Dietary omega-3 fatty acids modulate the production of platelet-derived microvesicles in an in vivo inflammatory arthritis model.

PURPOSE: The aim of this study was to investigate the effects of different ω-3 polyunsaturated fatty acid (PUFA) enriched diets, including a novel renewable plant source of ω-3 fatty acids (Buglossoides arvensis), on the development and progression of rheumatoid arthritis (RA). METHODS: RA was induced in mice consuming experimental diets using the K/BxN model. The experimental diets consisted of either a western control diet (control), diets containing B. arvensis oil or fish oil. The effects of the diets on platelets, platelet microvesicles (PMVs), and inflammatory markers such as clinical index, ankle thickness and cytokine/chemokine release were measured. RESULTS: While ω-3 PUFA-enriched diets did not prevent the development of arthritis in the K/BxN model, a significant decrease in ankle swelling was observed compared to the control group. Platelets isolated from mice consuming either low content of B. arvensis oil or fish oil diets exhibited significantly decreased PMVs production compared to mice consuming the control diet. CONCLUSION: Our study provides insight into the contribution of ω-3 PUFA supplementation in modulating the pro-inflammatory phenotype of platelets in RA pathology. Furthermore, our study suggests that low concentrations of dietary B. arvensis oil may have similar anti-inflammatory potential seen with dietary fish oil supplementation.

Effect of preparation design on fracture strength of compromised molars restored with direct composite resin restorations: An in vitro and finite element analysis study.

STATEMENT OF PROBLEM: More data are needed on the influence of preparation design on the fracture strength, failure type, repairability, and polymerization-induced cracks of molar teeth restored with direct composite resin restorations. PURPOSE: This in vitro and finite element analysis study investigated the effect of different preparation designs on fracture strength, failure type, repairability, tooth deformation, and the formation of polymerization-induced cracks of compromised molars restored with direct composite resin restorations. MATERIAL AND METHODS: Human molars (n=64) were randomly assigned to 4 different preparation designs: undermined inlay (UI), extended inlay (EI), restricted overlay (RO), and extended overlay (EO). The teeth were restored using direct composite resin and subjected to artificial thermomechanical aging in a mastication simulator, followed by load-to-failure testing. Three-dimensional (3D) finite element analysis was conducted to assess tooth deformation. Polymerization-induced cracks were evaluated using optical microscopy and transillumination. The fracture strength data were analyzed using a Kruskal-Wallis test, while the failure mode, repairability, and polymerization cracks were analyzed using the Fisher exact test (α=.05). RESULTS: All specimens withstood thermomechanical aging, and no statistically significant difference in fracture strength was observed among the 4 preparation designs (P>.05). The finite element analysis showed differences in tooth deformation, but no correlation was observed with in vitro fracture resistance. The RO and EO groups presented significantly more destructive failures compared with the UI and EI groups (P<.01). The RO group had significantly fewer repairable failures than the UI and EI groups (P=.024). A correlation was found between higher frequencies of repairability and higher tooth deformation. A significant correlation between the increase in microfractures and preparation design was observed (P<.01), with the UI group exhibiting a higher increase in microfracture size compared with the EO group (P<.05). CONCLUSIONS: No influence of preparation design on the fracture strength of compromised molars restored with direct composite resin restorations was evident in this study, but the failure mode of cusp coverage restorations was more destructive and often less repairable. The finite element analysis showed more tooth deformation in inlay preparations, with lower stresses within the root, leading to more reparable fractures. Since cusp coverage direct composite resin restorations fractured in a more destructive manner, this study suggests that even a tooth with undermined cusps should be restored without cusp coverage.

Partial glass-ceramic posterior restorations with margins beyond or above the cemento-enamel junction: An observational retrospective clinical study.

