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1.
Braz J Psychiatry ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33825765

RESUMO

CLINICAL TRIAL REGISTRATION: Rapid antidepressant effects associated with ketamine have shifted the landscape for the development of therapeutics to treat major depressive disorder (MDD) from a monoaminergic to glutamatergic model. Treatment with ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, may be effective, but has many non-glutamatergic targets, and clinical and logistical problems are potential challenges. These factors underscore the importance of manipulations of binding mechanics to produce antidepressant effects without concomitant clinical side effects. This will require identification of efficient biomarkers to monitor target engagement. The mismatch negativity (MMN) is a widely used electrophysiological signature linked to the activity of NMDA receptors (NMDAR) in humans and animals and validated in pre-clinical and clinical studies of ketamine. In this review, we explore the flexibility of the MMN and its capabilities for reliable use in drug development for NMDAR antagonists in MDD. We supplement this with findings from our own research with three distinct NMDAR antagonists. The research described illustrates that there are important distinctions between the mechanisms of NMDAR antagonism, which are further crystallized when considering the paradigm used to study the MMN. We conclude that the lack of standardized methodology currently prevents MMN from being ready for common use in drug discovery. This manuscript describes data collected from the following National Institutes of Health (NIH) and Veterans Affairs (VA) studies: AV-101, NCT03583554; lanicemine, NCT03166501; ketamine, NCT02556606.

2.
Top Magn Reson Imaging ; 30(2): 105-115, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33828062

RESUMO

ABSTRACT: Zero-echo time (ZTE) magnetic resonance imaging (MRI) is the newest in a family of MRI pulse sequences that involve ultrafast sequence readouts, permitting visualization of short-T2 tissues such as cortical bone. Inherent sequence properties enable rapid, high-resolution, quiet, and artifact-resistant imaging. ZTE can be performed as part of a "one-stop-shop" MRI examination for comprehensive evaluation of head and neck pathology. As a potential alternative to computed tomography for bone imaging, this approach could help reduce patient exposure to ionizing radiation and improve radiology resource utilization. Because ZTE is not yet widely used clinically, it is important to understand the technical limitations and pitfalls for diagnosis. Imaging cases are presented to demonstrate potential applications of ZTE for imaging of oral cavity, oropharynx, and jaw anatomy and pathology in adult and pediatric patients. Emerging studies indicate promise for future clinical implementation based on synthetic computed tomography image generation, 3D printing, and interventional applications.

3.
Anesth Analg ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780399

RESUMO

BACKGROUND: Patients with existing coronary artery stents are at an increased risk for major adverse cardiac events (MACEs) when undergoing noncardiac surgery (NCS). Although the use of antifibrinolytic (AF) therapy in NCS has significantly increased in the past decade, the relationship between perioperative AF use and its association with MACEs among patients with existing coronary artery stents has yet to be assessed. In this study, we aim to evaluate the association of MACEs in patients with existing coronary artery stents who receive perioperative AF therapy during orthopedic surgery. METHODS: A single-center retrospective cohort study was conducted in adult patients with existing coronary artery stents who underwent orthopedic surgery from 2008 to 2018. Two cohorts were established: patients with existing coronary artery stents who did not receive perioperative AF and patients with coronary artery stents who received perioperative AF. Associations between AF use and the primary outcome of MACEs within 30 days postoperatively and the secondary outcomes of thrombotic complications, excessive surgical bleeding, and intensive care unit (ICU) admissions were analyzed using logistic regression models. Inverse probability of treatment weighting was used to control for confounding. Secondary analyses examining the association between coronary stent type/timing and the outcomes of interest were performed using unadjusted logistic regression models. RESULTS: A total of 473 patients met study criteria, including 294 who did not receive AF and 179 patients who received AF. MACEs occurred in 15 (5.1%) patients who did not receive AF and 1 (0.6%) who received AF (P = .007). In weighted analyses, no significant difference was found in patients who received AF with regard to MACEs (odds ratio [OR] = 0.13, 95% confidence interval [CI], 0.01-1.74, P = .12), thrombotic complications (OR = 1.19, 95% CI, 0.53-2.68, P = .68), or excessive surgical bleeding (OR = 0.13, 95% CI, 0.01-2.23, P = .16) compared to patients who did not receive AF. CONCLUSIONS: The results of this study are inconclusive whether an association exists between perioperative AF use in patients with coronary artery stents and the outcome of MACEs compared to patients who did not receive perioperative AF therapy. The authors acknowledge that the imprecise CI hinders the ability to definitively determine whether an association exists in the study population. Further large prospective studies, powered to detect differences in MACEs, are needed to assess the safety of perioperative AF in patients with existing coronary artery stents and to clarify the mechanism of perioperative MACEs in this high-risk population.

