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1.
Phys Rev Lett ; 131(22): 222502, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101341

RESUMO

Collinear laser spectroscopy was performed on the isomer of the aluminium isotope ^{26m}Al. The measured isotope shift to ^{27}Al in the 3s^{2}3p ^{2}P_{3/2}^{○}→3s^{2}4s ^{2}S_{1/2} atomic transition enabled the first experimental determination of the nuclear charge radius of ^{26m}Al, resulting in R_{c}=3.130(15) fm. This differs by 4.5 standard deviations from the extrapolated value used to calculate the isospin-symmetry breaking corrections in the superallowed ß decay of ^{26m}Al. Its corrected Ft value, important for the estimation of V_{ud} in the Cabibbo-Kobayashi-Maskawa matrix, is thus shifted by 1 standard deviation to 3071.4(1.0) s.

2.
Genomics ; 115(3): 110625, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37068644

RESUMO

Precise regulation of transcription in gene expression is critical for all aspects of normal organism form, fitness, and function and even minor alterations in the level, location, and timing of gene expression can result in phenotypic variation within and between species including evolutionary innovations and human disease states. Eukaryotic transcription is regulated by a complex interplay of multiple factors working both at a physical and molecular levels influencing this process. In Saccharomyces cerevisiae, the TF with the greatest number of putative regulatory targets is the essential gene Repressor Activator Protein 1 (RAP1). While much is known about the roles of Rap1 in gene regulation and numerous cellular processes, the response of Rap1 target genes to systematic titration of RAP1 expression level remains unknown. To fill this knowledge gap, we used a strain with a tetracycline-titratable promoter replacing wild-type regulatory sequences of RAP1 to systematically reduce the expression level of RAP1 and followed this with RNA sequencing (RNA-seq) to measure genome-wide gene expression responses. Previous research indicated that Rap1 plays a significant regulatory role in particular groups of genes including telomere-proximal genes, homothallic mating (HM) loci, glycolytic genes, DNA repair genes, and ribosomal protein genes; therefore, we focused our analyses on these groups and downstream targets to determine how they respond to reductions in RAP1 expression level. Overall, despite being known as both an activator and as a repressor of its target genes, we found that Rap1 acts as an activator for more target genes than as a repressor. Additionally, we found that Rap1 functions as an activator of ribosomal protein genes and a repressor for HM loci genes consistent with predictions from the literature. Unexpectedly, we found that Rap1 functions as a repressor of glycolytic enzyme genes contrary to prior reports of it having the opposite effect. We also compared the expression of RAP1 to five different genes related to DNA repair pathway and found that decreasing RAP1 downregulated four of those five genes. Finally, we found no effect of RAP1 depletion on telomere-proximal genes despite its functioning to silence telomeric repeat-containing RNAs. Together our results enrich our understanding of this important transcriptional regulator.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Humanos , Saccharomyces cerevisiae/genética , Fator de Transcrição AP-1/genética , Proteínas de Saccharomyces cerevisiae/genética , Complexo Shelterina , Proteínas de Ligação a Telômeros/genética , Proteínas de Ligação a Telômeros/metabolismo , Proteínas Ribossômicas/genética , Expressão Gênica , Regulação Fúngica da Expressão Gênica , Proteínas Fúngicas/genética , Fatores de Transcrição/metabolismo
3.
Sci Rep ; 13(1): 4783, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36959230

RESUMO

High-precision hyperfine structure measurements were performed on stable, singly-charged [Formula: see text]Co ions at the IGISOL facility in Jyväskylä, Finland using the collinear laser spectroscopy technique. A newly installed light collection setup enabled the study of transitions in the 230 nm wavelength range from low-lying states below 6000 cm[Formula: see text]. We report a 100-fold improvement on the precision of the hyperfine A parameters, and furthermore present newly measured hyperfine B paramaters.

4.
BMC Cancer ; 22(1): 1258, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463104

RESUMO

BACKGROUND: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. METHODS: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. RESULTS: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. CONCLUSION: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. TRIAL REGISTRATION: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Antígeno B7-H1 , Mama , Neoplasias da Mama/tratamento farmacológico , Gencitabina
5.
Actas urol. esp ; 46(5): 275-284, jun. 2022. tab
Artigo em Espanhol | IBECS | ID: ibc-208675

