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1.
J Adhes Dent ; 23(2): 159-165, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825429

RESUMO

PURPOSE: To evaluate the effect of inclusion of two dimethyl sulfoxide (DMSO) concentrations in simplified etch-and-rinse adhesives on dentin bonding durability after three years of water storage. MATERIALS AND METHODS: Forty-two caries-free third molars were divided into six experimental groups (n = 7) according to the following factors: 1) adhesive (Adper Single Bond 2 [SB], 3M Oral Care; Prime&Bond 2.1 [PB], Dentsply Sirona); 2) concentration of DMSO (control group: 0.0% DMSO; addition of 0.2% DMSO [0.2] and 2% DMSO [2.0]). After completing restoration, specimens were stored in water (37°C) for 24 h, sectioned into adhesive-dentin sticks (0.8 mm2), tested for microtensile bond strength (µTBS) at 0.5 mm/min, and examined for nanoleakage (NL) using SEM immediately thereafter or after three years of water storage. Data were subjected to a three-way repeated-measures ANOVA and Tukey's test (α = 0.05) for each property evaluated. RESULTS: After three years of water storage, for both adhesives, the incorporation of 2% DMSO maintained the µTBS when compared to immediate µTBS (p > 0.05). In general, SB resulted in a statistically significantly higher mean of µTBS compared to PB, independent of the DMSO concentration after water storage (p < 0.05). Furthermore, the amount of NL was lower and practically limited to the hybrid layer given the concentrations of 0.2% and 2% DMSO for both tested adhesives after three years. CONCLUSION: The incorporation of DMSO in simplified etch-and-rinse adhesives maintains the long-term stability of the dentin bond.


Assuntos
Colagem Dentária , Adesivos Dentinários , Dentina , Dimetil Sulfóxido , Teste de Materiais , Cimentos de Resina , Resistência à Tração , Água
2.
Radiother Oncol ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33838170

RESUMO

AIM: To identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi). MATERIALS AND METHODS: Analysis included the REQUITE PCa cohort that received external beam RT and was followed for 2 years. Late toxicity endpoints were: rectal bleeding, urinary frequency, haematuria, nocturia, decreased urinary stream. Among 43 literature-identified SNPs, the 30% most strongly associated with each toxicity were tested. SNP-SNP combinations (named SNP-allele sets) seen in ≥10% of the cohort were condensed into risk (RS) and protection (PS) scores, respectively indicating increased or decreased toxicity risk. Performance of RS and PS was evaluated by logistic regression. RS and PS were then combined into a single PRSi evaluated by area under the receiver operating characteristic curve (AUC). RESULTS: Among 1,387 analysed patients, toxicity rates were 11.7% (rectal bleeding), 4.0% (urinary frequency), 5.5% (haematuria), 7.8% (nocturia) and 17.1% (decreased urinary stream). RS and PS combined 8 to 15 different SNP-allele sets, depending on the toxicity endpoint. Distributions of PRSi differed significantly in patients with/without toxicity with AUCs ranging from 0.61 to 0.78. PRSi was better than the classical summed PRS, particularly for the urinary frequency, haematuria and decreased urinary stream endpoints. CONCLUSIONS: Our method incorporates SNP-SNP interactions when calculating PRS for radiotherapy toxicity. Our approach is better than classical summation in discriminating patients with toxicity and should enable incorporating genetic information to improve normal tissue complication probability models.