PURPOSE: This observational retrospective clinical study aimed to investigate the survival and success rates of partial indirect lithium disilicate restorations with margins extending above or beyond the cementoenamel junction (CEJ). METHODS: The study included patients who underwent partial indirect lithium disilicate restorations with immediate dentin sealing (IDS) between January 2008 and October 2018. All the restorations were placed in a single general dental practice following a standardized protocol. The impact of various predictive variables on the survival rates was assessed. Moreover, modified United States Public Health Service (USPHS) criteria were used to evaluate the survival quality. RESULTS: Totally 1146 partial indirect lithium disilicate restorations in 260 patients were evaluated over an average period of 7.5 years. The cumulative survival and success rates were 97.3% and 95.3%, respectively. Margins extending beyond the cemento-enamel junction did not increase the risk of success or survival failure (P > 0.05). Patients with a high risk of caries, male sex, or non-vital teeth had a significantly higher risk of restoration failure (P < 0.05). Restorations with longer clinical service times exhibited marginally lower clinical quality (P < 0.001). CONCLUSIONS: Partial indirect glass-ceramic restorations demonstrated survival and success rates of 97.3% and 95.3%, respectively, over an extended period. However, a higher risk of restoration failure existed in patients with a high caries risk for (pre)molars that had undergone endodontic treatment and in males. In terms of the risk of success or survival failure, comparable results were obtained for the positions of the restoration margin in relation to the cemento-enamel junction.

Effects of androgen deprivation therapy on elderly men with high-risk prostate cancer: PROSARC observational study.

INTRODUCTION: Prostatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient's quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation. We present data from an interim analysis. MATERIALS AND METHODS: PROSARC is a national (Spain) prospective observational study (May-2022-May-2025) still in progress in 2 hospitals. It includes patients with high-risk PC, aged ≥70 years, non-candidates for local treatment and scheduled to start androgen deprivation therapy. The following variables are analyzed: comorbidity, frailty (Fried frailty phenotype criteria), osteoporosis, sarcopenia (EWGSOP2), fat mass and muscle mass, before treatment and after 6 months of follow-up. RESULTS: A 6-month follow-up was completed by 12/25 included patients (mean age, 84 years), with a high baseline prevalence of pre-frailty/frailty (67.7%), sarcopenia (66.7%) and osteoporosis (25%). Treatment did not significantly alter these variables or comorbidity. We observed changes in body mass index (p=0.666), decreased mean value of appendicular muscle mass (p=0.01) and increased percentage of fat mass (p=0.012). CONCLUSION: In patients with high-risk PC, advanced age and a considerable prevalence of osteoporosis, frailty and sarcopenia, androgen deprivation (ADT; 6 months) produces decreased muscle mass without impact on the incidence of the known adverse effects of androgen deprivation.

Biomechanical behavior of molars restored with direct and indirect restorations in combination with deep margin elevation.