RESUMO

Objetivos Evaluar los resultados de la prostatectomía radical asistida por robot (PRAR), y compararlos con los de la cirugía abierta (PRA) y laparoscópica (PRL). El interés no solo radica en los resultados oncológicos y funcionales de la serie, sino en la evaluación de la calidad de vida (QoL), la recuperación postoperatoria y la satisfacción personal de los pacientes con la intervención (PR), fundamentalmente. Métodos Se realizaron 685 PR en nuestro centro entre 2011-2018 (17,8% PRA, 22,2% PRL y 60% PRAR). Los pacientes fueron evaluados prospectivamente mediante seguimiento hasta abril de 2020, y con la realización un cuestionario múltiple a los 12 meses post-PR, que incluía ICIQ-SF, SHIM, IPSS, IQL y preguntas sobre el dolor, la recuperación postoperatoria y la satisfacción del paciente (SP). También se recogieron datos basales y postoperatorios relacionados con el paciente y el tratamiento, y se realizaron regresiones logísticas binomiales para las comparaciones 1 vs. 1 (PRA vs. PRAR y PRL vs. PRAR). Resultados Los pacientes tratados con PRAR tienen en general menos comorbilidades, menos agresividad tumoral, un requerimiento de mayor tiempo operatorio y un número mayor de márgenes quirúrgicos positivos que los pacientes tratados con PRA y PRL. Sin embargo, la PRAR supera a la PRA en: días de estancia hospitalaria (OR: 0,86; IC 95%: 0,80-0,94), disminución de hemoglobina (OR: 0,38; IC 95%: 0,30-0,47), tasas de transfusión (OR: 0,18; IC 95%: 0,09-0,34), complicaciones tempranas (p=0,001), IQL (OR: 0,82; IC 95%: 0,69-0,98), función eréctil (OR: 0,41; IC 95%: 0,21-0,79), manejo del dolor (OR: 0,82; IC 95%: 0,75-0,89), recuperación postoperatoria (p<0,001) y elección de un abordaje diferente (OR: 5,55; IC 95%: 3,14-9,80). La PRAR es superior a la PRL en: continencia urinaria (OR: 0,55; IC 95%: 0,37-0,82), IPSS (OR: 0,96; IC 95%: 0,93-0,98) (AU)


Objectives To evaluate the outcomes of robot-assisted radical prostatectomy (RARP) compared to those of open (ORP) and laparoscopic (LRP) surgery. The interest lies fundamentally in the quality-of-life (QoL) evaluation, postoperative recovery, and personal satisfaction of patients with the intervention (PS) beyond oncological and functional outcomes. Methods Six hundred eighty-five RPs were performed in our center between 2011-2018 (17.8% ORP, 22.2% LRP and 60% RARP). Patients were prospectively assessed through follow-up until April 2020 and a multiple questionnaire at 12-months post-RP that included ICIQ-SF, SHIM, IPSS, IQL and questions about pain, postoperative recovery and PS. Also baseline and postoperative patient- and treatment-related data were collected, and binomial logistic regressions were performed for the 1 vs. 1 comparisons (ORP vs. RARP and LRP vs. RARP). Results RARP patients have overall fewer comorbidities, less tumor aggressiveness, more operative time requirements and more positive surgical margins than ORP and LRP patients. Nevertheless, RARP outperforms ORP in: hospital say (days) (OR: 0.86; 95% CI: 0.80-0.94), hemoglobin loss (OR: 0.38; 95% CI: 0.30-0.47), transfusion rate (OR: 0.18; 95% CI: 0.09-0.34), early complications (P=.001), IQL (OR: 0,82; 95% CI: 0.69-0.98), erectile function (OR: 0.41; 95% CI: 0.21-0.79), pain control (OR: 0.82; 95% CI: 0.75-0.89), postoperative recovery (P<.001) and choice of a different approach (OR: 5.55; 95% CI: 3.14-9.80). RARP is superior to LRP in: urinary continence (OR: 0.55; 95% CI: 0.37-0.82), IPSS (OR: 0.96; 95% CI: 0.93-0.98), IQL (OR: 0.76; 95% CI: 0.66-0.88), erectile function (OR: 0.52; 95% CI: 0.29-0.93), postoperative recovery (P=.02 and .004), PS (P=.005; 0.002; and .03) and choice of a different approach (OR: 7.79; 95% CI: 4.63-13.13) (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Satisfação do Paciente , Qualidade de Vida , Estudos Prospectivos , Seguimentos , Resultado do Tratamento
6.
Phys Rev Lett ; 128(15): 152501, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35499902

RESUMO

The impact of nuclear deformation can been seen in the systematics of nuclear charge radii, with radii generally expanding with increasing deformation. In this Letter, we present a detailed analysis of the precise relationship between nuclear quadrupole deformation and the nuclear size. Our approach combines the first measurements of the changes in the mean-square charge radii of well-deformed palladium isotopes between A=98 and A=118 with nuclear density functional calculations using Fayans functionals, specifically Fy(std) and Fy(Δr,HFB), and the UNEDF2 functional. The changes in mean-square charge radii are extracted from collinear laser spectroscopy measurements on the 4d^{9}5s ^{3}D_{3}→4d^{9}5p ^{3}P_{2} atomic transition. The analysis of the Fayans functional calculations reveals a clear link between a good reproduction of the charge radii for the neutron-rich Pd isotopes and the overestimated odd-even staggering: Both aspects can be attributed to the strength of the pairing correlations in the particular functional which we employ.

