secretion of HBsAg in HepG2 cells transfected with HBV replicons, HepG2.2.15 cells and HBV infected - HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). The structure activity relationship and antiviral mechanism of lycorine against HBV have been determined.

The efficacy and safety of inhaled antibiotics for pneumonia: A Systematic Review and Meta-Analysis.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of inhaled antibiotics for adults with pneumonia by meta-analysis. METHODS: Literature retrieval was completed through five databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) by the deadline of May 31, 2024. The process of study selection and data extraction were performed independently by two reviewers. The quality of observational studies and randomized controlled trial (RCT) studies were evaluated by Newcastle Ottawa scale and Jadad scale, respectively. The primary outcomes included mortality, clinical cure, and microbiological cure. Secondary outcomes were recurrence and renal impairment. RESULTS: There were 30 studies were analyzed, including 12 RCT studies and 18 observational studies. Inhaled antibiotics did not significantly reduce mortality in RCT studies (odds ratio (OR)=1.06, 95% confidence interval (CI): 0.80-1.41). Inhaled antibiotics were associated with higher rates of clinical cure (OR=1.47 95%CI: 0.82-2.66 in RCT studies and OR=2.09, 95%CI: 1.36-3.21 in observational studies) and microbiological cure (OR=7.00 in RCT studies and OR=2.20 in observational studies). Subgroup analysis showed patients received inhaled antibiotics combined with intravenous administration and inhaled amikacin had better improvements of mortality, clinical cure and microbiological cure. Inhaled antibiotics were not associated with recurrence. The pooled OR of renal impairment were 0.65 (95%CI: 0.27-1.13; I-squared=43.5%, P=0.124) and 0.63(95%CI: 0.26-1.11; I-squared=69.0%, P=0.110) in RCT studies and observational studies, respectively. CONCLUSIONS: Inhaled antibiotics decreased risk of renal impairment and achieved significant improvements of clinical and microbiological cure in patients with pneumoniae.

Relationship between the polymerization distance of monowave and polywave light-curing units and the irradiance and physical properties of dental resin-based composites.

PURPOSE: To evaluate the influence of the polymerization distance of monowave and polywave light curing units (LCUs) on the measured irradiance relative to the value reported by the manufacturer in relation to the physical properties of resin-based composites (RBCs). METHODS: Four LCUs were used: one monowave and three polywave. The irradiance was measured with a digital radiometer. Depth of cure (DC) and flexural strength (FS) tests were performed according to ISO 4049:2019 at polymerization distances of 0 mm and 5 mm. RESULTS: The irradiance of all LCUs was higher than that reported by the manufacturer (>25-64%). The irradiance of the four LCUs was reduced when polymerization was performed at between 0 to 5 mm (paired t-test, P < 0.001). The DC at 0 mm was similar in all groups but was significantly decreased at 5 mm distance (ANOVA P < 0.001). FS showed differences among the LCUs at 0 mm (ANOVA P < 0.001) and was affected by the polymerization distance. The elastic modulus was unaffected by the LCU used or the distance (ANOVA P > 0.001). CONCLUSIONS: The LCU must be positioned as near as possible to RBCs during the polymerization process, as increased distance negatively affects the depth of cure and flexural strength.

Activity for CUREs to increase student understanding and application of responsible authorship and publication practices.

Professional development of scientists is enhanced by training students in responsible conduct of research earlier in their careers. One aspect of responsible conduct of research is authorship ethics, which concerns granting of credit to those who make intellectual contributions to the research. The activity discussed in this article emphasizes how authorship ethics can be integrated with Course-based Undergraduate Research Experience (CURE) and includes an adaption that could also be used for independent research students. The activity allows students to reflect upon inequalities and problems seen in scientific authorship, including gender bias, failure to credit effort (ghostwriters), and inclusion of authors that did not meaningfully contribute to the work (honorary/gift authorship). Themes seen in student reflections on how they could demonstrate ethics in authorship included: determining authorship by contribution, appropriate attributions on curriculum vitas (CV) and posters, different credit levels, understanding authorship criteria, and tracking contributions. Themes seen in student reflections on the importance of authorship were proper authorship credit distribution, authorship impacting career opportunities, and accountability in research. In the activity, students also created attributions for a poster to be presented from their research. We found that most students were able to create attributions that were correctly formatted, included the same authors, and positioned authors in the same order as other group members, matching what was presented on the finalized poster. We found that students' reflection on authorship and this professionalization of their activities in their CURE led to modest increases in their view of themselves as scientists.