STATEMENT OF PROBLEM: The existing knowledge is insufficient for comprehending the fatigue survival and fracture resistance of molars that have deep approximal direct and indirect restorations, whether with or without deep margin elevation (DME). PURPOSE: The aim of this laboratory and in silico study is to investigate the fatigue survival, fracture strength, failure pattern and tooth deformation of molars restored with DME in combination with a direct or indirect restoration. MATERIAL AND METHODS: This study utilized 45 extracted sound human molars, divided into three groups (n = 15). Standardized 100% inter-cuspal inlay preparations were performed, extending 2 mm below the CEJ and immediate dentin sealing (IDS) was applied. Group 1 (Co_1) was restored with direct composite; Group 2 (Hyb_2) with a 2 mm DME of direct composite and a glass-ceramic lithium disilicate restoration; Group 3 (Cer_3) a glass-ceramic lithium disilicate restoration. All specimens were exposed to a fatigue process involving thermal-cyclic loading (50N for 1.2 × 106 cycles at 1.7 Hz, between 5 and 55 °C), if teeth survived, they were fractured using a load-to-failure test and failure types were analyzed. Finite element analysis (FEA) was conducted to assess tooth deformation and tensile stress in the restorations. Statistical evaluation of fracture strength was conducted using the Kruskal-Wallis test. Fisher's exact test was utilized to analyze the fracture types and repairability. A statistical significance level of α < 0.05 was set for all analyses. RESULTS: All specimens successfully withstood the fatigue testing procedure, and no statistically significant differences in fracture strength were observed among the three groups (P > 0.05). The Fisher's exact test indicated a significant association between the restorative material and fracture type (F2 = 18.315, df = 2, P = 0.004), but also for repairability (F2 = 13.725, df = 2, P = 0.001). Crown-root fractures were significantly more common in the Cer_3 group compared to the Co_1 group (P = 0.001) and the Co_1 group had significantly more repairable fractures (F2 = 13.197, df = 2, P = 0.001). FEA revealed comparable outcomes of deformation among models and higher maximum tensile stress on models with higher frequency of catastrophic failures. CONCLUSIONS: All tested restoration materials exhibited comparable fatigue survival and fracture strength in this laboratory and in silico study. However, it is important to recognize the potential for more severe and irreparable fractures when opting for deeply luted glass-ceramic inlay restorations in clinical practice. In such cases, it would be prudent to consider the alternative option being a direct composite approach, because of its more forgiving fracture types and repairability. CLINICAL IMPLICATIONS: Molars with deep approximal direct and indirect restorations, whether with or without DME, are comparable in their fatigue survival and fracture resistance to withstand intra-oral forces. Deep direct restorations exhibit more repairable fractures compared to deeply luted glass-ceramics.

Side group dependent room temperature crystallization-induced phosphorescence of benzil based all organic phosphors.

In this work, we report alkoxy substituted benzil based all organic room temperature phosphors which showed crystallization induced phosphorescence (CIP). Nine title compounds were prepared with various alkyl lengths (OCnH2n+1: n = 8-16) and the effect of alkyl side group length on the phosphorescence performance was investigated, as compared to p-anisil. It was found that both phosphorescence quantum yield and lifetime increased concomitantly as the alkyl length increased up to nonyloxy (BZL-OC9). Further increase in the carbon number caused the phosphorescence performance to deteriorate due to greater conformational freedom of the side groups. An incredible quantum yield of 70% was achieved for BZL-OC9. A promising finding is that the increased quantum yield was accompanied by the increase in the lifetime relative to p-anisil, which has been historically challenging. Single crystallography coupled with UV-Vis spectroscopy revealed that a higher level of intermolecular π-π interactions was observed from p-anisil while more alkyl interactions with less intermolecular π-orbital overlap were found for BZL-OC8. As a result, molecular rigidification with less phosphorescence quenching was achieved for BZL-OC8 leading to enhanced performance. A precipitation study on a dichloromethane solution as a function of the content of MeOH (poor solvent) proved that the emission of the BZL-OCn system is truly aggregation-induced. The current work demonstrates that strategic side group engineering could be a promising approach to developing high-performance all organic phosphors as well as improving the properties of existing phosphors.

Systematics and spatio-temporal evolutionary patterns of the flavopilosa group of Drosophila (Diptera, Drosophilidae).

The Drosophila flavopilosa group comprises morphologically cryptic species that are ecologically restricted to feeding, breeding and ovipositing on flowers of Cestrum and Sessea (Solanaceae). Previous studies confirmed the monophyly of the group and the success of DNA barcoding in identifying a subset of its species, but several others remain yet to be evaluated. Furthemore, the taxonomy of the group remains incomplete, with only nine of the 17 species assigned to subgroups. Here, we accessed the phylogenetic relationships and spatio-temporal evolutionary patterns of the flavopilosa group based on a mitochondrial and two nuclear genes, providing the first molecular support to the subdivision of the group and suggesting a new taxonomic scheme for its species. Barcoding proved to be an effective tool, as all species were reciprocally monophyletic and different analyses of species delimitation yielded congruent results. The close relationship of D. flavopilosa with D. cestri and D. cordeiroi was strongly supported, suggesting that the latter should be placed in the flavopilosa subgroup together with the first. Furthermore, D. mariaehelenae was positioned as sister to D. incompta, supporting its inclusion in the nesiota subgroup. Despite new taxonomic assignments, the synapomorphic status of the diagnostic characters proposed for both subgroups was supported. Based on them, each of the remaining species were placed into one of both subgroups. Divergence time estimates suggest that their diversification coincided with the divergence of Sessea and Cestrum, providing an interesting case of coevolution.