3.
Cancers (Basel) ; 13(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810047

RESUMO

Several studies have identified single-nucleotide polymorphisms (SNPs) associated with adverse effects in non-small-cell lung cancer (NSCLC) patients treated with radiation therapy. Here, using an independent cohort, we aimed to validate the reported associations. We selected 23 SNPs in 17 genes previously associated with radiation-induced oesophagitis for validation in a cohort of 178 Spanish NSCLC patients. Of them, 18 SNPs were finally analysed, following the methods described in the original published studies. Two SNPs replicated their association with radiation-induced oesophagitis (rs7165790 located in the BLM gene: odds ratio (OR) = 0.16, 95% CI = 0.04-0.65, p-value = 0.010; rs4772468 at FGF14: OR = 4.36, 95% CI = 1.15-16.46, p-value = 0.029). The SNP rs2868371 at HSPB1 was also validated but displayed an opposite effect to the formerly described (OR = 3.72; 95% CI = 1.49-9.25; p-value = 0.004). Additionally, we tested a meta-analytic approach including our results and the previous datasets reported in the referenced publications. Twelve SNPs (including the two previously validated) retained their statistically significant association with radiation-induced oesophagitis. This study strengthens the role of inflammation and DNA double-strand break repair pathways in the risk prediction of developing radiation-induced oesophagitis in NSCLC patients. The validated variants are good candidates to be evaluated in risk prediction models for patient stratification based on their radiation susceptibility.

4.
Nat Commun ; 12(1): 1236, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33623038

RESUMO

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10-180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.


Assuntos
Grupos Étnicos/genética , Herança Multifatorial/genética , Neoplasias da Próstata/genética , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Autorrelato
5.
Artigo em Inglês | MEDLINE | ID: mdl-33537947

RESUMO

BACKGROUND: Information is lacking on long-term management of patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2). OBJECTIVES: Our objectives were to describe antithrombotic management patterns and outcomes in patients with ACS with varying renal function from the EPICOR (long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients; NCT01171404) and EPICOR Asia (NCT01361386) studies. METHODS: EPICOR and EPICOR Asia were prospective observational studies of patients who survived hospitalization for ACS and were enrolled at discharge in 28 countries across Europe, Latin America, and Asia. The studies were conducted from 2010 to 2013 and from 2011 to 2014, respectively. This analysis evaluated patient characteristics and oral antithrombotic management patterns and outcomes up to 2 years post-discharge according to admission eGFR: ≥ 90, 60-89, 30-59, or < 30 mL/min/1.73 m2. RESULTS: Among 22,380 patients with available data, eGFR < 60 mL/min/1.73 m2 was observed in 16.7%. Patients with poorer renal function were older, were at greater cardiovascular risk, and had more prior cardiovascular disease and bleeding. Patients with CKD underwent fewer cardiovascular interventions and had more in-hospital cardiovascular and bleeding events. Dual antiplatelet therapy was less likely at discharge in patients with eGFR < 30 (82.3%) than in those with ≥ 90 (91.3%) mL/min/1.73 m2 and declined more sharply during follow-up in patients with low eGFR (p < 0.0001). An adjusted proportional hazards model showed that patients with lower eGFR levels had a higher risk of cardiovascular events and bleeding. CONCLUSIONS: The presence of CKD in patients with ACS was associated with less aggressive cardiovascular management and an increased risk of cardiovascular events.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33420416

RESUMO

BACKGROUND: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). MATERIALS AND METHOD: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy. RESULTS: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer. CONCLUSIONS: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

7.
Methods Mol Biol ; 2174: 19-29, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32813242

RESUMO

Glioblastomas (GBM) are the most frequent and aggressive brain tumors due to their recurrence and resistance to current therapies. These characteristics are associated with the presence of glioma stem cells (GSCs), mainly identified by the detection of the membrane antigens CD133 and CD15. The main source of GSCs has been biopsies of tumors. However, alternatives are sought from cell lines because more homogeneous populations can be obtained with high yields. This chapter describes a method for the enrichment and characterization of GSCs from cell lines derived from human GBM by selective culture with serum-free neural stem cell medium and growth factors. The technique offers alternatives for the enrichment and characterization of GSCs, that could contribute to a better understanding of the biology of GBMs.

