The pattern of growth hormone action in the mouse brain.

Growth hormone (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 intraperitoneal 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, as 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.

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.

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.

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.

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.

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.

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.

A density functional theory benchmark on antioxidant-related properties of polyphenols.

In this work, we present a density functional theory benchmark on antioxidant-related properties for a series of six polyphenols that are well-known antioxidants: caffeic acid, cyanidin, ellagic acid, gallic acid, myricetin, and phloretin. Computations on the 24 O-H bond dissociation enthalpies (BDEs) and 6 ionization potentials (IPs) were performed using twenty-three exchange-correlation functionals combined with four different basis sets in the gas-phase, water, and methanol; calibration against the Domain-based Local Pair Natural Orbital CCSD(T) (DLPNO-CCSD(T)) approach was employed. Mean absolute deviation (MAD) as well as linear fitting results suggested the LC-PBE approach as the most suitable for O-H BDEs in the gas-phase. The LC-PBE, M06-2X, and M05-2X results presented the smallest MADs for O-H BDEs when compared to the reference, in water. The LC-PBE results had the smallest MADs for IPs in the gas-phase while M05-2X, M06-2X, LC-PBE, and LC-ωPBE exhibited the best results for MAD in water. We expect the outcomes from the present work will serve as general guidance for researchers working in the field.

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.

The Impact of Time From Diagnosis to Initiation of Chemotherapy on Survival of Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma in the Veterans Health Administration.

INTRODUCTION: Our retrospective study evaluates the impact of time from diagnosis to treatment (TDT) on outcomes of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated within the Veterans Health Administration (VHA). METHODS: VHA patients diagnosed with DLBCL between 2011 and 2019 were included, while those with primary central nervous system lymphoma were excluded. The median overall survival and progression-free survival were estimated with the Kaplan-Meier method. Univariate, bivariate, and multivariable analyses were performed using the Cox proportional hazards model. The odds ratio for refractory outcomes was calculated using logistic regression. RESULTS: A total of 2448 patients were included. The median time from diagnosis to treatment of the cohort was 19 days. When comparing median progression-free survival, median overall survival, and the 2-year overall survival between the group that started treatment within 1 week and each of the other groups individually, there was a significant difference favoring improved survival in all groups with a TDT longer than 1 week (P < .0001). These patients also had a lower odds ratio for refractory outcomes. On multivariable analysis, TDT remained an independent prognostic factor. CONCLUSION: Our study shows that a TDT equal to or less than 1 week is associated with adverse clinical factors, worse outcomes, and response in DLBCL, even after adjusting for multiple known poor prognostic factors. This was the first time that response to first-line therapy was correlated to time to treatment. Our findings support ongoing efforts to improve currently standardized prognostic tools and the incorporation of TDT into clinical trials to avoid selection bias.

Acute effects of foam rolling on ankle dorsiflexion and squat exercise patterns in extreme conditioning program practitioners: A randomized clinical trial.

BACKGROUND/OBJECTIVES: Joint and muscle overloads commonly occur in extreme conditioning programs (ECP), which require great physical fitness for their practice. For its execution, good functional performance, mobility and adequate movement patterns are required. The fascial system plays a fundamental role in performance in ECP and one of the techniques used to improve joint mobility and movement pattern is the self-myofascial release using a foam roller (FR). Our objective of this study was to evaluate the effect of FR in ankle dorsiflexion (DF) range of motion (ROM), assessed with the Lunge Test, and also in the squat movement pattern, assessed using the Technique smartphone application, in ECP practitioners. METHODS: The study was carried out with 18 ECP practitioners who practiced for over four months and had a mean age of 30.94 years. The participants were randomized and allocated into two groups: control and intervention. The FR was self-applied bilaterally in the sural triceps region for 90 seconds. Tests to assess DF ROM and squat movement pattern were applied before and immediately after using FR (intervention group) or after three-minute rest (control group). RESULTS: The use of the FR promoted an immediate increase in ankle DF ROM during the Lunge Test and during the squat and a decrease in dynamic knee valgus during the squat. CONCLUSION: The FR can be used as a tool for an acute increase in DF ROM and a decrease in dynamic knee valgus, having a positive impact in improving movement patterns.

Impact of access cavities on root canal preparation, restorative protocol quality, and fracture resistance of teeth.

