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1.
Obstet Gynecol ; 135(3): 709-716, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32028490

RESUMO

OBJECTIVE: To compare the odds of a good perinatal outcome between cryopreserved and fresh donor oocytes. METHODS: We used the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System to conduct a retrospective cohort study of women undergoing donor oocyte in vitro fertilization (IVF) from 2012 to 2015. Cycles using cryopreserved embryos, a gestational carrier, or preimplantation genetic testing were excluded. The primary outcome was a good perinatal outcome, defined as a singleton live birth at 37 weeks of gestation or more with birth weight at or within 2,500 g and 4,000 g. Secondary outcomes included live birth, multiple birth, and prematurity. Generalized estimating equation models were used to test the effect of oocyte type on the primary outcome while accounting for covariates and the correlation induced by repeated cycles within a patient. RESULTS: Of the 36,925 cycles included in the analysis, 8,381 (22.7%) used cryopreserved and 28,544 (77.3%) used fresh oocytes. The odds of a good perinatal outcome were marginally but significantly lower with cryopreserved than with fresh oocytes before and after covariate adjustment (22.0% vs 24.1%, unadjusted odds ratio [OR] 0.90, 95% CI 0.85-0.96, adjusted OR 0.88, 95% CI 0.81-0.95). Compared with fresh oocytes, cryopreserved oocytes were associated with lower rates of live birth (39.6% vs 47.7%, OR 0.75, 95% CI 0.72-0.79), multiple birth (22.3% vs 31.2%, OR 0.63, 95% CI 0.58-0.69), and prematurity (27.6% vs 30.6%, OR 0.86, 95% CI 0.79-0.94). CONCLUSION: This retrospective national study demonstrated that the use of cryopreserved compared with fresh donor oocytes in IVF cycles is associated with marginally lower odds of a good perinatal outcome.

2.
Adv Mater ; : e1906722, 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31957092

RESUMO

The development of Li-S batteries is largely impeded by the growth of Li dendrites and polysulfide shuttling. To solve these two problems simultaneously, herein the study reports a "single atom array mimic" on ultrathin metal organic framework (MOF) nanosheet-based bifunctional separator for achieving the highly safe and long life Li-S batteries. In the designed separator, the periodically arranged cobalt atoms coordinated with oxygen atoms (CoO4 moieties) exposed on the surface of ultrathin MOF nanosheets, "single atom array mimic", can greatly homogenize Li ion flux through the strong Li ion adsorption with O atoms at the interface between anode and separator, leading to stable Li striping/plating. Meantime, at the cathode side, the Co single atom array mimic serves as "traps" to suppress polysulfide shuttling by Lewis acid-base interaction. As a result, the Li-S coin cells with the bifunctional separator exhibit a long cycle life with an ultralow capacity decay of 0.07% per cycle over 600 cycles. Even with a high sulfur loading of 7.8 mg cm-2 , an areal capacity of 5.0 mAh cm-2 can be remained after 200 cycles. Moreover, the assembled Li-S pouch cell displays stable cycling performance under various bending angles, demonstrating the potential for practical applications.

3.
Int Urogynecol J ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989204

RESUMO

INTRODUCTION AND HYPOTHESIS: To evaluate the risk of post-injection urinary tract infection (UTI) after onabotulinumtoxin A (BTX-A) treatment based on the timing of when antibiotic prophylaxis is started. METHODS: This is a retrospective cohort study of 111 women with refractory idiopathic overactive bladder who underwent intradetrusor injection of BTX-A. Two cohorts were identified: (1) 67 women who started antibiotic prophylaxis with ciprofloxacin 1 day prior to injection; (2) 44 women who received antibiotic prophylaxis with ciprofloxacin after injection only. We assessed for post-injection UTI within 90 days after BTX-A. Multivariable logistic regression was performed to adjust for potential confounders. RESULTS: One hundred eleven women underwent BTX-A. In total, 30 (27%) had a UTI within 90 days; these included 15/67 (22%) of those who started antibiotics 1 day prior to injection and 15/44 (34%) of those receiving antibiotics after injection. While the unadjusted analysis showed no significant associations between timing of antibiotic administration and UTI (OR = 0.56; 95% CI = 0.24, 1.30; p = 0.18), an adjusted analysis showed the pre-procedure antibiotic group had a significant reduction in post-procedure UTI after controlling for age, history of UTI, diabetes, and urinary retention requiring catheterization (OR = 0.23; 95% CI = 0.07, 0.73; p = 0.01). CONCLUSIONS: Starting antibiotics 1 day prior to BTX-A injection decreases the odds of post-injection UTI compared with women who use post-procedure antibiotic prophylaxis over shorter duration. Consideration should be given to beginning antibiotic prophylaxis prior to the procedure and continuing it for 4 total days to decrease the risk of UTI.