Clinical performance of bonded partial lithium disilicate restorations: The influence of preparation characteristics on survival and success.

OBJECTIVES: The aim of this study was to investigate the influence of preparation characteristics on the survival, success, and clinical performance of partial indirect lithium disilicate restorations with immediate dentin sealing. METHODS: This retrospective clinical study evaluated partial indirect lithium disilicate restorations placed in conjunction with Immediate Dentin Sealing (IDS) in (pre)molar teeth between March 2018 and May 2021. The restorations were luted using pre-heated composite. The study focused on survival, success, and clinical performance, which was evaluated using the modified United States Public Health Service (USPHS) criteria. Results were analyzed using the Kaplan-Meier estimates, log-rank tests, and Fisher exact tests. RESULTS: Partial indirect lithium disilicate restorations (N = 454) were evaluated in 214 patients. The mean evaluation time was 37 months, with a cumulative survival rate of 99.2 % and a cumulative success rate of 97.6 %. Fourteen failures occurred, with endodontic pathology as the predominant failure mode, followed by secondary caries, debonding, and tooth fracture. No statistically significant influence of the preparation variables on survival and success was observed (p > .05). The short-term clinical performance was clinically acceptable in > 90 % of the evaluations. CONCLUSIONS: This retrospective study on partial indirect lithium disilicate restorations in conjunction with IDS demonstrates survival and success rates of 99.2 and 96.7 % over a mean evaluation period of 37 months. A marked influence of the studied preparation characteristics on the survival, success and clinical performance of lithium disilicate partial restorations could not be demonstrated. Partial lithium disilicate restorations exhibit good clinical performance in >90 % of the cases. CLINICAL SIGNIFICANCE: The results of this study suggest that preparation characteristics had no significant impact on the survival, success, and clinical performance of partial lithium disilicate restorations in conjunction with IDS. Results show good clinical performance and high survival and success rates, regardless of preparation characteristics.

Establishing clinically meaningful ranges of metal hypersensitivity in orthopaedic patients using COVID-19 vaccine-induced adaptive immune responses from fully vaccinated adults.

Background: This study aimed to assess metal sensitization ranges among orthopaedic patients by comparing adaptive immune responses in all-comer pre- and post-operative orthopaedic adults who were COVID-19 unvaccinated or vaccinated vs patients with a painful aseptic implant by lymphocyte transformation test (LTT) to SARS-CoV-2-Spike-Protein (SP) and implant metal(s), respectively. Methods: Data were retrospectively reviewed from three independent groups: unvaccinated COVID-19 adults (n = 23); fully COVID-19 vaccinated adults (n = 35); unvaccinated, painful aseptic implant patients with history of metal allergy (n = 98). Standard in vitro LTT for SP and implant metal(s) (nickel, cobalt) were performed and rated as negative (stimulation index [SI]<2), mild (SI ≥ 2), positive (SI ≥ 4-15), and high sensitization (SI > 15) adaptive immune responses to tested antigen. Results: Overall, 17/23 (74%) of unvaccinated adults showed negative to mild LTT ranges, and 35/35 (100%) of vaccinated showed mild to positive LTT ranges to SP. Vaccinated individuals showed significantly higher median SI (16.1) to SP than unvaccinated (median SI, 1.7; P < 0.0001). Most vaccinated adults (94%) showed a lymphocyte SI > 4 to SP, establishing LTT SI ≥ 4 with >90% sensitivity for diagnosing effective COVID-19 adaptive immune responses. Significantly fewer painful orthopaedic patients (41%) showed comparable elevated levels of lymphocyte metal sensitivity at SI ≥ 4 compared to vaccinated group (P < 0.0001). Conclusions: Vaccinated adults showed significantly higher lymphocyte SI to SP than unvaccinated indicating that SI ranges ≥4 should be set as unequivocally diagnostic of LTT-positive adaptive immune responses to tested antigen. This analysis supports using higher LTT SI ranges (SI ≥ 4) in diagnosing clinical orthopaedic-related Type IV metal-hypersensitivity responses among orthopaedic patients.