4.
Biomolecules ; 11(3)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668179

RESUMO

Ocular disorders originating in the retina can result in a partial or total loss of vision, making drug delivery to the retina of vital importance. However, effectively delivering drugs to the retina remains a challenge for ophthalmologists due to various anatomical and physicochemical barriers in the eye. This review introduces diverse administration routes and the accordant pharmacokinetic profiles of ocular drugs to aid in the development of safe and efficient drug delivery systems to the retina with a focus on peptidomimetics as a growing class of retinal drugs, which have great therapeutic potential and a high degree of specificity. We also discuss the pharmacokinetic profiles of small molecule drugs due to their structural similarity to small peptidomimetics. Lastly, various formulation strategies are suggested to overcome pharmacokinetic hurdles such as solubility, retention time, enzymatic degradation, tissue targeting, and membrane permeability. This knowledge can be used to help design ocular delivery platforms for peptidomimetics, not only for the treatment of various retinal diseases, but also for the selection of potential peptidomimetic drug targets.

5.
Pediatr Radiol ; 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33772641

RESUMO

Quality in MR imaging is a comprehensive process that encompasses scanner performance, clinical processes for efficient scanning and reporting, as well as data-driven improvement involving measurement of key performance indicators. In this paper, the authors review this entire process. This article provides a framework for establishing a successful MR quality program. The collective experiences of the authors across a spectrum of pediatric hospitals is summarized here.

6.
Mayo Clin Proc ; 96(3): 619-635, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33673914

RESUMO

OBJECTIVE: To assess the association between the preoperative model for end-stage liver disease (MELD) and MELD-XI (exclude international normalized ratio) score and outcomes in patients undergoing pericardiectomy for constrictive pericarditis. PATIENTS AND METHODS: Patients >18 years of age undergoing pericardiectomy for constrictive pericarditis between January 1, 2007, and October 12, 2017, were analyzed with data for MELD and MELD-XI score calculation within 30 days preoperatively. The association between the MELD and MELD-XI scoring systems and risk of postoperative outcomes was assessed in regression models adjusting for relevant covariates. The primary outcome was operative mortality (death within 90 days or in hospital). Secondary outcomes included various measures of postoperative morbidity. RESULTS: A total of 175 and 226 patients had data for MELD/MELD-XI, respectively. Ninety-day mortality was 8.7%. When stratified into tertiles of MELD-XI, the unadjusted risk of 90-day mortality was 2.7%, 8.2%, and 16.0%, respectively. In Cox regression models fitted for MELD-XI and MELD, higher scores associated with increased risk of mortality (P<.001 for both). In secondary multivariable analyses, both MELD-XI and MELD were associated with increased incidence of renal failure and greater levels of chest-tube output and transfusion, whereas MELD-XI was additionally associated with prolonged intubation and extended intensive care unit and hospital stays. CONCLUSION: Among patients undergoing pericardiectomy for constrictive pericarditis, MELD-XI and MELD were associated with increased postoperative morbidity and mortality. Although the simpler MELD-XI score generally performed as well or better than MELD as a correlate of various outcomes, both scores can serve as a simple yet robust risk stratification tool for patients undergoing pericardiectomy for constrictive pericarditis.


Assuntos
Doença Hepática Terminal/mortalidade , Pericardiectomia/mortalidade , Pericardite Constritiva/mortalidade , Pericardite Constritiva/cirurgia , Índice de Gravidade de Doença , Adulto , Idoso , Doença Hepática Terminal/complicações , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Pericardite Constritiva/complicações , Período Pós-Operatório , Medição de Risco , Fatores de Risco , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-33707107

RESUMO

The etiologies of thrombocytopenia in patients presenting for cardiac surgery are extensive, but clinically relevant conditions generally can be categorized by those related to decreased platelet production or increased platelet destruction. Many causes require mere acknowledgment and availability of allogeneic platelet transfusion; others have unique considerations for which providers should be familiar. The purpose of this review is to provide an overview of the common causes of thrombocytopenia, summarize the literature, and discuss perioperative considerations for patients undergoing cardiac surgery.