4.
J Clin Anesth ; 61: 109626, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31699495

RESUMO

STUDY OBJECTIVE: The lag in creatinine-mediated diagnosis of cardiac surgery-associated acute kidney injury (AKI) may be impeding the development of renoprotection therapies. Postoperative renal resistive index (RRI) measured by transabdominal Doppler ultrasound is a promising early AKI biomarker. RRI measured intraoperatively by transesophageal echocardiography (TEE) is available even earlier but is less evaluated. Therefore, we conducted an assessment of intraoperative RRI as an AKI biomarker using previously reported post-renal insult thresholds. DESIGN: Retrospective convenience sample. SETTING: Intraoperative. PATIENTS: 180 adult cardiac surgical patients between July 2013 and July 2014. INTERVENTION: None. MEASUREMENTS: Pre- and post-cardiopulmonary bypass (CPB) RRI thresholds, measured using intraoperative TEE, exceeding 0.74 or 0.79 were used to evaluate for an association with KDIGO AKI risk using the Chi-square test. Other consensus AKI criteria (AKIN, RIFLE) were similarly evaluated. Additional t-test analyses examined the relationship of pre- and pre-to-post (delta) CPB RRI with AKI. MAIN RESULTS: Post-CPB RRI for 99 patients included 36 and 23 with values exceeding 0.74 and 0.79, respectively. Analyses confirmed associations of both RRI thresholds with all consensus AKI definitions (0.74; KDIGO: p = 0.05, AKIN: p = 0.03, RIFLE: p = 0.03, 0.79; KDIGO: p = 0.002, AKIN: p = 0.001, RIFLE: p = 0.004). In contrast, pre-CPB and pre-to post-CPB RRI were not associated with AKI. CONCLUSIONS: RRI obtained intraoperatively in cardiac surgery patients, assessed using previously reported thresholds, is highly associated with AKI and warrants further evaluation as a promising "earliest" AKI biomarker. These significant findings suggest that RRI assessment should be included in the standard intraoperative TEE exam.

5.
Adv Mater ; 32(7): e1904249, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31880031

RESUMO

The development of highly efficient photocatalytic systems with rapid photogenerated charge separation and high surface catalytic activity is highly desirable for the storage and conversion of solar energy, yet remains a grand challenge. Herein, a conceptionally new form of atomically dispersed Co-P3 species on CdS nanorods (CoPSA-CdS) is designed and synthesized for achieving unprecedented photocatalytic activity for the dehydrogenation of formic acid (FA) to hydrogen. X-ray absorption near edge structure, X-ray photoelectron spectroscopy, and time-resolved photoluminescence results confirm that the Co-P3 species have a unique electron-rich feature, greatly improving the efficiency of photogenerated charge separation through an interface charge effect. The in situ attenuated total reflection infrared spectra reveal that the Co-P3 species can achieve much better dissociation adsorption of FA and activation of CH bonds than traditional sulfur-coordinated Co single atom-loaded CdS nanorods (CoSSA-CdS). These two new features make CoPSA-CdS exhibit the unprecedented 50-fold higher activity in the photocatalytic dehydrogenation of FA than CoSSA-CdS, and also much better activity than the Ru-, Rh-, Pd-, or Pt-loaded CdS. Besides, CoPSA-CdS also shows the highest mass activity (34309 mmol gCo -1 h-1 ) of Co reported to date. First-principles simulation reveals that the Co-P3 species herein can form an active PHCOO intermediate for enhancing the rate-determining dissociation adsorption of FA.