Effect of Propofol on Heart Rate and Its Coupling to Cortical Slow Waves in Humans.

BACKGROUND: Propofol causes significant cardiovascular depression and a slowing of neurophysiological activity. However, literature on its effect on the heart rate remains mixed, and it is not known whether cortical slow waves are related to cardiac activity in propofol anesthesia. METHODS: The authors performed a secondary analysis of electrocardiographic and electroencephalographic data collected as part of a previously published study where n = 16 healthy volunteers underwent a slow infusion of propofol up to an estimated effect-site concentration of 4 µg/ml. Heart rate, heart rate variability, and individual slow electroencephalographic waves were extracted for each subject. Timing between slow-wave start and the preceding R-wave was tested against a uniform random surrogate. Heart rate data were further examined as a post hoc analysis in n = 96 members of an American Society of Anesthesiologists Physical Status II/III older clinical population collected as part of the AlphaMax trial. RESULTS: The slow propofol infusion increased the heart rate in a dose-dependent manner (mean ± SD, increase of +4.2 ± 1.5 beats/min/[µg ml-1]; P < 0.001). The effect was smaller but still significant in the older clinical population. In healthy volunteers, propofol decreased the electrocardiogram R-wave amplitude (median [25th to 75th percentile], decrease of -83 [-245 to -28] µV; P < 0.001). Heart rate variability showed a loss of high-frequency parasympathetic activity. Individual cortical slow waves were coupled to the heartbeat. Heartbeat incidence peaked about 450 ms before slow-wave onset, and mean slow-wave frequency correlated with mean heart rate. CONCLUSIONS: The authors observed a robust increase in heart rate with increasing propofol concentrations in healthy volunteers and patients. This was likely due to decreased parasympathetic cardioinhibition. Similar to non-rapid eye movement sleep, cortical slow waves are coupled to the cardiac rhythm, perhaps due to a common brainstem generator.

Enhancing the Extinction Efficiency and Plasmonic Response of Bimetallic Nanoparticles of Au-Ag in Robust Thin Film Sensing Platforms.

The extinction efficiency of noble metal nanoparticles (NPs), namely gold (Au) and silver (Ag), are dependent on their size and surrounding dielectric. Exploiting the Localized Surface Plasmon Resonance (LSPR) phenomenon, the composition and structure of the NPs might be tailored to achieve a configuration that optimizes their response (sensitivity) to environmental changes. This can be done by preparing a bimetallic system, benefiting from the chemical stability of Au NPs and the higher scattering efficiency of Ag NPs. To enhance the LSPR sensing robustness, incorporating solid supports in the form of nanocomposite thin films is a suitable alternative. In this context, the NPs composed of gold (Au), silver (Ag), and their mixture in bimetallic Au-Ag NPs, were grown in a titanium dioxide (TiO2) matrix using reactive DC magnetron sputtering. Thermal treatment at different temperatures (up to 700 °C) tuned the LSPR response of the films and, consequently, their sensitivity. Notably, the bimetallic film with Au/Ag atomic ratio 1 exhibited the highest refractive index sensitivity (RIS), with a value of 181 nm/RIU, almost one order of magnitude higher than monometallic Au-TiO2. The nanostructural analysis revealed a wide NP size distribution of bimetallic NPs with an average size of 31 nm, covering about 20% of the overall surface area. These findings underscore the significant potential of bimetallic film systems, namely AuAg-TiO2, in LSPR sensing enhancement.