7.
Actas Urol Esp (Engl Ed) ; 46(5): 275-284, 2022 06.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35260370

RESUMO

OBJECTIVES: To evaluate the outcomes of robot-assisted radical prostatectomy (RARP) compared to those of open (ORP) and laparoscopic (LRP) surgery. The interest lies fundamentally in the quality-of-life (QoL) evaluation, postoperative recovery, and personal satisfaction of patients with the intervention (PS) beyond oncological and functional outcomes. METHODS: Six hundred eighty-five RPs were performed in our center between 2011-2018 (17,8% ORP, 22,2% LRP and 60% RARP). Patients were prospectively assessed through follow-up until April 2020 and a multiple questionnaire at 12-months post-RP that included ICIQ-SF, SHIM, IPSS, IQL and questions about pain, postoperative recovery and PS. Also baseline and postoperative patient- and treatment-related data were collected, and binomial logistic regressions were performed for the 1 vs.1 comparisons (ORP vs. RARP and LRP vs. RARP). RESULTS: RARP patients have overall fewer comorbidities, less tumor aggressiveness, more operative time requirements and more positive surgical margins than ORP and LRP patients. Nevertheless, RARP outperforms ORP in: hospital stay (days) (OR 0,86; 95% CI: 0,80-0,94), hemoglobin loss (OR 0,38; 95% CI: 0,30-0,47), transfusion rate (OR 0,18; 95% CI: 0,09-0,34), early complications (p = 0,001), IQL (OR 0,82; 95% CI: 0,69-0,98), erectile function (OR 0,41; 95% CI: 0,21-0,79), pain control (OR 0,82; 95% CI: 0,75-0,89), postoperative recovery (p < 0,001) and choice of a different approach (OR 5,55; 95% CI: 3,14-9,80). RARP is superior to LRP in: urinary continence (OR 0,55; 95% CI: 0,37-0,82), IPSS (OR 0,96; 95% CI: 0,93-0,98), IQL (OR 0,76; 95% CI: 0,66-0,88), erectile function (OR 0,52; 95% CI: 0,29-0,93), postoperative recovery (p = 0,02 and 0,004), PS (p = 0,005; 0,002; and 0,03) and choice of a different approach (OR 7,79; 95% CI: 4,63-13,13). CONCLUSIONS: The findings of our study globally endorse a positive effectiveness of RARP over ORP and/or LRP, both on functional issues, postoperative recovery, QoL and PS. Oncologic results should still be improved.


Assuntos
Disfunção Erétil , Procedimentos Cirúrgicos Robóticos , Disfunção Erétil/etiologia , Humanos , Masculino , Prostatectomia/métodos , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
8.
Avian Dis ; 66(1): 106-111, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35308012

RESUMO

In the last decade, monitoring Marek's disease (MD) vaccination by real-time PCR has become a common practice. Evaluating in vivo replication of MD vaccines in the feather pulp (FP) at 7 days of age provides information on how well a flock has been vaccinated. Factors such as vaccine dose, combination with other vaccines, age and route of vaccination, and the origin of the vaccine can influence the results and need to be taken into consideration. Early infection with oncogenic MD virus (MDV) could also affect how vaccines replicate in the first week and therefore might influence the results. The objective of this study was to evaluate if coinfection with oncogenic MDV could affect MD vaccine DNA viral load in the FP at 7 days of age. A retrospective study was done using data from nine animal experiments (46 treatment groups) in which chickens were vaccinated against MD either in ovo or at 1 day of age and challenged with various oncogenic strains at 1 day of age by contact. In each experiment, vaccinated but not challenged groups were used as controls. Replication of MD vaccine was evaluated in samples of FP collected at 7 days of age by real-time PCR, and percentage of positives and vaccine load were analyzed. Our results show that CVI-988 (13 treatment groups), SB-1 (six treatment groups), and in most cases turkey herpesvirus (HVT; 24 out of 27 treatment groups) replication was not affected by early infection with oncogenic MDV. There were three treatment groups in which HVT replication differed between challenged and unchallenged chickens, however the effect was not clear; replication of HVT in nonchallenged chickens was higher (one treatment group) or lower (two treatment groups) than in challenged chickens and factors other than coinfection with MDV might have contributed to such differences.