8.
Caries Res ; 55(1): 55-62, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33326969

RESUMO

The aim of this multicenter randomized clinical trial was to evaluate the pulp vitality and survival rate of adhesive restorations performed on posterior deciduous teeth after non-selective (NSCR) or selective (SCR) carious tissue removal over 33 months. One hundred and seven children (average age 4-8 years, SD 1.4) with at least two active moderate cavitated lesions in dentin were included. Teeth were randomized and submitted to NSCR or SCR before composite resin restoration. Restorations were clinically and radiographically assessed at baseline, 6, 12, 18, 24, and 33 months by a blinded, trained, and calibrated operator in each center. The characteristics of the restorations were recorded according to FDI criteria and were considered as restorative failures when scores 4 or 5 were presented. Pulp vitality was measured by clinical and radiographic examinations, and those teeth that presented any signs or symptoms of irreversible pulpitis or pulp necrosis were considered as failure. Data were analyzed by a Cox regression model with shared frailty, considering two outcomes: pulp and restorative. A total of 278 restorations (137 after NSCR and 141 after SCR) were performed at baseline in four different centers and there was no loss in the follow-up period. Survival rate was 97.1 and 87.1% for pulp and for restorative outcome, respectively. The overall annual failure rate was 7%. There were no differences in the failure risk according to the treatment group, center, and all the clinical and demographic variables, regardless of outcome. Composite restorations of active moderate deep carious lesions performed on posterior primary teeth show satisfactory survival for restorative and pulp outcome after a 33-month follow-up, regardless of the technique executed for carious tissue removal.

9.
Clin Chem ; 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33280026

RESUMO

BACKGROUND: Gene panel testing by massive parallel sequencing has increased the diagnostic yield but also the number of variants of uncertain significance. Clinical interpretation of genomic data requires expertise for each gene and disease. Heterozygous ATM pathogenic variants increase the risk of cancer, particularly breast cancer. For this reason, ATM is included in most hereditary cancer panels. It is a large gene, showing a high number of variants, most of them of uncertain significance. Hence, we initiated a collaborative effort to improve and standardize variant classification for the ATM gene. METHODS: Six independent laboratories collected information from 766 ATM variant carriers harboring 283 different variants. Data were submitted in a consensus template form, variant nomenclature and clinical information were curated, and monthly team conferences were established to review and adapt American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria to ATM, which were used to classify 50 representative variants. RESULTS: Amid 283 different variants, 99 appeared more than once, 35 had differences in classification among laboratories. Refinement of ACMG/AMP criteria to ATM involved specification for twenty-one criteria and adjustment of strength for fourteen others. Afterwards, 50 variants carried by 254 index cases were classified with the established framework resulting in a consensus classification for all of them and a reduction in the number of variants of uncertain significance from 58% to 42%. CONCLUSIONS: Our results highlight the relevance of data sharing and data curation by multidisciplinary experts to achieve improved variant classification that will eventually improve clinical management.

10.
Breastfeed Med ; 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33351698

RESUMO

The amount of milk production in mothers of babies admitted to the neonatal intensive care unit (NICU) is mostly determined by some actions focused on the first hours and days after birth. Working for an improvement in our previous results in terms of maternal expressed breast milk (MEBM) production, we designed a pilot project and a small observational study. After increasing the number of breast milk pumps to allow full-time availability and implementing educational strategies and updated information for parents, the volume of MEBM production by day 14 after birth was doubled and increased to >500 mL per day. The rate of exclusive breastfeeding at discharge improved from 26.67% to 76.19%. The cost of the use of donor milk per patient decreased by 15.7%. This study is an example of a cost-beneficial quality improvement strategy. It demonstrates the importance of an optimal supply of breast milk pumps in NICU and educational interventions focused on enhancing MEBM production.