Tuning the Refractive Index Sensitivity of LSPR Transducers Based on Nanocomposite Thin Films Composed of Noble Metal Nanoparticles Dispersed in TiO2.

This work reports on the development of nanoplasmonic thin films consisting of Au, Ag, or Au-Ag nanoparticles dispersed in a TiO2 matrix and the optimization of the deposition parameters to tune their optical response. The thin films were produced by reactive DC magnetron sputtering of a Ti target with Au and/or Ag pellets placed on the erosion zone. The thicknesses (50 and 100 nm) of the films, the current density (75 and 100 A/m2) applied to the target (titanium), and the number of pellets placed on its surface were the deposition conditions that were used to tailor the optical (LSPR) response. The total noble metal content varied between 13 and 28 at.% for Au/TiO2 films, between 22 and 30 at.% for Ag/TiO2 films, and 8 to 29 at% for the Au-Ag/TiO2 systems with 1:1, 1:1.5, and 1:2 Au:Ag atomic ratios. After thermal annealing at 400 and 600 °C, LSPR bands were found for all films concerning the Au-TiO2 and Au-Ag/TiO2, while for Ag/TiO2, only for thin films with 28 and 30 at.% of Ag concentration. Refractive index sensitivity (RIS) was evaluated for Au and Au-Ag/TiO2 thin films. It was found that for bimetallic nanoparticles, the sensitivity can increase up to five times when compared to a monometallic nanoplasmonic system. Using Au-Ag/TiO2 thin films can decrease the cost of fabrication of LSPR transducers while improving their sensitivity.

Ten quick tips for fuzzy logic modeling of biomedical systems.

Fuzzy logic is useful tool to describe and represent biological or medical scenarios, where often states and outcomes are not only completely true or completely false, but rather partially true or partially false. Despite its usefulness and spread, fuzzy logic modeling might easily be done in the wrong way, especially by beginners and unexperienced researchers, who might overlook some important aspects or might make common mistakes. Malpractices and pitfalls, in turn, can lead to wrong or overoptimistic, inflated results, with negative consequences to the biomedical research community trying to comprehend a particular phenomenon, or even to patients suffering from the investigated disease. To avoid common mistakes, we present here a list of quick tips for fuzzy logic modeling any biomedical scenario: some guidelines which should be taken into account by any fuzzy logic practitioner, including experts. We believe our best practices can have a strong impact in the scientific community, allowing researchers who follow them to obtain better, more reliable results and outcomes in biomedical contexts.

Effect of preparation design on fracture strength of compromised molars restored with lithium disilicate inlay and overlay restorations: An in vitro and in silico study.