Nota de investigación­El desafío temprano con un virus oncogénico de la enfermedad de Marek no interfiere con la carga de ADN de las vacunas contra la enfermedad de Marek en la pulpa de la pluma a los siete días de edad. En la última década, el seguimiento de la vacunación contra la enfermedad de Marek (EM) mediante PCR en tiempo real se ha convertido en una práctica común. La evaluación de la replicación in vivo de las vacunas de Marek en la pulpa de la pluma (FP) a los siete días de edad proporciona información sobre qué tan bien se ha vacunado una parvada. Factores como la dosis de la vacuna, la combinación con otras vacunas, la edad, la vía de vacunación y el origen de la vacuna pueden influir en los resultados y deben tenerse en cuenta. La infección temprana con un virus de Marek oncogénico (MDV) también podría afectar la forma en que las vacunas se replican en la primera semana y por lo tanto, podría influir en los resultados. El objetivo de este estudio fue evaluar si la coinfección con un virus de Marek oncogénico podría afectar la carga viral del ADN de la vacuna de Marek en la pulpa de la pluma a los siete días de edad. Se realizó un estudio retrospectivo utilizando datos de nueve experimentos con animales (46 grupos de tratamientos) en los que se vacunaron pollos contra la enfermedad de Marek ya sea in ovo o al día de edad y se desafiaron con varias cepas oncogénicas al día de edad por contacto. En cada experimento, se utilizaron como controles los grupos vacunados, pero no desafiados. Se evaluó la replicación de la vacuna de Marek en muestras de pulpa de la pluma recolectadas a los siete días de edad por PCR en tiempo real, y se analizó el porcentaje de positivos y la carga vacunal. Los resultados de este estudio muestran que la replicación de la cepa CVI-988 (13 grupos de tratamiento), la cepa SB-1 (seis grupos de tratamiento) y en la mayoría de los casos, del herpesvirus de pavo (HVT; 24 de 27 grupos de tratamiento) no se vio afectada por la infección temprana con un virus de Marek oncogénico. Hubo tres grupos de tratamiento en los que la replicación de la vacuna HVT difería entre pollos desafiados y no desafiados, sin embargo, el efecto no fue claro; la replicación de la vacuna HVT en pollos no desafiados fue mayor (un grupo de tratamiento) o menor (dos grupos de tratamiento) que en los pollos desafiados y otros factores distintos a la coinfección con el virus de la enfermedad de Marek podrían haber contribuido a tales diferencias.


Assuntos
Coinfecção , Herpesvirus Galináceo 2 , Vacinas contra Doença de Marek , Doença de Marek , Animais , Galinhas , Coinfecção/veterinária , DNA Viral , Plumas , Herpesvirus Galináceo 2/genética , Estudos Retrospectivos
9.
Medicina UPB ; 41(1): 80-84, mar. 2022.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1362715

RESUMO

El envenenamiento debido a picadora de escorpiones es reportado en diferentes países de Suramérica, en algunos, como México, es un problema de salud pública. En Colombia el accidente por escorpiones no es de reporte obligatorio, por lo que hay subregistro de casos. Los accidentes por este tipo de animales ponzoñosos se asocian a manifestaciones locales, y en casos de gravedad moderada a severa, a problemas cardiovasculares y neurológicos. Sin embargo, es importante reconocer manifestaciones que, aunque reportadas con menos frecuencia, implican gran morbilidad, como la pancreatitis y las alteraciones renales, entre las que está la nefritis. Se reporta el caso de un varón de 46 años, que presentó un accidente por Tytus, con nefritis intersticial. Este es el primer reporte de esta complicación en Colombia. Nuestro objetivo principal es resaltar la importancia de una pronta identificación de casos y un oportuno inicio del tratamiento por parte del personal de la salud, que permitan disminuir la morbilidad y mortalidad de estos pacientes.


Scorpion poisoning is reported in different countries in South America, especially in Mexico, where it has become a public health issue. In Colombia this type of accident is not mandatory to report, therefore, there is underreporting of cases. Accidents caused by these poisonous animals are mainly associated with local manifestations and, in cases of moderate to severe severity, to cardiovascular and neurological problems. Nevertheless, it is important to recognize other manifestations which, despite being reported less frequently, are associated with high morbidity such as pancreatitis and renal alterations, among which is nephritis. The case of a 46-year-old male patient is reported, who had an accident due to Tytus and presented interstitial nephritis. This is the first report of this complication in Colombia, and based on this, the main objective is to highlight the importance of prompt identification and treatment by health personnel, in order to reduce morbidity and mortality in these patients.


O envenenamento devido a picadora de escorpiões é reportado em diferentes países da América Latina, em alguns, como México, é um problema de saúde pública. Na Colômbiao acidente por escorpiões não é de reporte obrigatório, porque há sub-registro de casos. Os acidentes por este tipo de animais peçonhentos se associam a manifestações locais, e em casos de gravidade moderada a severa, a problemas cardiovasculares e neurológicos. Entretanto, é importante reconhecer manifestações que, embora reportadas com menos frequência, implicam grande morbilidade, como a pancreatite e as alterações renais, entre as que está a nefrite. Se reporta o caso de um homem de 46 anos, que apresentou um acidente por Tytus, com nefrite intersticial. Este é o primeiro reporte desta complicação na Colômbia. Nosso objetivo principal é ressaltar a importância de uma breve identificação de casos e um oportuno início do tratamento por parte do pessoal da saúde, que permitam diminuir a morbilidade e mortalidade destes pacientes.