8.
Bioorg Med Chem Lett ; 41: 127978, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33766764

RESUMO

A series of novel thiazole-containing amides were synthesized. A structure-activity relationship study of these compounds led to the identification of potent and selective PfFPPS/GGPPS inhibitors with good in vitro ADME profiles. The most promising candidate molecules were progressed to mouse in vivo PK studies and demonstrated adequate free drug exposure to warrant further investigation.

9.
Magn Reson Med ; 86(1): 69-81, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33565112

RESUMO

PURPOSE: Chemical shift-encoded MRI (CSE-MRI) is well-established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature-controlled experiments, and a multi-center, multi-vendor phantom study. THEORY AND METHODS: A technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude-, complex-, and hybrid-based CSE-MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine-site multi-vendor phantom study and compared to temperature-corrected PDFF estimation using an a priori guess for ambient room temperature. RESULTS: Simulations and temperature-controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude-based CSE-MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction. CONCLUSION: Correction for temperature reduces temperature-related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude-based CSE-MRI, even without a priori information about the temperature.

10.
Anesth Analg ; 132(4): 1101-1111, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33543869

RESUMO

BACKGROUND: Preoperative anemia is common in cardiac surgery, yet there were limited data describing the role of sex in the associations between anemia and clinical outcomes. Understanding these relationships may guide preoperative optimization efforts. METHODS: This is an observational cohort study of adults undergoing isolated coronary artery bypass grafting or single- or double-valve surgery from 2008 to 2018 at a large tertiary medical center. Multivariable regression assessed the associations between preoperative hemoglobin concentrations and a primary outcome of postoperative acute kidney injury (AKI) and secondary outcomes of perioperative red blood cell (RBC) transfusion, reoperation, vascular complications (ie, stroke, pulmonary embolism, and myocardial infarction), and hospital length of stay (LOS). Each outcome was a single regression model, using interaction terms to assess sex-specific associations between hemoglobin and outcome. RESULTS: A total of 4117 patients were included (57% men). Linear splines with sex-specific knots (13 g/dL in women and 14 g/dL in men) provided the best overall fit for preoperative hemoglobin and outcome relationships. In women, each 1 g/dL decrease in hemoglobin <13 g/dL was associated with increased odds of AKI (odds ratio = 1.49; 95% confidence interval [CI], [1.23-1.81]; P < .001), and there was no significant association between hemoglobin per 1 g/dL >13 g/dL and AKI (0.90 [0.56-1.45]; P = .67). The association between hemoglobin and AKI in men did not meet statistical significance (1.10 [0.99-1.22]; P = .076, per 1 g/dL decrease <14 g/dL; 1.00 [0.79-1.26]; P = .98 for hemoglobin per 1 g/dL >14 g/dL). In women, lower preoperative hemoglobin (per 1 g/dL decrease <13 g/dL) was associated with increased odds of RBC transfusion (2.90 [2.33-3.60]; P < .001), reoperation (1.27 [1.11-1.45]; P < .001) and a longer hospital LOS (multiplicative increase in geometric mean 1.05 [1.03-1.07]; P < .001). In men, preoperative hemoglobin (per 1 g/dL decrease <14 g/dL) was associated with increased odds of perioperative RBCs (2.56 [2.27-2.88]; P < .001) and longer hospital LOS (multiplicative increase in geometric mean 1.02 [1.01-1.04] days; P < .001) but not reoperation (0.94 [0.85-1.04]; P = .256). Preoperative hemoglobin per 1 g/dL >13 g/dL in women and 14 g/dL in men were associated with lower odds of RBCs transfusion (0.57 [0.47-0.69]; P < .001 and 0.74 [0.60-0.91]; P = .005, respectively). CONCLUSIONS: Preoperative anemia was associated with inferior clinical outcomes after cardiac surgery. The associations between hemoglobin and outcomes were distinct for women and men, with different spline knot points identified (13 and 14 g/dL, respectively). Clinicians should consider data-driven approaches to determine preoperative hemoglobin values associated with increasing risk for adverse perioperative outcomes across sexes.