The survival of endodontically treated teeth depends on the remaining tooth structure. The aim of this study was to evaluate the impact of different access cavities on root canal preparation, restorative protocol, and fracture resistance of endodontically treated teeth. Fifty-six mandibular molars were divided into control (n=8) and experimental (n=16) groups according to access cavity: Traditional, Conservative, and Truss; and redistributed (n=8) according to instrumentation protocols: Reciproc Blue and R-motion. After, teeth were scanned in micro-CT and then filled and redistributed according to composite resin restoration (n=8): Filtek One BulkFill and Filtek Z350. A new micro-CT scan was performed to analyze the restorative material. Then, samples were submitted to fracture resistance testing and the failure pattern was determined. Data were analyzed using paired T-test, ANOVA, Tukey, and chi-square tests (α=0.05). In Truss, R-Motion promoted less transportation in different thirds of root canals. Higher percentages of voids (5.05%) and filling material (11.7%) were observed in Truss. Fracture resistance values were higher for the control group, followed by Truss, Conservative, and Traditional. The predominant failure pattern was type-II. In Truss, reciprocating instruments with smaller taper showed less canal transportation. Also, Truss provided higher values of fracture resistance, although it presented a higher percentage of voids and remaining filling material. Thus, in Truss, reciprocating files with smaller taper showed less canal transportation, and these cavities provided higher values of fracture resistance, although it presented a higher percentage of voids and remaining filling material.

Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study. / Papel Incremental da Classificação da New York Heart Association e dos Índices do Teste de Exercício Cardiopulmonar para Prognóstico na Insuficiência Cardíaca: um Estudo de Coorte.

BACKGROUND: Central Illustration : Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study LVEF: left ventricular ejection fraction; HR: hazard ratio; CI: confidence interval; NYHA: New York Heart Association; VO 2: oxygen consumption. BACKGROUND: The accuracy of the New York Heart Association (NYHA) classification to assess prognosis may be limited compared with objective cardiopulmonary exercise test (CPET) parameters in heart failure (HF). OBJECTIVE: To investigate the prognostic value of the NYHA classification in addition to Weber class. METHODS: Adult outpatients with HF undergoing CPET in a Brazilian tertiary care center were included. The physician-assigned NYHA class and the CPET-derived Weber class were stratified into "favorable" (NYHA I or II; Weber A or B) or "adverse" (NYHA III or IV; Weber C or D). Patients with one favorable class and one adverse class were defined as "discordant." The primary endpoint was time to all-cause mortality. A 2-sided p value < 0.05 was considered statistically significant. RESULTS: A total of 834 patients were included. Median age was 57 years; 42% (351) were female, and median left ventricular ejection fraction was 32%. Among patients with concordant NYHA and Weber classes, those with adverse NYHA and Weber classes had significantly higher all-cause mortality compared to those with favorable classes (hazard ratio [HR]: 5.65; 95% confidence interval [CI]: 3.38 to 9.42). Among patients with discordant classes, there was no significant difference in all-cause mortality (HR: 1.38; 95% CI: 0.82 to 2.34). In the multivariable model, increments in NYHA class (HR: 1.55 per class increase; 95% CI: 1.26 to 1.92) and reductions in peak VO 2 (HR: 1.47 per 3 ml/kg/min decrease; 95% CI: 1.28 to 1.70) significantly predicted mortality. CONCLUSIONS: Physician-assigned NYHA class and objective CPET measures provide complementary prognostic information for patients with HF.

Chemical and morphological analysis of dentin irradiated by different high-power lasers: a systematic review.

PURPOSE: This systematic review provides an overview of the main chemical and morphological alterations generated on dentin by different high-power lasers' irradiation. METHODS: The review was registered in PROSPERO (CRD42023394164) and PRISMA guidelines were followed. The search strategy was conducted on MEDLINE (PubMed), Embase (Elsevier), and Web of Science (Clarivate) databases. The eligibility criteria were established according to the PICOS strategy, focusing on in vitro and ex vivo studies that assessed the chemical and morphological changes in dentin using five high-power lasers: Nd:YAG (1064 nm), Er:YAG (2940 nm), Er, Cr:YSGG (2780 nm), diode (980 nm), and CO2 (10,600 nm). Publication range was from 2010 to 2022. Data was summarized in tables and risk of bias was assessed by QUIN tool. RESULTS: The search resulted in 2255 matches and 57 studies composed the sample. The methods most used to assess the outcomes were scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and Raman. The studies presented "medium" and "low" risk of bias. The laser prevalently identified was the Er:YAG laser, associated with dentin ablation, absence of smear layer, and exposed tubules. The Nd:YAG laser generated vitreous surface and thermal damage, such as carbonization and cracks. The other lasers caused an irregular surface and no adverse thermal effects. Regarding the chemical structure, only the Er,Cr:YSGG laser caused collagen matrix reduction. The effects found were more intense with higher dosimetry. CONCLUSION: Evidence available indicates that the irradiation of dentin with high-power lasers are related to morphological outcomes favorable to adhesive restorative procedures, with minimal changes in collagen matrix and mineral content. However, those observations should be carried carefully by clinicians and more clinical trials regarding the association of high-power laser irradiation and restorative procedure longevity are needed.

mTORC1 Signaling in AgRP Neurons Is Not Required to Induce Major Neuroendocrine Adaptations to Food Restriction.

