Effect of the calcium silicate and sodium phosphate remineralizing products on bleached enamel.

Context and Aims: This study evaluated the effect of calcium silicate and sodium phosphate (CSSP) dentifrice and serum on the surface of enamel bleached with hydrogen peroxide (H2O2). Materials and Methods: A total of 160 bovine enamel slabs were bleached with 35% H2O2 and treated with sodium fluoride (NaF) dentifrice-GI, CSSP dentifrice-GII; CSSP dentifrice + CSSP serum-GIII, or NaF dentifrice + NaF gel-GIV. The dentifrices were applied using a brushing machine three times daily for 7 days. After brushing, sodium phosphate gel and CSSP serum were applied. The microhardness (KNH, n = 14), surface roughness (Ra, n = 14), energy dispersive spectroscopy (n = 6), and scanning electron microscopy (n = 6) were assessed at t0 (before bleaching), t1 (after bleaching), and t2 (after postbleaching treatments). Statistical Analysis Used: The data were subjected to a two-way analysis of variance and Bonferroni's test. Results: The KNH decreased at t1 (P < 0.001) but recovered at t2 for all treatments, although only GII showed restored baseline values (P = 0.0109). The surface roughness increased at t1 (P < 0.001) and reduced at t2 (P < 0.001) for all groups, with no significant differences among groups. Enamel composition and morphology did not differ after the treatments, except for silicon accumulation in GIII. Conclusions: Postbleaching treatment with CSSP dentifrice and serum yielded superior remineralizing effects on bleached enamel.

Assessing the Risk Stratification of Breast Cancer Polygenic Risk Scores in a Brazilian Cohort.

Polygenic risk scores (PRSs) for breast cancer have a clear clinical utility in risk prediction. PRS transferability across populations and ancestry groups is hampered by population-specific factors, ultimately leading to differences in variant effects, such as linkage disequilibrium and differences in variant frequency (allele frequency differences). Thus, locally sourced population-based phenotypic and genomic data sets are essential to assess the validity of PRSs derived from signals detected across populations. Here, we assess the transferability of a breast cancer PRS composed of 313 risk variants (313-PRS) in a Brazilian trihybrid admixed ancestries (European, African, and Native American) whole-genome sequenced cohort, the Rare Genomes Project. We computed 313-PRS in the Rare Genomes Project (n = 853) using the UK Biobank (UKBB; n = 264,307) as reference. We show that although the Brazilian cohorts have a high European ancestry (EA) component, with allele frequency differences and to a lesser extent linkage disequilibrium patterns similar to those found in EA populations, the 313-PRS distribution is inflated when compared with that of the UKBB, leading to potential overestimation of PRS-based risk if EA is taken as a standard. Interestingly, we find that case controls lead to equivalent predictive power when compared with UKBB-EA samples with area under the receiver operating characteristic curve values of 0.66 to 0.62 compared with 0.63 for UKBB.

Efficiency of the photodynamic therapy on viability of Streptococcus mutans in the oral cavity using chitosan nanoparticles: an in vitro study.

PURPOSE: This study aimed to investigate the efficiency of antimicrobial photodynamic therapy (aPDT) on Streptococcus mutans biofilm in the oral cavity using the photosensitizer chloroaluminum phthalocyanine encapsulated in chitosan nanoparticles (ClAlPc/Ch) at three preirradiation times. METHODS: Biofilms of Streptococcus mutans strains (ATCC 25,175) were cultivated on bovine tooth blocks and exposed to a 10% sucrose solution three times a day for 1 min over three consecutive days. The samples were randomly distributed into five treatment groups (n = 5): (I) aPDT with ClAlPc/Ch with a preirradiation time of 5 min (F5), (II) aPDT with ClAlPc/Ch with a preirradiation time of 15 min (F15), (III) aPDT with ClAlPc/Ch with a preirradiation time of 30 min (F30), (IV) 0.12% chlorhexidine digluconate (CHX), and (V) 0.9% saline solution (NaCl). After treatment, the S. mutans biofilms formed on each specimen were collected to determine the number of viable bacteria (colony-forming units (CFU)/mL). Data were analyzed for normality using the Shapiro-Wilk test and the analysis of variance (ANOVA) and Tukey HSD tests to analyze the number of viable bacteria (α = 0.05). RESULTS: The one-way ANOVA showed a difference between the groups (p = 0.0003), and the Tukey HSD posttest showed that CHX had the highest microbial reduction of S. mutans, not statistically different from the F5 and F15 groups, whereas the NaCl group had the lowest microbial reduction statistically similar to the F30 group. CONCLUSION: The results demonstrate that aPDT mediated by ClAlPc/Ch when used at preirradiation times of 5-15 min can be an effective approach in controlling cariogenic biofilm of S. mutans, being an alternative to 0.12% CHX.