Assuntos
Anemia/complicações , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Hemoglobinas/análise , Complicações Pós-Operatórias/etiologia , Idoso , Anemia/sangue , Anemia/diagnóstico , Biomarcadores/sangue , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
11.
PLoS One ; 16(2): e0246457, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33544753

RESUMO

Wild pigs (Sus scrofa) are one of the most detrimental invasive mammals in the US. Lack of adequate population control has allowed pigs to become established across the landscape, causing significant ecological and economic damage. Given the need for additional tools for reducing wild pig populations, two toxicants, warfarin and sodium nitrite, are at the forefront of the discussion regarding future wild pig management. However, no research has examined stakeholders' perspectives towards the use of toxicants in wild pig management. Given the lack of knowledge, our goal was to determine stakeholders' perspectives towards the legal use of toxicants for managing wild pigs. We surveyed 1822 individuals from three stakeholder groups (hunters, farmers, and forestland owners) across Alabama during February 2018 using an online survey following the Tailored Design Method. All three stakeholder groups were generally supportive of toxicant use, though their views differed slightly by group. Furthermore, all stakeholder groups were supportive of toxicant purchasing and use regulations, while accidental water contamination, human health impact, and incorrect usage of a toxicant were stakeholders' greatest concerns. These results indicate that these groups would likely be in support of using toxicants for wild pig management in Alabama and could be a model for other states or locations. Consequently, these results have direct implications for shaping policy and possible use of toxicants as a future wild pig management tool.

12.
Inorg Chem ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616385

RESUMO

Reactions of the pentaruthenium cluster complexes Ru5(µ5-C)(CO)15 (5), Ru5(µ5-C)(CO)14[µ-η2-O═C(NMe2)](µ-H) (6), and Ru5(µ5-C)(CO)15Cl(µ-H) (7) with ethyne (C2H2) in the presence of Me3NO yielded the zwitterionic complexes Ru5(µ5-C)(CO)13[µ-η2-CHCH(NMe3)] (8), Ru5(µ5-C)(CO)13[µ-η2-O═C(NMe2)](η1-E-CH═CH(NMe3)(µ-H) (9), and Ru5(µ5-C)(CO)13Cl[η1-E-CH═CH(NMe3)](µ-H) (11). Each product contains a positively charged trimethylammonioethenyl ligand, CH═CH(+NMe3), that is derived from a 2-trimethylammonioethenide, -CH═CH(+NMe3), zwitterion that formally has a positive charge on the nitrogen atom and a negative charge on the terminal enyl carbon atom. The trimethylammonioethenyl ligand, CH═CH(+NMe3) in 8 is a η2-ligand that bridges a Ru-Ru bond on a basal edge of the square-pyramidal Ru5 cluster by a combination of σ + π cooordination of the ethenyl group. Compounds 9 and 11 each contain a η1-terminally coordinated [η1-E-CH═CH(+NMe3)] ligand with an E stereochemistry at the C═C double bond in open Ru5 cluster complexes. Compound 9 was decarbonylated to yield the compound Ru5(µ5-C)(CO)12[µ-η2-O═C(NMe2)][µ-η2-CH═CH(NMe3)](µ-H) (10) containing a η2-bridging CHCH(+NMe3) ligand. Compound 10 was converted back to 9 by the addition of CO. Two zwitterionic products, Ru5(µ5-C)(CO)14[η1-E-CH═CH(NMe3)] (12) and Ru5(µ5-C)(CO)15[η1-E-CH═CH(NMe3)] (13), were obtained by the addition of CO to 8. Compound 12 is an intermediate en route to 13. Compound 12 contains a terminally coordinated η1-E-CH═CH(+NMe3) ligand on one of the basal Ru atoms of a square-pyramidal Ru5 cluster. Compound 13 also contains a terminally coordinated η1-E-CH═CH(+NMe3) ligand on the wing-tip bridging Ru atom of a butterfly Ru4C cluster. Treatment of 6 with methyl propiolate (HC≡CCO2Me) yielded the zwitterionic complex Ru5(µ5-C)(CO)13[µ-η2-O═C(NMe2)][η1-E-(MeO2C)C═C(H)NMe3](µ-H) (14) that is structurally similar to 9 but contains a η1-E-(MeO2C)C═C(H)(+NMe3) ligand. Compound 14 eliminated the NMe3 group to yield the compounds Ru5(µ5-C)(CO)13[µ-η2-O═C(NMe2)][µ-η2-(MeO2C)HC═CH] (15) which contains a bridging methoxycarbonyl-substituted alkenyl ligand and the known compound Ru5(µ5-C)(CO)13[µ-η2-O═C(NMe2)](HNMe2)(µ-H) (16).