11.
BMC Infect Dis ; 20(1): 964, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33353546

RESUMO

BACKGROUND: Due to the lack of proven therapies, we evaluated the effects of early administration of tocilizumab for COVID-19. By inhibition of the IL-6 receptor, tocilizumab may help to mitigate the hyperinflammatory response associated with progressive respiratory failure from SARS-CoV-2. METHODS: A retrospective, observational study was conducted on hospitalized adults who received intravenous tocilizumab for COVID-19 between March 23, 2020 and April 10, 2020. RESULTS: Most patients were male (66.7%), Hispanic (63.3%) or Black (23.3%), with a median age of 54 years. Tocilizumab was administered at a median of 8 days (range 1-21) after initial symptoms and 2 days (range 0-12) after hospital admission. Within 30 days from receiving tocilizumab, 36 patients (60.0%) demonstrated clinical improvement, 9 (15.0%) died, 33 (55.0%) were discharged alive, and 18 (30.0%) remained hospitalized. Successful extubation occurred in 13 out of 29 patients (44.8%). Infectious complications occurred in 16 patients (26.7%) at a median of 10.5 days. After tocilizumab was administered, there was a slight increase in PaO2/FiO2 and an initial reduction in CRP, but this effect was not sustained beyond day 10. CONCLUSIONS: Majority of patients demonstrated clinical improvement and were successfully discharged alive from the hospital after receiving tocilizumab. We observed a rebound effect with CRP, which may suggest the need for higher or subsequent doses to adequately manage cytokine storm. Based on our findings, we believe that tocilizumab may have a role in the early treatment of COVID-19, however larger randomized controlled studies are needed to confirm this.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Receptores de Interleucina-6/antagonistas & inibidores , Insuficiência Respiratória/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/farmacologia , Estudos de Coortes , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Resultado do Tratamento
12.
Front Oncol ; 10: 575909, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33216838

RESUMO

Background: Acute skin toxicity is a common and usually transient side-effect of breast radiotherapy although, if sufficiently severe, it can affect breast cosmesis, aftercare costs and the patient's quality-of-life. The aim of this study was to develop predictive models for acute skin toxicity using published risk factors and externally validate the models in patients recruited into the prospective multi-center REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve QUalITy of lifE in cancer survivors) study. Methods: Patient and treatment-related risk factors significantly associated with acute breast radiation toxicity on multivariate analysis were identified in the literature. These predictors were used to develop risk models for acute erythema and acute desquamation (skin loss) in three Radiogenomics Consortium cohorts of patients treated by breast-conserving surgery and whole breast external beam radiotherapy (n = 2,031). The models were externally validated in the REQUITE breast cancer cohort (n = 2,057). Results: The final risk model for acute erythema included BMI, breast size, hypo-fractionation, boost, tamoxifen use and smoking status. This model was validated in REQUITE with moderate discrimination (AUC 0.65), calibration and agreement between predicted and observed toxicity (Brier score 0.17). The risk model for acute desquamation, excluding the predictor tamoxifen use, failed to validate in the REQUITE cohort. Conclusions: While most published prediction research in the field has focused on model development, this study reports successful external validation of a predictive model using clinical risk factors for acute erythema following radiotherapy after breast-conserving surgery. This model retained discriminatory power but will benefit from further re-calibration. A similar model to predict acute desquamation failed to validate in the REQUITE cohort. Future improvements and more accurate predictions are expected through the addition of genetic markers and application of other modeling and machine learning techniques.