Morphological characteristics of non-carious cervical lesions. A systematic review.

OBJECTIVES: This systematic review assessed the morphological characteristics of non-carious cervical lesions (NCCL), among clinical and ex-vivo studies assessed by observational and imaging methods. DESIGN: The search strategy was conducted on four online databases (MEDLINE, Embase, Scopus and Web of Science) and grey literature (Google Scholar and OpenGrey). The study selection was performed by three reviewers from March to September (2023). The eligibility criteria were established according to the PICO strategy and included NCCL, morphological characteristics and clinical and ex-vivo study designs. The data extraction considered general data that identifies the study, evaluation method, parameter to assess the outcome and the main results for each study. The risk of bias was evaluated using Joanna Briggs Institute critical appraisal tool, and a personalized tool. RESULTS: The search resulted in 252 studies. A total of 14 studies were included. Prevalence of NCCLs ranged from 3.5 %to 77.78 % with a higher presence in premolars. Common characteristics were wear facets, occluded tubules or cracks, occlusal stress, scratch marks, dimples and craters, structure loss, and dentin sclerosis, which appear more often on buccal surface and were generally classified as wedge-shaped, saucer-shaped. Etiological hypothesis was mainly related to multifactorial factors. In most of the studies, the risk of bias was classified as high. CONCLUSIONS: The morphological characteristics of NCCL showed a wide range of descriptions regarding appearance, prevalence, lesion-related measures, and macro and microscopic descriptions.

A fluorescence-based method to reaccess root canals in endodontically treated teeth: a MicroCT tridimensional assessment.

AIM: To evaluate the volume of dentin removal and volume of remnants of restorative material after removal of aesthetical restorative coronal set and cervical barrier in endodontically treated mandibular molars with aid of different magnification methods, using 3D MicroCT morphometric analysis. METHODS: A sample of 30 mandibular first molars (n=30) were used. All teeth were endodontic treated, and the specimens were initially scanned in MicroCT and reconstructed. The molars were filled by single cone technique, and immediately the material at the initial 2 mm cervical level were removed. Cervical barriers were confected using ionomer glass cement added with fluorescein 0.1%, filling the 2 mm at the cervical level of the canals and 2 additional millimeters as base. Coronal restoration set was performed using aesthetical resin composites. Simulated tooth aging process was performed with 20,000 thermocycling cycles. The sample was distributed in three groups (n=10) for the removal of the restoration set and cervical barrier with diamond burs based on the magnification aid: No magnification aid (naked-eye); Operative microscope aid; REVEAL™ device aid. After removal, final 3D MicroCT scanning and reconstruction were conducted with same parameters as the initial, and superposition of final and initial scanning was done. Morphometric analysis was conducted using CTAn to assess volume of remnant restorative material (mm³), volume of dentin removal (mm³), and the direction and site of dentin removal. Data were analyzed using One-Way ANOVA (p<0.05). RESULTS: REVEAL™ group showed better results regarding the volume of remnant material (3.17 ± 1.65) and the percentage of dentin removal (2.56 ± 1.34). Microscope group showed no statistical difference to the REVEAL™ group of dentin removal (3.30 ± 1.48), and was statistically similar to the naked eye group in volume of remnant material (9.63 ± 4.33). Naked eye group showed the worst results for volume of remnant material (7.60 ± 2.68) and percentage of dentin removal (6.60 ± 3.70). CONCLUSION: The use of fluorescence associated with magnification was the method that presented the best results, with lower percentages of dentin removal and smaller volumes of remaining restorative material. This is an innovative technology in Endodontics that shows potential to overdue the challenge of re-accessing root canals in the context of endodontic retreatment.