13.
Parasit Vectors ; 14(1): 91, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522944

RESUMO

BACKGROUND: The Barotse floodplains of the upper Zambezi River and its tributaries are a highly dynamic environment, with seasonal flooding and transhumance presenting a shifting mosaic of potential larval habitat and human and livestock blood meals for malaria vector mosquitoes. However, limited entomological surveillance has been undertaken to characterize the vector community in these floodplains and their environs. Such information is necessary as, despite substantial deployment of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) against Anopheles vectors, malaria transmission persists across Barotseland in Zambia's Western Province. METHODS: Geographically extensive larval surveys were undertaken in two health districts along 102 km of transects, at fine spatial resolution, during a dry season and following the peak of the successive wet season. Larvae were sampled within typical Anopheles flight range of human settlements and identified through genetic sequencing of cytochrome c oxidase I and internal transcribed spacer two regions of mitochondrial and nuclear DNA. This facilitated detailed comparison of taxon-specific abundance patterns between ecological zones differentiated by hydrological controls. RESULTS: An unexpected paucity of primary vectors was revealed, with An. gambiae s.l. and An. funestus representing < 2% of 995 sequenced anophelines. Potential secondary vectors predominated in the vector community, primarily An. coustani group species and An. squamosus. While the distribution of An. gambiae s.l. in the study area was highly clustered, secondary vector species were ubiquitous across the landscape in both dry and wet seasons, with some taxon-specific relationships between abundance and ecological zones by season. CONCLUSIONS: The diversity of candidate vector species and their high relative abundance observed across diverse hydro-ecosystems indicate a highly adaptable transmission system, resilient to environmental variation and, potentially, interventions that target only part of the vector community. Larval survey results imply that residual transmission of malaria in Barotseland is being mediated predominantly by secondary vector species, whose known tendencies for crepuscular and outdoor biting renders them largely insensitive to prevalent vector control methods.

14.
Int Dent J ; 71(1): 40-52, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33616051

RESUMO

OBJECTIVE: To develop a minimum Adult Oral Health Standard Set (AOHSS) for use in clinical practice, research, advocacy and population health. MATERIALS AND METHODS: An international oral health working group (OHWG) was established, of patient advocates, researchers, clinicians and public health experts to develop an AOHSS. PubMed was searched for oral health clinical and patient-reported measures and case-mix variables related to caries and periodontal disease. The selected patient-reported outcome measures focused on general oral health, and oral health-related quality of life tools. A consensus was reached via Delphi with parallel consultation of subject matter content experts. Finally, comments and input were elicited from oral health stakeholders globally, including patients/consumers. RESULTS: The literature search yielded 1,453 results. After inclusion/exclusion criteria, 959 abstracts generated potential outcomes and case-mix variables. Delphi rounds resulted in a consensus-based selection of 80 individual items capturing 31 outcome and case-mix concepts. Global reviews generated 347 responses from 87 countries, and the patient/consumer validation survey elicited 129 responses. This AOHSS includes 25 items directed towards patients (including demographics, the impact of their oral health on oral function, a record of pain and oral hygiene practices, and financial implications of care) and items for clinicians to complete, including medical history, a record of caries and periodontal disease activity, and types of dental treatment delivered. CONCLUSION: In conclusion, utilising a robust methodology, a standardised core set of oral health outcome measures for adults, with a particular emphasis on caries and periodontal disease, was developed.