Assuntos
Humanos , Animais , Escorpiões , Injúria Renal Aguda , Picadas de Escorpião , Animais Venenosos , Nefrite
10.
Talanta ; 243: 123304, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35202838

RESUMO

This work reports an amperometric bioplatform for the determination of anti-myelin basic protein autoantibodies (anti-MBP), a relevant biomarker for multiple sclerosis (MS) autoimmune disease. The developed configuration involves the use of carboxylated magnetic microparticles (cMBs) where the protein for specific capture of the target autoantibodies was covalently attached. The immobilized anti-MBP were further conjugated with a secondary antibody labelled with horseradish peroxidase (HRP-anti-hIgG) and amperometric transduction was performed by adding hydrogen peroxide and using hydroquinone (HQ) as redox mediator. The cathodic current resulting from the reduction of the corresponding quinone was directly proportional to the logarithmic concentration of the target autoantibodies. The analytical performance of the developed method for the determination of anti-MBP is competitive in terms of sensitivity and range of linearity with that claimed for the only biosensor reported so far in the literature, as well as with commercially available ELISA kits showing a remarkably shorter assay time. The bioplatform was applied to the analysis of serum samples of healthy individuals and patients diagnosed with MS providing results in agreement with the ELISA methodology.


Assuntos
Técnicas Biossensoriais , Esclerose Múltipla , Autoanticorpos , Técnicas Biossensoriais/métodos , Eletrodos , Ensaio de Imunoadsorção Enzimática , Humanos , Esclerose Múltipla/diagnóstico , Proteína Básica da Mielina
11.
J STEM Outreach ; 5(2)2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37179901

RESUMO

A cancer research training program explored different approaches for staffing their in-person and virtual programs for high school students. The inclusion of undergraduate near-peer mentors had a universal benefit when implemented across in-person and virtual training programs of one- and ten-week durations. Benefits are described for four stakeholder groups: the high school trainees, program staff, scientist partners, and peer mentors themselves. Peer mentors described that their involvement enhanced their own professional development and, for some, drove a new interest in cancer research. Scientist partners described that peer mentors helped translate their work in the virtual environment for high school students. High school trainees reported their sessions with peer mentors to be one of their favorite parts of the program. Interprofessional peer mentors were highly relatable to students and modeled communication and paths in biomedical research. Staff reported that peer mentors supported student engagement during community shadowing sessions, allowing staff to focus on developing the shadowing experiences with partners. The benefit of including peer mentors was substantial from all viewpoints explored. Their intensive inclusion in cancer research training programs supports sustainability and capacity building in biomedical workforce development.

12.
Nat Prod Res ; 36(4): 1123-1128, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33342288

RESUMO

Agave marmorata Roezl is an endemic succulent specie from the Oaxaca-Puebla area of Mexico. This plant is a medicinal recourse and contain a rich variety of saponins-type compounds with multiples biological effects. Some of them have been shown to be anticancer, antibacterial, or having anti-inflammatory and immunoregulation effects. This paper is the first scientific report to describe the pharmacological activity and chemistry of the saponin smilagenin-3-O-[ß-D-glucopyranosyl (1→2)-ß-D-galactopyranoside] (1), isolated from Agave marmorata Roezl. Saponin (1) displayed immunomodulating activity when assayed on cultured macrophages. It inhibits NO production (EC50 = 5.6 mg/ml, Emax = 101%), as well as NF-κB expression (EC50 = 0.086 mg/ml, Emax = 90%). Using bioinformatic molecular docking, we identified a new smilagenin- PI3K kinase interaction site.


Assuntos
Agave , NF-kappa B/antagonistas & inibidores , Saponinas , Fator de Transcrição AP-1/antagonistas & inibidores , Agave/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Saponinas/química , Saponinas/farmacologia
13.
Eur J Prosthodont Restor Dent ; 30(2): 107-112, 2022 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34304395

RESUMO

The purpose of this in-vitro study was to compare trueness, 3D deviation, production time and costs of milled and 3D-printed resin single crowns. A total of 20 CAD-CAM resin single crowns were fabricated from 10 digital wax patterns designed on 10 tooth preparations available in a reference model. Standardized control linear measurements were performed with a CAD software. Each STL file was then used to fabricate two resins crowns - one milled and one 3D-printed. All crowns underwent physical linear measurements using a digital caliper. The crowns were then scanned using an intraoral scanner for assessing 3D deviation. Finally, time to produce a single crown, as well as costs and production rates of both methods were also compared. Both CAM methods did not present statistically significant differences in linear measurements, as compared to controls (P⟩.05). Furthermore, 3D-printed crowns had significantly greater deviations in cervical margins (P=.032) and occlusal surfaces (P=.041), as compared with milled crowns. Finally, 3D-printing took significantly longer to produce one single crown (P=.001), but with a cheaper and higher production rate than milling. These findings suggest that milling devices produce resin single crowns with smaller 3D deviations but more expensive costs, as compared with low-cost 3D printers.