PURPOSE: The objective of this study was to determine the influence of different preparation designs on the fracture strength, failure type, repairability, formation of polymerization-induced cracks, and tooth deformation of structurally compromised molars restored with lithium disilicate inlays and overlays in combination with Immediate Dentin Sealing (IDS). MATERIAL AND METHODS: Human molars (N = 64) were randomly assigned to four different preparation designs: Undermined Inlay (UI), Extended Inlay (EI), Restricted Overlay (RO), and Extended Overlay (EO). The teeth were restored using lithium disilicate partial restorations and subjected to thermomechanical fatigue in a chewing simulator (1,2 × 10 (Mondelli et al., 2007) cycles on 50 N, 8000x 5-55 °C), followed by load to failure testing. In silico finite element analysis was conducted to assess tooth deformation. Polymerization-induced cracks were evaluated using optical microscopy and transillumination. Fracture strengths were statistically analyzed using a Kruskal-Wallis test, while the failure mode, repairability, and polymerization cracks were analyzed using Fisher exact test. RESULTS: The propagation of polymerization-induced cracks did not significantly differ among preparation designs. All specimens withstood chewing simulator fatigue, with no visible cracks in teeth or restorations. Fracture strength was significantly influenced by preparation design, with restricted overlay (RO) showing higher fracture strength compared to extended inlay (EI) (p = .042). Tooth deformation and fracture resistance correlated between in vitro and in silico analyses). UI exhibited a statistically less destructive failure pattern than EO (p < .01) and RO (p = .036). No statistically significant influence of the preparation design on repairability was observed. Groups with higher repairability rates experienced increased tooth deformation, leading to less catastrophic failures. CONCLUSIONS: The preparation design affected the fracture strength of compromised molars restored with lithium disilicate inlays and overlays, with significantly lower fracture strength for an extended inlay. The failure pattern of lithium disilicate overlays is significantly more destructive than that of undermined and extended inlays. The finite element analysis showed more tooth deformation in the inlay restorations, with lower forces in the roots, leading to less destructive fractures. Since cusp coverage restorations fracture in a more destructive manner, this study suggests the undermined inlay preparation design as a viable option for restoring weakened cusps.

A 32-month evaluation of lithium disilicate cantilever resin-bonded fixed dental prostheses to replace a missing maxillary incisor.

STATEMENT OF PROBLEM: The absence of a tooth in the esthetic zone can cause emotional and social distress. The use of minimally invasive and visually pleasing lithium disilicate resin-bonded fixed dental prostheses (RBFDPs) may be a suitable option for replacing a missing maxillary incisor. However, the available literature on lithium disilicate cantilever RBFDPs is limited. PURPOSE: This retrospective multicenter study assessed the survival and success rates of lithium disilicate anterior cantilever RBFDPs with an average follow-up period of 3 years up to 9 years. MATERIAL AND METHODS: RBFDPs delivered by 3 operators were clinically assessed for survival using a modified United States Public Health Service criteria list. The incidence density was determined for each criterion and operator. The standard error and 95% confidence interval were calculated for each incidence density difference (α=.05 for all analyses). RESULTS: A total of 108 RBFDPs were evaluated after a mean period of 32.45 months, ranging from 14 days to 111 months. None of the restorations exhibited failure, carious lesions, or fractures during the follow-up period. The primary reasons for reduced success rates were inflammation of the surrounding soft tissues and discoloration, with incidence densities of 0.074 and 0.057 per year, respectively. Significant differences were observed among RBFDPs from different operators for criteria that included adaptation, color match, marginal adaptation, polishability, surface staining, gingival health, and antagonist wear. CONCLUSIONS: Cantilever lithium disilicate RBFDPs appear to be suitable for short-term restoration. RBFDPs exhibited visible changes after short-term follow-up. However, these changes did not result in failure.

Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance.

Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27- and CD27+ T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations.

Conformational coupling of redox-driven Na+-translocation in Vibrio cholerae NADH:quinone oxidoreductase.

In the respiratory chain, NADH oxidation is coupled to ion translocation across the membrane to build up an electrochemical gradient. In the human pathogen Vibrio cholerae, the sodium-pumping NADH:quinone oxidoreductase (Na+-NQR) generates a sodium gradient by a so far unknown mechanism. Here we show that ion pumping in Na+-NQR is driven by large conformational changes coupling electron transfer to ion translocation. We have determined a series of cryo-EM and X-ray structures of the Na+-NQR that represent snapshots of the catalytic cycle. The six subunits NqrA, B, C, D, E, and F of Na+-NQR harbor a unique set of cofactors that shuttle the electrons from NADH twice across the membrane to quinone. The redox state of a unique intramembranous [2Fe-2S] cluster orchestrates the movements of subunit NqrC, which acts as an electron transfer switch. We propose that this switching movement controls the release of Na+ from a binding site localized in subunit NqrB.