Assuntos
Saúde Bucal , Qualidade de Vida , Adulto , Consenso , Técnica Delfos , Humanos , Avaliação de Resultados em Cuidados de Saúde , Padrões de Referência
15.
J Phys Chem A ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33534579

RESUMO

Herein we probe the effects of crystalline structure and geometry on benzophenone photophysics, self-quenching, and the regenerable formation of persistent triplet radical pairs at room temperature. Radical pairs are not observed in solution but appear via an emergent pathway within the solid-state assembly. Single crystal X-ray diffraction (SC-XRD) of two sets of constitutional isomers, benzophenone bis-urea macrocycles, and methylene urea-tethered dibenzophenones are compared. Upon irradiation with 365 nm light-emitting diodes (LEDs), each forms photogenerated radicals as monitored by electron paramagnetic resonance (EPR). Once generated, the radicals exhibit half-lives from 2 to 60 days before returning to starting material without degradation. Re-exposure to light regenerates the radicals with similar efficiency. Subtle differences in the structure of the crystalline frameworks modulates the maximum concentration of photogenerated radicals, phosphorescence quantum efficiency (φ), and n-type self-quenching as observed using laser flash photolysis (LFP). These studies along with the electronic structure analysis based on the time-dependent density functional theory (TD-DFT) suggest the microenvironment surrounding benzophenone largely dictates the favorability of self-quenching or radical formation and affords insights into structure/function correlations. Advances in understanding how structure determines the excited state pathway solid-state materials undertake will aid in the design of new radical initiators, components of OLEDs, and NMR polarizing agents.

16.
Angew Chem Int Ed Engl ; 60(15): 8072-8080, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33450129

RESUMO

Acquiring fundamental knowledge of properties of actinide-based materials is a necessary step to create new possibilities for addressing the current challenges in the nuclear energy and nuclear waste sectors. In this report, we established a photophysics-electronics correlation for actinide-containing metal-organic frameworks (An-MOFs) as a function of excitation wavelength, for the first time. A stepwise approach for dynamically modulating electronic properties was applied for the first time towards actinide-based heterometallic MOFs through integration of photochromic linkers. Optical cycling, modeling of density of states near the Fermi edge, conductivity measurements, and photoisomerization kinetics were employed to shed light on the process of tailoring optoelectronic properties of An-MOFs. Furthermore, the first photochromic MOF-based field-effect transistor, in which the field-effect response could be changed through light exposure, was constructed. As a demonstration, the change in current upon light exposure was sufficient to operate a two-LED fail-safe indicator circuit.

17.
Psychopharmacology (Berl) ; 238(4): 969-978, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33404736

RESUMO

RATIONALE: Heroin intake decreases during the proestrus phase of the estrous cycle in female rats. Circulating concentrations of both estradiol and progesterone peak during proestrus, and it is not known which of these hormones, or their combination, are responsible for these effects. OBJECTIVES: The purpose of this study was to determine the effects of estradiol, progesterone, and their combination on heroin self-administration in female rats. METHODS: In Experiment 1, the estrous cycle of intact female rats was tracked daily. If a rat was in proestrus, either the estrogen receptor antagonist, raloxifene, the progesterone receptor antagonist, mifepristone, or their combination was administered 30 min prior to a heroin self-administration session. In Experiment 2, separate groups of ovariectomized female rats were treated chronically with exogenous estradiol, progesterone, estradiol + progesterone, or vehicle, and heroin intake was examined over a 100-fold dose range. RESULTS: In Experiment 1, raloxifene, but not mifepristone, significantly blocked proestrus-associated decreases in heroin intake. In Experiment 2, estrogentreated rats self-administered less heroin than any other group and significantly less heroin than rats treated with progesterone. CONCLUSIONS: These data suggest that (1) estradiol but not progesterone is responsible for proestrus-associated decreases in heroin intake and (2) estradiol decreases heroin intake relative to progesterone. These data differ from those reported previously with stimulants and suggest that estrogen-based pharmacotherapies may be of value to women with opioid use disorder.