Assuntos
Desenho Assistido por Computador , Coroas , Custos e Análise de Custo , Adaptação Marginal Dentária , Planejamento de Prótese Dentária , Impressão Tridimensional , Software
14.
Braz. j. biol ; 82: e232525, 2022. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1249239

RESUMO

The coupling of a ligand with a molecular receptor induces a signal that travels through the receptor, reaching the internal domain and triggering a response cascade. In previous work on T-cell receptors and their coupling with foreign antigens, we observed the presence of planar molecular patterns able to generate electromagnetic fields within the proteins. These planes showed a coherent (synchronized) behavior, replicating immediately in the intracellular domain that which occurred in the extracellular domain as the ligand was coupled. In the present study, we examined this molecular transduction - the capacity of the coupling signal to penetrate deep inside the receptor molecule and induce a response. We verified the presence of synchronized behavior in diverse receptorligand systems. To appreciate this diversity, we present four biochemically different systems - TCR-peptide, calcium pump-ADP, haemoglobin-oxygen, and gp120-CD4 viral coupling. The confirmation of synchronized molecular transduction in each of these systems suggests that the proposed mechanism would occur in all biochemical receptor-ligand systems.


A ligação de um ligante com um receptor molecular induz um sinal que viaja através do receptor, chegando ao domínio interno e disparando uma cascata de resposta. Em trabalhos anteriores em receptores de células T e sua ligação com antígenos estranhos, observamos a presença de padrões moleculares planares capazes de gerar campos eletromagnéticos dentro das proteínas. Esses planos mostraram um comportamento coerente (sincronizado), replicando, instantaneamente, no domínio intracelular o que ocorreu no domínio extracelular, enquanto o ligante era acoplado. No presente estudo, examinamos essa transdução ­ a capacidade de um sinal de acoplamento de penetrar profundamente a molécula receptora e induzir uma resposta. Verificamos a presença de um comportamento coerente em sistemas diversos de receptor-ligante. Para apreciar essa diversidade, apresentamos quatro sistemas bioquímicos diferentes: TCR-peptídeo, ADP-bomba de cálcio, hemoglobina-oxigênio e gp120-CD4 acoplamento viral. A confirmação de transdução molecular sincronizada em cada um desses sistemas sugere que o mecanismo proposto ocorreria em todos os sistemas bioquímicos receptor-ligante.


Assuntos
Transdução de Sinais , Campos Eletromagnéticos , Receptores de Antígenos de Linfócitos T/genética , Ligantes
15.
Braz. j. biol ; 82: 1-10, 2022. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1468470

RESUMO

The coupling of a ligand with a molecular receptor induces a signal that travels through the receptor, reaching the internal domain and triggering a response cascade. In previous work on T-cell receptors and their coupling with foreign antigens, we observed the presence of planar molecular patterns able to generate electromagnetic fields within the proteins. These planes showed a coherent (synchronized) behavior, replicating immediately in the intracellular domain that which occurred in the extracellular domain as the ligand was coupled. In the present study, we examined this molecular transduction - the capacity of the coupling signal to penetrate deep inside the receptor molecule and induce a response. We verified the presence of synchronized behavior in diverse receptor ligand systems. To appreciate this diversity, we present four biochemically different systems - TCR-peptide, calcium pump-ADP, haemoglobin-oxygen, and gp120-CD4 viral coupling. The confirmation of synchronized molecular transduction in each of these systems suggests that the proposed mechanism would occur in all biochemical receptor-ligand systems.


A ligação de um ligante com um receptor molecular induz um sinal que viaja através do receptor, chegando ao domínio interno e disparando uma cascata de resposta. Em trabalhos anteriores em receptores de células T e sua ligação com antígenos estranhos, observamos a presença de padrões moleculares planares capazes de gerar campos eletromagnéticos dentro das proteínas. Esses planos mostraram um comportamento coerente (sincronizado), replicando, instantaneamente, no domínio intracelular o que ocorreu no domínio extracelular, enquanto o ligante era acoplado. No presente estudo, examinamos essa transdução – a capacidade de um sinal de acoplamento de penetrar profundamente a molécula receptora e induzir uma resposta. Verificamos a presença de um comportamento coerente em sistemas diversos de receptor-ligante. Para apreciar essa diversidade, apresentamos quatro sistemas bioquímicos diferentes: TCR-peptídeo, ADP-bomba de cálcio, hemoglobina-oxigênio e gp120-CD4 acoplamento viral. A confirmação de transdução molecular sincronizada em cada um desses sistemas sugere que o mecanismo proposto ocorreria em todos os sistemas bioquímicos receptor-ligante.