Analgesia by fascia manipulation is mediated by peripheral and spinal adenosine A1 receptor in a mouse model of peripheral inflammation.

The role of adenosine receptors in fascial manipulation-induced analgesia has not yet been investigated. The purpose of this study was to evaluate the involvement of the adenosine A1 receptor (A1R) in the antihyperalgesic effect of plantar fascia manipulation (PFM), specifically in mice with peripheral inflammation. Mice injected with Complete Freund's Adjuvant (CFA) underwent behavioral, i.e. mechanical hyperalgesia and edema. The mice underwent PFM for either 3, 9 or 15 min. Response frequency to mechanical stimuli was then assessed at 24 and 96 h after plantar CFA injection. The adenosinergic receptors were assessed by systemic (intraperitoneal, i.p.), central (intrathecal, i.t.), and peripheral (intraplantar, i.pl.) administration of caffeine. The participation of the A1R was investigated using the 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective A1R subtype antagonist. PFM inhibited mechanical hyperalgesia induced by CFA injection and did not reduce paw edema. Furthermore, the antihyperalgesic effect of PFM was prevented by pretreatment of the animals with caffeine given by i.p., i.pl., and i.t. routes. In addition, i.pl. and i.t. administrations of DPCPX blocked the antihyperalgesia caused by PFM. These observations indicate that adenosine receptors mediate the antihyperalgesic effect of PFM. Caffeine's inhibition of PFM-induced antihyperalgesia suggests that a more precise understanding of how fascia-manipulation and caffeine interact is warranted.

Feasibility of a Smartphone Application for Education and Symptom Management of Patients With Renal Cell Carcinoma on Combined Tyrosine Kinase and Immune Checkpoint Inhibitors.

PURPOSE: Patients with advanced renal cell carcinoma (RCC) face significant challenges, stemming both from the complexities of the disease itself and the adverse effects of treatments. This study evaluated the feasibility and acceptability of a mobile health (mHealth) application tailored for education and symptom management of patients with advanced RCC receiving combined immune checkpoint inhibitor and tyrosine kinase inhibitor (ICI-TKI) therapy. METHODS: The primary end points were acceptability and feasibility. Acceptability was defined as the proportion of patients approached who consented to participate, setting a benchmark of at least 50% for this metric. Feasibility was gauged by the completion rate of the intervention among the participants; it required at least 50% of participants to fully complete the intervention and at least 70% to finish half of the administered questionnaires. The secondary end points included knowledge assessment and patient-reported outcomes (PROs). PROs were evaluated using validated instruments. To discern the changes between pre- and post-educational module quiz scores, we used the Wilcoxon signed-rank test. Time-course data of PROs were visualized using line plots and then compared using paired t-tests. RESULTS: From November 2022 to July 2023, 20 of 22 (90%) patients approached for the study consented and enrolled. Of the enrolled patients, 60% completed all questionnaires and knowledge assessments at every time point and 75% completed at least half of the surveys and questionnaires. Significant pre/post differences were noted in two of six quizzes in the knowledge assessment. This study population did not experience a significant change in PRO scores after starting therapy. CONCLUSION: The mHealth application designed for education and symptom management in patients with advanced RCC undergoing combination ICI-TKI has proven to be both acceptable and feasible, meeting previous research benchmarks.

Probing the cw-Laser-Induced Fluorescence Enhancement in CsPbBr3 Nanocrystal Thin Films: An Interplay between Photo and Thermal Activation.