Hypothalamic mTORC1 signaling is involved in nutrient sensing. Neurons that express the agouti-related protein (AgRP) are activated by food restriction and integrate interoceptive and exteroceptive signals to control food intake, energy expenditure, and other metabolic responses. To determine whether mTORC1 signaling in AgRP neurons is necessary for regulating energy and glucose homeostasis, especially in situations of negative energy balance, mice carrying ablation of the Raptor gene exclusively in AgRP-expressing cells were generated. AgRPΔRaptor mice showed no differences in body weight, fat mass, food intake, or energy expenditure; however, a slight improvement in glucose homeostasis was observed compared to the control group. When subjected to 5 days of food restriction (40% basal intake), AgRPΔRaptor female mice lost less lean body mass and showed a blunted reduction in energy expenditure, whereas AgRPΔRaptor male mice maintained a higher energy expenditure compared to control mice during the food restriction and 5 days of refeeding period. AgRPΔRaptor female mice did not exhibit the food restriction-induced increase in serum corticosterone levels. Finally, although hypothalamic fasting- or refeeding-induced Fos expression showed no differences between the groups, AgRPΔRaptor mice displayed increased hyperphagia during refeeding. Thus, some metabolic and neuroendocrine responses to food restriction are disturbed in AgRPΔRaptor mice.

Clinical performance of sealants under different humidity control conditions: a split-mouth 1-year randomized trial.

PURPOSE: Sealants are an effective method of prevention and treatment for early caries lesions. This study analyzed the 1-year clinical performance of resin-based and ionomeric sealants applied to permanent teeth under different humidity conditions. METHODS: The investigation was a triple-blind randomized clinical trial (RCT) with a four arms split-mouth design, divided according to the sealant protocol: (1) Resin-based sealant applied with rubber dam isolation, (2) Resin-based sealant applied with cotton rolls isolation, (3) Ionomeric sealant applied with rubber dam isolation and (4) Ionomeric sealant applied with cotton rolls isolation. Fifty-eight patients started the study (232 teeth), and 47 (188 teeth) remained until the 1-year recall. The modified USPHS criteria were used in the analyzes to investigate surface texture, retention and the presence of secondary caries lesions around the sealants; in the following periods: baseline, after 3, 6, 9, and 12 months by two calibrated examiners. Data were analyzed by the Mann-Whitney and Friedman tests. RESULTS: There was no difference between the types of sealants (p > 0.05). The type of humidity control influenced the superficial texture (p = 0.0012) and the retention of sealants (p = 0.0023). The sealant displacement was greater under cotton rolls isolation. Only one active caries lesion in enamel was found in the 9th month. CONCLUSION: It may be concluded that sealants effectively prevented caries, even when they were partially or totally lost, regardless of the material. The rubber dam isolation with a rubber dam promoted lower surface roughness and improved the retention rates. International Clinical Trials Registry Platform: #1111-1215-2832 (07/26/2018).

Characterization, Antimicrobial Activity, and Antioxidant Efficacy of a Pomegranate Peel Solution Against Persistent Root Canal Pathogens.

BACKGROUND: The limitations of dental irrigation solutions reinforce the need to explore novel bioactive compounds that are safer and biodegradable. This study aimed to prepare a 10% pomegranate peel solution (Punica granatum extract - PGE) and evaluate its antimicrobial and antioxidant effects for root canal treatment. METHODS: Lyophilized extracts (1g/10 mL) from pomegranate peels were prepared, and the punicalagin content was assessed by ultra-performance liquid chromatography using pure punicalagin (standard). The antimicrobial activity was tested against common persistent root canal pathogens by the agar diffusion method, minimum inhibitory concentration (MIC), and minimum bactericidal/fungicide concentration (MCB/MFC). The antioxidant activity (%AA) was assessed by the DPPH radical scavenging method. Data were analyzed by ANOVA and Tukey's test (α = 0.05). RESULTS: The total phenolic content of the PGEextract was 6.55 µg/mL. Differences were found among the inhibition zone of PGE (23.32 ± 3.65), 1% NaOCl (30.76 ± 4.73), and 50% ethanol (without inhibition) (p < 0.05). The MIC values of PGE ranged between 6.25 and 75 mg/ml, and PGE was effective against the tested pathogens. PGE had antioxidant potential (IC50 = 3.52 µg/mL); however, the mean values were inferior to that of the quercetin (positive control) (IC50 = 0.95 µg/mL). The DPPH scavenging effect (%AA) of PGE (70.98 ± 2.3) had no difference from the positive control (72.94 ± 2.1) (p = 0.253). CONCLUSION: The PGE extract was successfully biosynthesized and exhibited antimicrobial and antioxidant activity, suggesting its potential use as an adjuvant therapy during root canal treatment.