Assuntos
Peptídeos , Receptores de Superfície Celular/análise , Transdução de Sinais
16.
Braz. j. biol ; 822022.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1468657

RESUMO

Abstract The coupling of a ligand with a molecular receptor induces a signal that travels through the receptor, reaching the internal domain and triggering a response cascade. In previous work on T-cell receptors and their coupling with foreign antigens, we observed the presence of planar molecular patterns able to generate electromagnetic fields within the proteins. These planes showed a coherent (synchronized) behavior, replicating immediately in the intracellular domain that which occurred in the extracellular domain as the ligand was coupled. In the present study, we examined this molecular transduction - the capacity of the coupling signal to penetrate deep inside the receptor molecule and induce a response. We verified the presence of synchronized behavior in diverse receptor-ligand systems. To appreciate this diversity, we present four biochemically different systems - TCR-peptide, calcium pump-ADP, haemoglobin-oxygen, and gp120-CD4 viral coupling. The confirmation of synchronized molecular transduction in each of these systems suggests that the proposed mechanism would occur in all biochemical receptor-ligand systems.


Resumo A ligação de um ligante com um receptor molecular induz um sinal que viaja através do receptor, chegando ao domínio interno e disparando uma cascata de resposta. Em trabalhos anteriores em receptores de células T e sua ligação com antígenos estranhos, observamos a presença de padrões moleculares planares capazes de gerar campos eletromagnéticos dentro das proteínas. Esses planos mostraram um comportamento coerente (sincronizado), replicando, instantaneamente, no domínio intracelular o que ocorreu no domínio extracelular, enquanto o ligante era acoplado. No presente estudo, examinamos essa transdução a capacidade de um sinal de acoplamento de penetrar profundamente a molécula receptora e induzir uma resposta. Verificamos a presença de um comportamento coerente em sistemas diversos de receptor-ligante. Para apreciar essa diversidade, apresentamos quatro sistemas bioquímicos diferentes: TCR-peptídeo, ADP-bomba de cálcio, hemoglobina-oxigênio e gp120-CD4 acoplamento viral. A confirmação de transdução molecular sincronizada em cada um desses sistemas sugere que o mecanismo proposto ocorreria em todos os sistemas bioquímicos receptor-ligante.

17.
Community Dent Health ; 38(4): 226-229, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34842369

RESUMO

Initial impetus for action: Maltese Oral Health Care Professionals (OHCP) experienced changes to clinical practice and redeployment during the COVID-19 pandemic. In the early stages, there were few data on the resultant changes to the provision of dental services or their impact on the wellbeing of dental professionals. Solutions Suggested: Two questionnaires were designed to explore different domains in OHCP working on the frontline of the COVID-19 pandemic as well as in other areas/sectors. The findings were intended to inform guidance documents and to better support the profession. Findings: Anxiety-provoking factors, challenges, and areas of concern of OHCP were identified and practical recommendations to support transitioning to the 'new normal' were presented. OHCP expressed anxiety about contracting COVID-19 from their workplace and passing infection to other family members, friends, or patients. As a result, OHCP expressed the need for better protective clothing, workplace ventilation, and air filtration systems. Future implications: Provision of adequate PPE for OHCP was a priority. New guidelines for dental practice were informed by the experiences of the particpating OHCP. University modules to enhance the resilience of OHCP were among the recommendations to support practitioners.


Assuntos
COVID-19 , Pandemias , Pessoal de Saúde , Humanos , Malta/epidemiologia , Saúde Pública , SARS-CoV-2
18.
Avian Pathol ; 50(6): 490-499, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34463588