Perovskite nanocrystals hold significant promise for a wide range of applications, including solar cells, LEDs, photocatalysts, humidity and temperature sensors, memory devices, and low-cost photodetectors. Such technological potential stems from their exceptional quantum efficiency and charge carrier conduction capability. Nevertheless, the underlying mechanisms of photoexcitation, such as phase segregation, annealing, and ionic diffusion, remain insufficiently understood. In this context, we harnessed hyperspectral fluorescence microspectroscopy to advance our comprehension of fluorescence enhancement triggered by UV continuous-wave (cw) laser irradiation of CsPbBr3 colloidal nanocrystal thin films. Initially, we explored the kinetics of fluorescence enhancement and observed that its efficiency (φph) correlates with the laser power (P), following the relationship φph = 7.7⟨P⟩0.47±0.02. Subsequently, we estimated the local temperature induced by the laser, utilizing the finite-difference method framework, and calculated the activation energy (Ea) required for fluorescence enhancement to occur. Our findings revealed a very low activation energy, Ea ∼ 9 kJ/mol. Moreover, we mapped the fluorescence photoenhancement by spatial scanning and real-time static mode to determine its microscale length. Below a laser power of 60 µW, the photothermal diffusion length exhibited nearly constant values of approximately (22 ± 5) µm, while a significant increase was observed at higher laser power levels. These results were ascribed to the formation of nanocrystal superclusters within the film, which involves the interparticle spacing reduction, creating the so-called quantum dot solid configuration along with laser-induced annealing for higher laser powers.

The Pattern of GH Action in the Mouse Brain.

GH acts in numerous organs expressing the GH receptor (GHR), including the brain. However, the mechanisms behind the brain's permeability to GH and how this hormone accesses different brain regions remain unclear. It is well-known that an acute GH administration induces phosphorylation of the signal transducer and activator of transcription 5 (pSTAT5) in the mouse brain. Thus, the pattern of pSTAT5 immunoreactive cells was analyzed at different time points after IP or intracerebroventricular GH injections. After a systemic GH injection, the first cells expressing pSTAT5 were those near circumventricular organs, such as arcuate nucleus neurons adjacent to the median eminence. Both systemic and central GH injections induced a medial-to-lateral pattern of pSTAT5 immunoreactivity over time because GH-responsive cells were initially observed in periventricular areas and were progressively detected in lateral brain structures. Very few choroid plexus cells exhibited GH-induced pSTAT5. Additionally, Ghr mRNA was poorly expressed in the mouse choroid plexus. In contrast, some tanycytes lining the floor of the third ventricle expressed Ghr mRNA and exhibited GH-induced pSTAT5. The transport of radiolabeled GH into the hypothalamus did not differ between wild-type and dwarf Ghr knockout mice, indicating that GH transport into the mouse brain is GHR independent. Also, single-photon emission computed tomography confirmed that radiolabeled GH rapidly reaches the ventral part of the tuberal hypothalamus. In conclusion, our study provides novel and valuable information about the pattern and mechanisms behind GH transport into the mouse brain.

The impact of race and ethnicity on diffuse large B-cell lymphoma outcomes within the veterans health administration (VHA).

We performed a retrospective chart review of 6266 randomly selected DLBCL patients treated in the VHA nationwide between 1/1/2011 and 12/31/2021. The 3178 patients who met inclusion criteria were predominantly male (97%) and white (75%). Median age of diagnosis for Black patients was 63 years vs 69 years for the entire cohort (p < 0.001). However, patients in each race/ethnicity subgroup presented with similar rates of stage I/II and III/IV disease, IPI score, cell of origin and HIT status. Outcomes analysis revealed similar treatment, response rates, median overall survival, and 1-, 3-, and 5-year survival across all subgroups. Hispanic patients had a 21% lower risk of death (HR = 0.79) than white patients, and Black patients had no significant difference in survival (HR = 0.98). This large retrospective study shows that when standard of care therapy is given within an equal access system, short-term treatment and survival outcomes are the same for all races.

Ironing out obesity.