All GLP-1 Agonists Should, Theoretically, Cure Alzheimer's Dementia but Dulaglutide Might Be More Effective Than the Others.

Addressing the dysfunctions of all brain cell types in Alzheimer's disease (AD) should cure the dementia, an objective that might be achieved by GLP-1 agonist drugs, because receptors for GLP-1 are present in all of the main brain cell types, i.e., neurons, oligodendroglia, astroglia, microglia, endothelial cells and pericytes. This article describes the benefits provided to all of those brain cell types by GLP-1 agonist drugs. The article uses studies in humans, not rodents, to describe the effect of GLP-1 agonists upon cognition, because rodents' brains differ from those of humans in so many ways that results from rodent studies may not be totally transferable to humans. Commercially available GLP-1 agonists have mostly shown either positive effects upon cognition or no effects. One important reason for no effects is a reduced rate of entering brain parenchyma. Dulaglutide has the greatest entry to brain, at 61.8%, among the available GLP-1 agonists, and seems to offer the best likelihood for cure of AD. Although there is only one study of cognition that used dulaglutide, it was randomized, placebo controlled, and very large; it involved 8828 participants and showed significant benefit to cognition. A clinical trial to test the hypothesis that dulaglutide may cure AD should have, as its primary outcome, a 30% greater cure rate of AD by dulaglutide than that achieved by an equipoise arm of, e.g., lithium plus memantine.

[New progress on the clinical study of antiviral therapy for chronic hepatitis B in children].

Diagnosis and treatment of hepatitis B virus (HBV) infection in children is a hotspot of concern in the field of HBV infection. This article reviews the current status and progress of antiviral treatment for children with chronic hepatitis B (CHB) in recent years, focusing on clinical issues such as the choice of antiviral treatment regimen for children with HBeAg-positive CHB (immune-clearance phase), the necessity of antiviral treatment for children with HBeAg-positive HBV infection (immune-tolerance phase), and the timing of antiviral treatment for infants with HBV infection, to explore the relevant factors that may affect the clinical cure of children with CHB. At the same time, based on the expert consensus on the prevention and treatment of children with CHB just published by Chinese experts, relevant diagnosis and treatment plans are proposed, with a view to providing reference and basis for clinical decision-making in children with CHB.

[Therapeutic strategies, practice, and prospect of a clinical cure for chronic hepatitis B in China].

Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.

Distinct TB-antigen stimulated cytokine profiles as predictive biomarkers for unfavorable treatment outcomes in pulmonary tuberculosis.

Introduction: The assessment of tuberculosis (TB) treatment outcomes predominantly relies on sputum culture conversion status. To enhance treatment management, it is crucial to identify non-sputum-based biomarkers that can predict unfavorable outcomes. Cytokines are widely studied as diagnostic biomarkers for active TB. However, their potential as indicators for unfavorable treatment outcomes remains uncertain. Methodology: This study was conducted within a well-characterized cohort comprising newly diagnosed patients with drug-sensitive pulmonary TB, confirmed through sputum smear and culture positivity. Our objective was to elucidate the TB antigen-stimulated cytokine profile at pre-treatment and at 2 months into anti-TB treatment (ATT) in patients with unfavorable treatment outcomes (cases, n = 27) in comparison to recurrence-free, microbiologically cured controls (n = 31). Whole blood was stimulated with TB antigens using the QuantiFERON In-tube gold method, and plasma supernatants were subjected to a panel of 14 cytokine measurements. Results: In our study, pre-treatment analysis revealed that eight cytokines (IL-2, IFN-γ, TNF-α, IL-6, IL-10, IL-17A, IL-18, and GM-CSF) were significantly elevated at baseline in cases compared to cured controls, both in unstimulated conditions and following TB antigen (CFP10, ESAT6, and TB7.7) stimulation. A similar pattern was observed at the 2-month mark of ATT, with eight cytokines (IL-2, IL-10, IL-13, IFN-γ, IL-6, IL-12p70, IL-17A, and TNF-α) showing significant differences between the groups. Importantly, no variations were detected following mitogen stimulation, underscoring that these distinctive immune responses are primarily driven by TB-specific antigens. Conclusion: Our findings indicate that individuals with unfavorable TB treatment outcomes display a characteristic cytokine profile distinct from TB-cured patients, even before commencing ATT. Therefore, the levels of specific cytokine pre-treatment and at the 2-month point in the course of treatment may serve as predictive immune markers for identifying individuals at risk of unfavorable TB treatment outcomes, with these responses being predominantly influenced by TB-specific antigens.