RESUMO

Md5-BAC-REV-LTR is a recombinant Marek's disease virus (MDV), with an insertion of the long terminal repeat (LTR) of reticuloendotheliosis virus (REV) into the genome of the highly virulent MDV strain rMd5. It has been shown that Md5-BAC-REV-LTR does not induce tumours and confers high protection against challenge with MDV in 15 × 7 chickens. The objective of the present study was to evaluate the protection and safety (in terms of oncogenicity and immunosuppression) of Md5-BAC-REV-LTR in commercial meat-type chickens bearing maternal antibodies against MDV. Our results show that sub-cutaneous administration of Md5-BAC-REV-LTR at 1 day of age conferred high protection (protection index PI = 84.2) against an early challenge (1 day) by contact exposure to shedder birds infected with the vv+ MDV 648A strain. In such stringent challenge conditions, Md5-BAC-REV-LTR was more protective than a commercial CVI988 (PI = 12.4) and similar to the experimental vaccine Md5-BACΔmeq (PI = 92.4). Furthermore, Md5-BAC-REV-LTR did not induce either tumours or immunosuppression in this study. Immunosuppression was evaluated by the relative lymphoid organ weights and also by the ability of the vaccine to induce late-MDV-induced immunosuppression associated with reactivation of the virus. This study shows that Md5-BAC-REV-LTR has the potential to be used as a MD vaccine and is highly protective against early challenge with vv+ MDV.RESEARCH HIGHLIGHTSMd5-BAC-REV-LTR is highly protective against early challenge with vv+ MDV in commercial meat-type chickens.Md5-BAC-REV-LTR does not cause early immunosuppression.Md5-BAC-REV-LTR does not cause late immunosuppression.Unlike other serotype 1 vaccines, Md5-BAC-REV-LTR is not detected in feather pulp at 7 days post vaccination.


Assuntos
Herpesvirus Galináceo 2 , Vacinas contra Doença de Marek , Vírus da Reticuloendoteliose , Animais , Galinhas , Terapia de Imunossupressão/veterinária , Vacinas contra Doença de Marek/genética , Carne , Sequências Repetidas Terminais/genética
19.
Talanta ; 234: 122705, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364500

RESUMO

This paper reports the preparation of the first dual electrochemical immunosensor for the simultaneous determination of the CXCL7 chemokine and the MMP3 metalloproteinase as relevant biomarkers for the better diagnosis and monitoring of rheumatoid arthritis derived from the multiple biomarkers measurement. The developed immunosensor involves the use of carboxylated magnetic beads (MBs) and dual screen-printed carbon electrodes (SPdCEs). Sandwich-type configurations implied the covalent immobilization of specific anti-CXCL7 (cAb1) or anti-MMP3 (cAb2) capture antibodies onto MBs and the use of biotinylated detection antibodies with further labelling with HRP-Strept conjugates. The resulting MBS bioconjugates were magnetically captured on the respective working electrode of the SPdCE and the determination of the antigens was accomplished by measuring the amperometric responses of H2O2 mediated by hydroquinone (HQ) at a potential value of -0.20 V. The dual immunosensor provided calibration plots with linear ranges between 1 and 75 ng mL-1 (CXCL7) (R2 = 0.997) and from 2.0 to 2000 pg mL-1 (MMP3) (R2 = 0.998) with detection limits of 0.8 ng mL-1 and 1.2 pg mL-1, respectively. The assay took 2 h 20 min for the simultaneous determination of both biomarkers. The dual immunosensor was successfully applied to the analysis of human serum from positive and negative RA patients.


Assuntos
Artrite Reumatoide , Técnicas Biossensoriais , Artrite Reumatoide/diagnóstico , Biomarcadores , Quimiocinas , Técnicas Eletroquímicas , Eletrodos , Humanos , Peróxido de Hidrogênio , Imunoensaio , Limite de Detecção , Metaloproteinase 3 da Matriz , beta-Tromboglobulina
20.
Int J Implant Dent ; 7(1): 65, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34291352

RESUMO

BACKGROUND: Zygomatic implants have been described as a therapeutic alternative for patients with severe maxillary atrophy in order to avoid bone augmentation procedures. Taking that into account, in these treatments, the key factor is the position of the implant, the virtual surgical planning (VSP) is widespread among most clinicians before surgery on the patient. However, there are no studies which evaluate the clinical relevance of these VSP. The aim of this study is to determine whether digital planning on zygomatic implants has any influence on the implant dimensions and position, even when performing conventional surgery afterwards. RESULTS: Fourteen zygomatic implants were placed in four patients. Pre-operative and post-operative helicoidal computed tomography were performed to each patient to allow the comparison between the digital planning and the final position of implants. Tridimensional deviation (TD), mesio-distal deviation (MDD), bucco-palatine deviation (BPD), and apico-coronal deviation (ACD) were evaluated as well as angular deviation (AD). Significative differences in apical TD were observed with a mean of 6.114 ± 4.28 mm (p < 0.05). Regarding implant position, only implants placed in the area of the first right molar reported significant differences (p < 0.05) for ACD. Also, implant length larger than 45 mm showed BPD significative differences (p < 0.05). CONCLUSIONS: Zygomatic implant surgery is a complex surgical procedure, and although VSP is a useful tool which helps the clinician determine the number and the length of zygomatic implants as well as its proper position, surgical experience is still mandatory.


Assuntos
Maxila , Zigoma , Atrofia/patologia , Humanos , Maxila/diagnóstico por imagem , Próteses e Implantes , Tomografia Computadorizada por Raios X , Zigoma/diagnóstico por imagem
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