Obesity is associated with dysfunctions in hypothalamic neurons that regulate metabolism, including agouti-related protein (AgRP)-expressing neurons. In a recent article, Zhang et al. demonstrated that either diet- or genetically induced obesity promoted iron accumulation specifically in AgRP neurons. Preventing iron overload in AgRP neurons mitigated diet-induced obesity and related comorbidities in male mice.

Longevity of composite restorations in posterior teeth placed by dental students: a 12-year retrospective study.

OBJECTIVES: To evaluate the longevity of resin composite restorations placed in posterior teeth by dental students, using data from electronic records from 2008 to 2019. MATERIALS AND METHODS: Demographic (gender and age) and clinical variables (dental group, position in dental arch, and the number of restored surfaces) were evaluated. The 5-year follow-up was assessed according to the day the restoration was placed. Kaplan-Meier curves were generated to calculate the annual failure rate. Data were analyzed by Chi-Square, Kruskal-Wallis, and Mann-Whitney tests (α = 0.05). RESULTS: In total, 3.883 records relative to return periodicity were analyzed. The final sample consisted of 900 restorations from 479 patients. The majority were females, aged between 31 and 60. In total, 256 failures were reported (success rate = 78%), showing an annual failure rate of 2.05%. The main reasons for failures were restoration replacement (55.5%), endodontics (21.9%), prosthetics (14.5%) and extraction (8.2%). There was a higher risk of failure in restorations involving three or more surfaces (p = 0.000) and in patients over 60 years (p < 0.001). In females (p = 0.030), molars (p = 0.044), and maxillary teeth (p = 0.038) failed in a shorter time. CONCLUSIONS: Resin composite restorations placed in permanent posterior teeth by dental students had high survival rates. The main reason for failure was the replacement of restorations. The age group and the number of restored surfaces significantly affected the success of the restorations. CLINICAL RELEVANCE: The electronic health records over 12 years showed that 78% of the resin restorations in posterior teeth placed by dental students were successful for a minimum of five years.

Probing Antioxidant-Related Properties for Phenolic Compounds.

In this work, properties related to antioxidant-potential mechanisms (such as the bond dissociation enthalpy, BDE, for the homolytic cleavage of the O-H bond and ionization energies, IEs) were determined for phenol, pyrocatechol, and gallic acid (GA). Both the protonated and deprotonated forms of GA were investigated. The Feller-Peterson-Dixon (FPD) composite method was employed with a variety of computational approaches, i.e., density functional theory, Möller-Plesset perturbation theory, and coupled-cluster-based methods, in combination with large correlation consistent basis sets with extrapolation to the complete basis set limit and consideration of core electron correlation effects. FPD results were compared to experimental and computational data available in the literature, presenting good agreement. For example, the FPD BDE (298 K) obtained for phenol, which was based on valence-correlated MP2/CBS calculations with contributions from correlating all electrons, was determined to be 87.56 kcal/mol, a value that is 0.42 kcal/mol lower than the result obtained in the most recent experiments, 87.98 ± 0.62. Calibration against coupled-cluster calculations was also carried out for phenol. We expect that the outcomes gathered here may help in establishing a general protocol for computational chemists that are interested in determining antioxidant-related properties for phenolic compounds with considerable accuracy as well as to motivate future IE measurements (particularly for GA) to be accomplished in the near future.

Assessing push-out bond strength in re-irradiated teeth: Universal resin cement performance in self-etch and self-adhesive modes.