Degree of Cure, Microstructures, and Properties of Carbon/Epoxy Composites Processed via Frontal Polymerization.

The frontal polymerization (FP) of carbon/epoxy (C/Ep) composites is investigated, considering FP as a viable route for the additive manufacturing (AM) of thermoset composites. Neat epoxy (Ep) resin-, short carbon fiber (SCF)-, and continuous carbon fiber (CCF)-reinforced composites are considered in this study. The evolution of the exothermic reaction temperature, polymerization frontal velocity, degree of cure, microstructures, effects of fiber concentration, fracture surface, and thermal and mechanical properties are investigated. The results show that exothermic reaction temperatures range between 110 °C and 153 °C, while the initial excitation temperatures range from 150 °C to 270 °C. It is observed that a higher fiber content increases cure time and decreases average frontal velocity, particularly in low SCF concentrations. This occurs because resin content, which predominantly drives the exothermic reaction, decreases with increased fiber content. The FP velocities of neat Ep resin- and SCF-reinforced composites are seen to be 0.58 and 0.50 mm/s, respectively. The maximum FP velocity (0.64 mm/s) is observed in CCF/Ep composites. The degree of cure (αc) is observed to be in the range of 70% to 85% in FP-processed composites. Such a range of αc is significantly low in comparison to traditional composites processed through a long cure cycle. The glass transition temperature (Tg) of neat epoxy resin is seen to be approximately 154 °C, and it reduces slightly to a lower value (149 °C) for SCF-reinforced composites. The microstructures show significantly high void contents (12%) and large internal cracks. These internal cracks are initiated due to high thermal residual stress developed during curing for non-uniform temperature distribution. The tensile properties of FP-cured samples are seen to be inferior in comparison to autoclave-processed neat epoxy. This occurs mostly due to the presence of large void contents, internal cracks, and a poor degree of cure. Finally, a highly efficient and controlled FP method is desirable to achieve a defect-free microstructure with improved mechanical and thermal properties.

A Numerical Model to Predict the Relaxation Phenomena in Thermoset Polymers and Their Effects on Residual Stress during Curing, Part II: Numerical Evaluation of Residual Stress.

This article proposes a numerical routine to predict the residual stresses developing in an epoxy component during its curing. The scaling of viscoelastic properties with the temperature and the degree of conversion is modeled, adopting a mathematical formulation that considers the concurrent effects of curing and structural relaxation on the epoxy's viscoelastic relaxation time. The procedure comprises two moduli: at first, the thermal-kinetical problem is solved using the thermal module of Ansys and a homemade routine written in APDL, then the results in terms of temperature and the degree of conversion profiles are used to evaluate the viscoelastic functions, and the structural problem is solved in the mechanical module of Ansys, allowing the residual stresses calculation. The results show that the residual stresses mainly arise during cooling and scale with the logarithm of the Biot number.

Tumor desmoplasia outperforms preoperative serum calcitonin as surgical biomarker in sporadic medullary thyroid cancer.