13.
Cancers (Basel) ; 12(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158149

RESUMO

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

14.
Front Oncol ; 10: 541281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178576

RESUMO

Background: REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) is an international prospective cohort study. The purpose of this project was to analyse a cohort of patients recruited into REQUITE using a deep learning algorithm to identify patient-specific features associated with the development of toxicity, and test the approach by attempting to validate previously published genetic risk factors. Methods: The study involved REQUITE prostate cancer patients treated with external beam radiotherapy who had complete 2-year follow-up. We used five separate late toxicity endpoints: ≥grade 1 late rectal bleeding, ≥grade 2 urinary frequency, ≥grade 1 haematuria, ≥ grade 2 nocturia, ≥ grade 1 decreased urinary stream. Forty-three single nucleotide polymorphisms (SNPs) already reported in the literature to be associated with the toxicity endpoints were included in the analysis. No SNP had been studied before in the REQUITE cohort. Deep Sparse AutoEncoders (DSAE) were trained to recognize features (SNPs) identifying patients with no toxicity and tested on a different independent mixed population including patients without and with toxicity. Results: One thousand, four hundred and one patients were included, and toxicity rates were: rectal bleeding 11.7%, urinary frequency 4%, haematuria 5.5%, nocturia 7.8%, decreased urinary stream 17.1%. Twenty-four of the 43 SNPs that were associated with the toxicity endpoints were validated as identifying patients with toxicity. Twenty of the 24 SNPs were associated with the same toxicity endpoint as reported in the literature: 9 SNPs for urinary symptoms and 11 SNPs for overall toxicity. The other 4 SNPs were associated with a different endpoint. Conclusion: Deep learning algorithms can validate SNPs associated with toxicity after radiotherapy for prostate cancer. The method should be studied further to identify polygenic SNP risk signatures for radiotherapy toxicity. The signatures could then be included in integrated normal tissue complication probability models and tested for their ability to personalize radiotherapy treatment planning.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33037816

RESUMO

PURPOSE: The results of a study to determine the difference in HIV management with clinical pharmacist input in an adult psychiatric hospitalized patient population are reported. METHODS: Single-center, retrospective study of patients admitted to a psychiatric hospital on antiretroviral (ARV) medication(s) from October 2016 to March 2017 (phase I: no pharmacist involvement), October 2017 to March 2018 (phase II: partial pharmacist involvement), and November 2018 to January 2019 (phase III: consistent pharmacist involvement). Patients were excluded if less than 18 years of age, pregnant, incarcerated, or taking ARV medication(s) for non-HIV indications. The primary outcome was difference in appropriateness of ARV therapy prior to and during pharmacist involvement. Secondary outcomes were appropriateness of opportunistic infection (OI) prophylaxis, laboratory testing, and comprehensive HIV management. RESULTS: Thirty-seven patients were included per phase. An increased number of appropriate ARV regimens were initiated in phase II compared to phase I (62% vs 32%; P = 0.01) and in phase III compared to phase II (84% vs 62%; P = 0.036). Increased laboratory monitoring was seen with partial and consistent pharmacist involvement. Among the patients requiring OI prophylaxis, appropriate prophylaxis was initiated in more patients in phase III (57%) than in phase II (50%) or phase I (11%). More patients had comprehensive HIV management in phase II compared to phase I (38% vs 5%; P < 0.001) and in phase III compared to phase II (46% vs 38%; P = 0.48). CONCLUSION: Pharmacist involvement in HIV management in a psychiatric patient population increased appropriateness of ARV therapy, laboratory testing, and OI prophylaxis.

16.
Cell Mol Neurobiol ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068216

RESUMO

The striatum is innervated by histaminergic fibers and expresses a high density of histamine H3 receptors (H3Rs), present on medium spiny neurons (MSNs) and corticostriatal afferents. In this study, in sagittal slices from the rat dorsal striatum, excitatory postsynaptic potentials (EPSPs) were recorded in MSNs after electrical stimulation of corticostriatal axons. The effect of H3R activation and blockers of calcium and potassium channels was evaluated with the paired-pulse facilitation protocol. In the presence of the H3R antagonist/inverse agonist clobenpropit (1 µM), the H3R agonist immepip (1 µM) had no effect on the paired-pulse ratio (PPR), but in the absence of clobenpropit, immepip induced a significant increase in PPR, accompanied by a reduction in EPSP amplitude, suggesting presynaptic inhibition. The blockade of CaV2.1 (P/Q-type) channels with ω-agatoxin TK (400 nM) increased PPR and prevented the effect of immepip. The CaV2.2 (N-type) channel blocker ω-conotoxin GVIA (1 µM) also increased PPR, but did not occlude the immepip action. Functional KIR3 channels are present in corticostriatal terminals, and in experiments in which immepip increased PPR, the KIR3 blocker tertiapin-Q (30 nM) prevented the effect of the H3R agonist. These results indicate that the presynaptic modulation by H3Rs of corticostriatal synapses involves the inhibition of Cav2.1 calcium channels and the activation of KIR3 potassium channels.