OBJECTIVES: To investigate the effect of cumulative doses of radiation on the pushout bond strength (BS) of a universal resin cement used in the self-etch (SE) and self-adhesive (SA) modes to the intraradicular dentin. MATERIALS AND METHODS: Forty-eight human teeth were distributed into three groups (n = 16) according to the radiation therapy dose (RT): NoRT (no-radiotherapy), 70RT (70 Gy), and 70 + 70RT (70 Gy + 70 Gy). The teeth were redistributed into two subgroups (n = 8), according to the adhesive mode: SE (NoRT-SE, 70RT-SE, and 70 + 70RT-SE) and SA (NoRT-SA, 70RT-SA, and 70 + 70RT-SA). Data were statistically compared after BS test (ANOVA, Tukey's post hoc test, and Fisher's exact test). RESULTS: In the SA mode, BS was significantly higher in nonirradiated teeth compared with 70RT and 70 + 70RT (p < 0.0001). There were no significant differences between SE and SA modes in nonirradiated teeth (p = 0.14). In the 70RT group, SE mode increased BS compared with SA mode (p < 0.0001). Most specimens had adhesive and mixed failures in SA and SE modes, respectively. CONCLUSIONS: The universal resin cement in the SE mode had greater BS to the irradiated dentin. When teeth were re-irradiated, the universal resin cement had similar performance in terms of BS, regardless of the adhesive approach. CLINICAL SIGNIFICANCE: There is no research establishing a correlation between radiotherapy and its impact on the BS of a universal resin cement used in SE and SA modes to intraradicular dentin.

Comparing deep learning and pathologist quantification of cell-level PD-L1 expression in non-small cell lung cancer whole-slide images.

Programmed death-ligand 1 (PD-L1) expression is currently used in the clinic to assess eligibility for immune-checkpoint inhibitors via the tumor proportion score (TPS), but its efficacy is limited by high interobserver variability. Multiple papers have presented systems for the automatic quantification of TPS, but none report on the task of determining cell-level PD-L1 expression and often reserve their evaluation to a single PD-L1 monoclonal antibody or clinical center. In this paper, we report on a deep learning algorithm for detecting PD-L1 negative and positive tumor cells at a cellular level and evaluate it on a cell-level reference standard established by six readers on a multi-centric, multi PD-L1 assay dataset. This reference standard also provides for the first time a benchmark for computer vision algorithms. In addition, in line with other papers, we also evaluate our algorithm at slide-level by measuring the agreement between the algorithm and six pathologists on TPS quantification. We find a moderately low interobserver agreement at cell-level level (mean reader-reader F1 score = 0.68) which our algorithm sits slightly under (mean reader-AI F1 score = 0.55), especially for cases from the clinical center not included in the training set. Despite this, we find good AI-pathologist agreement on quantifying TPS compared to the interobserver agreement (mean reader-reader Cohen's kappa = 0.54, 95% CI 0.26-0.81, mean reader-AI kappa = 0.49, 95% CI 0.27-0.72). In conclusion, our deep learning algorithm demonstrates promise in detecting PD-L1 expression at a cellular level and exhibits favorable agreement with pathologists in quantifying the tumor proportion score (TPS). We publicly release our models for use via the Grand-Challenge platform.

Pomegranate extract on eroded dentin: antioxidant action, bond strength and morphology of the adhesive interface after aging.

Objectives: This study aimed to evaluate the effect of pomegranate solution (Punica granatum) on eroded dentin through antioxidant action, shear bond strength (SBS) and interface morphology. Materials and Methods: The 10% pomegranate peel extract was prepared by the lyophilization method. Punicalagin polyphenol was confirmed by high-performance liquid chromatography. Antioxidant activity was evaluated by capturing the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. For the SBS, 48 dentin fragments were divided into sound or eroded, and subdivided according to the pretreatment (n = 12): water or P. granatum. The surfaces were restored with self-etch adhesive and a bulk-fill resin (Ecosite; DMG). The SBS was done immediately (24 hours) and after thermal cycling + water storage (12 months). For scanning electron microscopy, 48 dentin fragments (24 sound and 24 eroded) received the same treatments as for SBS (n = 6), and they were analyzed after 24 hours and 12 months. Results: The P. granatum had antioxidant action similar (p = 0.246) to the phenolic standard antioxidants. After 24 hours, eroded dentin had lower SBS than sound dentin (p < 0.001), regardless of the pretreatment. After 12 months, P. granatum maintained the SBS of sound dentin (13.46 ± 3.42 MPa) and eroded dentin (10.96 ± 1.90 MPa) statistically similar. The lowest values were found on eroded dentin treated with water (5.75 ± 1.65 MPa) (p < 0.001). P. granatum on eroded dentin caused peritubular demineralization and hybrid layer with resin tags. Conclusions: The pomegranate extract had antioxidant action and preserved the adhesive interface of the eroded dentin.