BACKGROUND: Conceptually, thyroid tumor desmoplasia may be better suited for excluding node metastases in sporadic MTC than preoperative serum calcitonin levels. METHODS: This analysis included 181 patients with unilateral sporadic MTC graded on the 7-grade desmoplasia scale after thyroidectomy and neck dissection. RESULTS: When thyroid tumor desmoplasia reached 1% and ≥50%, node metastases increased from 0% to 7% (median of 0 metastases) and 83% (median of 7.5 metastases), microscopic lymphatic invasion from 0% to 3% and 35%, extrathyroid extension from 0% to 5% and 22%, and extranodal growth from 0% to 0% and 44%, whereas biochemical cure declined from 100% to 95% and 25%. Thyroid tumor diameters and basal calcitonin overlapped widely among the seven desmoplasia groups, precluding differentiation by thyroid tumor size or serum calcitonin levels. CONCLUSIONS: Thyroid tumor desmoplasia, unlike serum calcitonin levels, discriminates extremely well between node-negative and node-positive sporadic MTC, opening new avenues for precision surgery.

Influence of the hydroperoxide structure on the reactivity and mechanical properties of self-cure dental composites.

OBJECTIVES: Hydroperoxides are key constituents of two-component dental materials. The objective of this study was to evaluate the influence of the hydroperoxide structure on the reactivity and on the mechanical properties of self-cure composites. METHODS: Hydroperoxides HP1-3 were synthesized by selective catalytic oxidation of the corresponding para-substituted cumene precursors and isolated in high purity. They were characterized by 1H NMR and 13C NMR spectroscopy. 16 self-cure composites, based on the redox initiator system hydroperoxide (Cumene hydroperoxide (CHP), HP1-3 or tert.-Amyl hydroperoxide (TAH))/polymerizable thiourea ATU1/copper(II) acetylacetonate, were formulated in Sulzer Mixpac two-component syringes. An equimolar hydroperoxide/ATU1 ratio was selected for each self-cure composite. The reactivity and the final double-bond conversions obtained with these two-component materials was assessed using RT-FTIR spectroscopy. The flexural strength and modulus were measured using a three-point bending setup, after storage of the specimens for 45 min at 37 °C (dry) and for 24 h in water at 37 °C. The working time of each self-cure composite was measured using an oscillating rheometer. RESULTS: CHP derivatives bearing an electron withdrawing group (HP2: ester or HP3: nitrile) in the para position were found to be more reactive than CHP, whereas the compound bearing an electron donating group (tert-butyl, HP1) was less reactive; molecular modelling data were reported for a better understanding of this structure/reactivity/efficiency relationship. All CHP derivatives were more reactive than the aliphatic hydroperoxide TAH. Excellent mechanical properties were obtained with self-cure composites containing either CHP or a para-functionalized CHP derivative. By carefully selecting the amounts of oxidizing/reducing agents and metal catalyst, suitable working times can be obtained with all evaluated hydroperoxides. HP3, thanks to its high reactivity, is nonetheless the most promising compound. SIGNIFICANCE: The curing rate of self-cure composites can be adapted by modifying the structure of the hydroperoxide. In agreement with molecular modelling data, the incorporation of CHP derivatives bearing an electron withdrawing group in the para position is particularly attractive. Indeed, due to a significant reactivity enhancement, the desired properties (working time, flexural strength/modulus) can be obtained by incorporating moderate amounts of hydroperoxide/acylthiourea as well as particularly low contents of metal catalyst to the two-component dental materials.

Effect of Dietary Simulating Solvents on the CAD-CAM Provisional Restorative Materials' Microhardness and Color Stability Properties: An in vitro Study.

Purpose: This in vitro study investigated the effects of dietary solvents on the microhardness and color stability of CAD/CAM provisional restorations compared to conventional materials. Methods: Disc-shaped specimens (n=200) were fabricated from self-cured acrylic resin, two 3D-printing resins (FormLabs, NextDent), and a milled material (TelioCAD). Randomization assigned specimens (n=10/group) to immersion solutions: artificial saliva, citric acid, heptane, coffee, and tea. Microhardness and color stability were evaluated. One-way and three-way ANOVA with Tukey's post hoc test analyzed the data. Results: Dietary solvents significantly reduced the surface microhardness of all tested materials (p<0.05). Unpolished surfaces exhibited greater color changes compared to polished ones (p<0.05) across all materials. Coffee and tea induced the most substantial reductions in hardness and the most significant color alterations (p<0.05), whereas saliva and citric acid had minimal effects. Conclusion: Milled provisional restorations exhibited superior hardness and color stability. Dietary solvents significantly affected material properties over time, highlighting the importance of material selection for clinical applications.