18.
Metabolomics ; 17(2): 13, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462762

RESUMO

INTRODUCTION: Analyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples have been limited and potential demographic moderators of brain metabolism are largely unknown. OBJECTIVE: Our objective in this study was to examine sex and race differences in 33 CSF metabolites within a sample of 129 healthy individuals (37 African American women, 29 white women, 38 African American men, and 25 white men). METHODS: CSF metabolites were measured with a targeted electrochemistry-based metabolomics platform. Sex and race differences were quantified with both univariate and multivariate analyses. Type I error was controlled for by using a Bonferroni adjustment (0.05/33 = .0015). RESULTS: Multivariate Canonical Variate Analysis (CVA) of the 33 metabolites showed correct classification of sex at an average rate of 80.6% and correct classification of race at an average rate of 88.4%. Univariate analyses revealed that men had significantly higher concentrations of cysteine (p < 0.0001), uric acid (p < 0.0001), and N-acetylserotonin (p = 0.049), while women had significantly higher concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.001). African American participants had significantly higher concentrations of 3-hydroxykynurenine (p = 0.018), while white participants had significantly higher concentrations of kynurenine (p < 0.0001), indoleacetic acid (p < 0.0001), xanthine (p = 0.001), alpha-tocopherol (p = 0.007), cysteine (p = 0.029), melatonin (p = 0.036), and 7-methylxanthine (p = 0.037). After the Bonferroni adjustment, the effects for cysteine, uric acid, and 5-HIAA were still significant from the analysis of sex differences and kynurenine and indoleacetic acid were still significant from the analysis of race differences. CONCLUSION: Several of the metabolites assayed in this study have been associated with mental health disorders and neurological diseases. Our data provide some novel information regarding normal variations by sex and race in CSF metabolite levels within the tryptophan, tyrosine and purine pathways, which may help to enhance our understanding of mechanisms underlying sex and race differences and potentially prove useful in the future treatment of disease.

19.
Radiology ; 298(3): 640-651, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33464181

RESUMO

Background Proton density fat fraction (PDFF) estimated by using chemical shift-encoded (CSE) MRI is an accepted imaging biomarker of hepatic steatosis. This work aims to promote standardized use of CSE MRI to estimate PDFF. Purpose To assess the accuracy of CSE MRI methods for estimating PDFF by determining the linearity and range of bias observed in a phantom. Materials and Methods In this prospective study, a commercial phantom with 12 vials of known PDFF values were shipped across nine U.S. centers. The phantom underwent 160 independent MRI examinations on 27 1.5-T and 3.0-T systems from three vendors. Two three-dimensional CSE MRI protocols with minimal T1 bias were included: vendor and standardized. Each vendor's confounder-corrected complex or hybrid magnitude-complex based reconstruction algorithm was used to generate PDFF maps in both protocols. The Siemens reconstruction required a configuration change to correct for water-fat swaps in the phantom. The MRI PDFF values were compared with the known PDFF values by using linear regression with mixed-effects modeling. The 95% CIs were calculated for the regression slope (ie, proportional bias) and intercept (ie, constant bias) and compared with the null hypothesis (slope = 1, intercept = 0). Results Pooled regression slope for estimated PDFF values versus phantom-derived reference PDFF values was 0.97 (95% CI: 0.96, 0.98) in the biologically relevant 0%-47.5% PDFF range. The corresponding pooled intercept was -0.27% (95% CI: -0.50%, -0.05%). Across vendors, slope ranges were 0.86-1.02 (vendor protocols) and 0.97-1.0 (standardized protocol) at 1.5 T and 0.91-1.01 (vendor protocols) and 0.87-1.01 (standardized protocol) at 3.0 T. The intercept ranges (absolute PDFF percentage) were -0.65% to 0.18% (vendor protocols) and -0.69% to -0.17% (standardized protocol) at 1.5 T and -0.48% to 0.10% (vendor protocols) and -0.78% to -0.21% (standardized protocol) at 3.0 T. Conclusion Proton density fat fraction estimation derived from three-dimensional chemical shift-encoded MRI in a commercial phantom was accurate across vendors, imaging centers, and field strengths, with use of the vendors' product acquisition and reconstruction software. © RSNA, 2021 See also the editorial by Dyke in this issue.

20.
Toxicol Pathol ; : 192623320981560, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33397208

RESUMO

Many compounds affect the cellularity of hematolymphoid organs including bone marrow. Toxicologic pathologists are tasked with their evaluation as part of safety studies. An artificial intelligence (AI) tool could provide diagnostic support for the pathologist. We looked at the ability of a deep-learning AI model to evaluate whole slide images of macaque sternebrae to identify and enumerate bone marrow hematopoietic cells. The AI model was trained and able to differentiate the hematopoietic cells from the other sternebrae tissues. We compared the model to severity scores in a study with decreased hematopoietic cellularity. The mean cells/mm2 from the model was lower for each increase in severity score. The AI model was trained by 1 pathologist, providing proof of concept that AI model generation can be fast and agile, without the need of a cross disciplinary team and significant effort. We see great potential for the role of AI-based bone marrow screening.

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