Physicochemical and mechanical properties of preheated composite resins for luting ceramic laminates.

This study analyzed and compared the physicochemical and mechanical properties of preheated resin composite with light-cured resin cement for luting indirect restorations. 210 specimens of resin cement/resin composite were prepared according to preheating treatment heated (Htd) or not (NHtd). Light-cured resin cement (Variolink Veneer, Ivoclar), and resin composite (Microhybrid-Z100, 3 M; Nanohybrid-Empress direct, Ivoclar; and Bulk fill-Filtek One, 3 M) were used (n = 10). Resin cement specimens were not preheated. The response variables were (n = 10): film thickness, microhardness, liquid sorption and solubility. Data were analyzed by 2-way ANOVA and Tukey HSD post-test (α = 0.05). Bulk fill NHtd resin had the highest film thickness values (p < 0.001). Microhybrid and nanohybrid Htd resins had the smallest thicknesses and did not differ from the cement (p > 0.05). The highest microhardness values were found for Bulk fill NHtd and Bulk fill Htd resins. The nanohybrid and microhybrid Htd resins showed the lowest microhardness values, with no difference in cement (p > 0.05). For liquid sorption, there was no significant difference between the groups (p = 0.1941). The microhybrid Htd resin showed higher solubility values than the other materials (p = 0.0023), but it did not differ statistically from resin cement (p > 0.05). Preheating composite resins reduced the film thickness. After heating, nanohybrid and Bulk fill resins retained stable microhardness, sorption, and solubility values.

Multiplex Immunofluorescence Captures Progressive Immune Exhaustion with Advancing Penile Squamous Cell Cancer Stage.

Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis. Herein, we explored for the first time the immune microenvironment of 57 men with PSCC and how it varies with the presence of human papillomavirus (HPV) infection and across tumor stages using multiplex immunofluorescence of key immune cell markers. We observed an increase in the density of immune effector cells in node-negative tumors and a progressive rise in inhibitory immune players such as type 2 macrophages and upregulation of the PD-L1 checkpoint in men with N1 and N2-3 disease. There were no differences in immune cell densities with HPV status.

Bovine serum albumin nanoparticles containing Poly (I:C) can enhance the neutralizing antibody response induced by envelope protein of Orthoflavivirus zikaense.

Since the Orthoflavivirus zikaense (ZIKV) has been considered a risk for Zika congenital syndrome development, developing a safe and effective vaccine has become a high priority. Numerous research groups have developed strategies to prevent ZIKV infection and have identified the domain III of the ZIKV envelope protein (zEDIII) as a promising target. Subunit antigens are often poorly immunogenic, necessitating the use of adjuvants and/or delivery systems to induce optimal immune responses. The subject of nanotechnology has substantial expansion in recent years in terms of research and applications. Nanoparticles could be used as drug delivery systems and to increase the immunogenicity and stability of a given antigen. This work aims to characterize and validate the potential of a vaccine formulation composed of domain zEDIII and bovine serum albumin nanoparticles containing polyinosinic-polycytidylic acid (NPPI). NPPI were uptake in vitro by immature bone marrow dendritic cells and histological analysis of the skin of mice treated with NPPI showed an increase in cellularity. Immunization assay showed that mice immunized with zEDIII in the presence of NPPI produced neutralizing antibodies. Through the passive transfer of sera from immunized mice to ZIKV-infected neonatal mice, it was demonstrated that these antibodies provide protection, mitigating weight loss, clinical or neurological signs induced by infection, and significantly increased survival rates. Protection was further substantiated by the reduction in the number of viable infectious ZIKV, as well as a decrease in inflammatory cytokines and tissue alterations in the brains of infected mice. Taken together, data presented in this study shows that NPPI + zEDIII is a promising vaccine candidate for ZIKV.