18.
Breast Cancer Res ; 22(1): 108, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087180

RESUMO

BACKGROUND: The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. RESULTS: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. CONCLUSIONS: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening.

19.
Dental Press J Orthod ; 25(4): 59-67, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965388

RESUMO

OBJECTIVE: To compare the effectiveness of the pretreatment with sandblasting and deproteinization with NaOCl on bond strength (SBS), in situ conversion degree (CD) of brackets in fluorotic enamel, and enamel etching pattern. METHODS: A total of 90 non-carious maxillary premolars were used. The teeth were then assigned to six experimental groups according to: enamel surface (sound and fluorotic enamel); surface treatment (Regular etch with 37% phosphoric acid [RE]; 5.2% sodium hypochlorite + phosphoric acid [NaOCl + RE]; sandblasting + phosphoric acid [sandblasting + RE]). After storage in distilled water (37°C/24h), the specimens were tested at 1 mm/min until failure (SBS). Enamel-resin cement interfaces were evaluated for CD using micro-Raman spectroscopy. The enamel-etching pattern was evaluated under a scanning electron microscope. Data from SBS and in situ CD values were analyzed using ANOVA two-away and Tukey test (α=0.05). The enamel etching pattern was evaluated only qualitatively. RESULTS: For sound enamel, RE showed the highest SBS values, when compared to NaOCl + RE and Sandblasting + RE groups (p< 0.01). Regarding CD, only NaOCl + RE significantly compromised the mean DC, in comparison with other groups (p= 0.002). For fluorotic enamel, the Sandblasting + RE group significantly increased the mean SBS values, in comparison with RE group (p= 0.01) and no significant change was observed for CD (p> 0.52). CONCLUSIONS: The application of NaOCl or sandblasting associated to phosphoric acid improved the SBS of the brackets in fluorotic enamel without compromising the CD of the resin cement, with improving of enamel interprismatic conditioning.


Assuntos
Colagem Dentária , Braquetes Ortodônticos , Condicionamento Ácido do Dente , Cimentos Dentários , Esmalte Dentário , Teste de Materiais , Ácidos Fosfóricos , Cimentos de Resina , Resistência ao Cisalhamento , Propriedades de Superfície
20.
Open Forum Infect Dis ; 7(9): ofaa320, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32959015

RESUMO

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ) is responsible for coronavirus disease 2019 (COVID-19), a disease that had not been previously described and for which clinicians need to rapidly adapt their daily practice. The novelty of SARS-CoV-2 produced significant gaps in harmonization of definitions, data collection, and outcome reporting to identify patients who would benefit from potential interventions. Methods: We describe a multicenter collaboration to develop a comprehensive data collection tool for the evaluation and management of COVID-19 in hospitalized patients. The proposed tool was developed by a multidisciplinary working group of infectious disease physicians, intensivists, and infectious diseases/antimicrobial stewardship pharmacists. The working group regularly reviewed literature to select important patient characteristics, diagnostics, and outcomes for inclusion. The data collection tool consisted of spreadsheets developed to collect data from the electronic medical record and track the clinical course after treatments. Results: Data collection focused on demographics and exposure epidemiology, prior medical history and medications, signs and symptoms, diagnostic test results, interventions, clinical outcomes, and complications. During the pilot validation phase, there was <10% missing data for most domains and components. Team members noted improved efficiency and decision making by using the tool during interdisciplinary rounds. Conclusions: We present the development of a COVID-19 data collection tool and propose its use to effectively assemble harmonized data of hospitalized individuals with COVID-19. This tool can be used by clinicians, researchers, and quality improvement healthcare teams. It has the potential to facilitate interdisciplinary rounds, provide comparisons across different hospitalized populations, and adapt to emerging challenges posed by the pandemic.

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