6.
J Pediatr Orthop ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31368922

RESUMO

BACKGROUND: Supracondylar humerus (SCH) fractures are common elbow injuries in pediatric patients. The American Academy of Orthopedic Surgeons published guidelines for the standard of care in the treatment of displaced SCH fractures, however, no recommendations for follow-up care were made. With the recent push to eliminate unnecessary radiographs and decrease health care costs, many are questioning postoperative protocols. The purpose of our study was to evaluate the utility of the 1-week follow-up appointment after closed reduction and percutaneous pinning (CRPP) of displaced SCH fractures. METHODS: A retrospective review performed at a single institution from 2014 to 2016 included patients under 14 years of age with a closed, displaced SCH fracture treated with CRPP. Exclusion criteria included patients without complete clinical or radiographic follow-up. Variables examined included time to initial follow-up, change in treatment plan after 1-week x-rays, complications, demographics, fracture type, pin number and configuration, reduction parameters, immobilization, time to pin removal, duration of casting, and clinical outcome. RESULTS: A total of 412 patients were divided into 2 groups based on time to initial follow-up. Overall, 368 had an initial follow-up at 7 to 10 days (group 1) and 44 at 21 to 28 days (group 2). There was no difference in age, sex, fracture type, pin configuration, or a number of pins between groups. Statistically significant findings included time to initial follow-up and days to pin removal (group 1 at 26.2 d vs. group 2 at 23.8 d), type of immobilization (group 1 with 5% circumferential casts and group 2 with 70%), and time to surgery (26.2 vs. 62.9 h, respectively). There was no significant difference in complication rates and only a 0.5% rate of change in management in group 1. CONCLUSIONS: Early postoperative follow-up and radiographs did not change the patient outcome and might be eliminated in children with displaced SCH fractures treated with CRPP. Given the current focus of on efficiency and cost-effective care, eliminating the 1-week postoperative appointment would improve appointment availability and decrease medical cost. LEVEL OF EVIDENCE: Level III-Therapeutic.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31295185

RESUMO

OBJECTIVES: The objective of this study was to evaluate the risk of postprocedure urinary tract infection (UTI) after injection of onabotulinum toxin A (BTX-A) in women who had a UTI within 30 days before procedure. METHODS: This was a retrospective cohort study of women who underwent their first injection of BTX-A from 2010 to 2016. Two cohorts were identified: (1) recent UTI (within 30 days before injection) and (2) no recent UTI. Our primary outcome was UTI within 90 days after BTX-A. Continuous variables were analyzed using the Wilcoxon rank sum test, and categorical variables were analyzed using Fisher exact or χ tests. RESULTS: One hundred sixty-six women underwent their first BTX-A injection. Twenty-five (15%) had a recent UTI and 141 (85%) did not. Women with a recent UTI were more likely to have a subsequent infection (52% vs 26%, P < 0.01). However, in a logistic regression model, controlling for history of recurrent UTI, age, history of diabetes mellitus, periprocedural antibiotics, and urinary retention requiring catheterization, the association between having a recent UTI, and a subsequent UTI was no longer significant (adjusted odds ratio, 1.98; 95% confidence interval, 0.60-6.50; P = 0.26). CONCLUSIONS: Performing a first injection of BTX-A within 30 days of a UTI does not increase the odds of postprocedure UTI. Therefore, BTX-A therapy does not need to be delayed after a recent UTI.

8.
Arthritis Res Ther ; 21(1): 146, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196179

RESUMO

BACKGROUND: To identify a synovial fluid (SF) biomarker profile characteristic of individuals with an inflammatory osteoarthritis (OA) endotype. METHODS: A total of 48 knees (of 25 participants) were characterized for an extensive array of SF biomarkers quantified by Rules Based Medicine using the high-sensitivity multiplex immunoassay, Myriad Human InflammationMAP® 1.0, which included 47 different cytokines, chemokines, and growth factors related to inflammation. Multivariable regression with generalized estimating equations (GEE) and false discovery rate (FDR) correction was used to assess associations of SF RBM biomarkers with etarfolatide imaging scores reflecting synovial inflammation; radiographic knee OA severity (based on Kellgren-Lawrence (KL) grade, joint space narrowing, and osteophyte scores); knee joint symptoms; and SF biomarkers associated with activated macrophages and knee OA progression including CD14 and CD163 (shed by activated macrophages) and elastase (shed by activated neutrophils). RESULTS: Significant associations of SF biomarkers meeting FDR < 0.05 included soluble (s)VCAM-1 and MMP-3 with synovial inflammation (FDR-adjusted p = 0.025 and 1.06 × 10-7); sVCAM-1, sICAM-1, TIMP-1, and VEGF with radiographic OA severity (p = 1.85 × 10-5 to 3.97 × 10-4); and VEGF, MMP-3, TIMP-1, sICAM-1, sVCAM-1, and MCP-1 with OA symptoms (p = 2.72 × 10-5 to 0.050). All these SF biomarkers were highly correlated with macrophage markers CD163 and CD14 in SF (r = 0.43 to 0.90, FDR < 0.05); all but MCP-1 were also highly correlated with neutrophil elastase in SF (r = 0.62 to 0.89, FDR < 0.05). CONCLUSIONS: A subset of six SF biomarkers was related to synovial inflammation in OA, as well as radiographic and symptom severity. These six OA-related SF biomarkers were specifically linked to indicators of activated macrophages and neutrophils. These results attest to an inflammatory OA endotype that may serve as the basis for therapeutic targeting of a subset of individuals at high risk for knee OA progression. TRIAL REGISTRATION: Written informed consent was received from participants prior to inclusion in the study; the study was registered at ClinicalTrials.gov ( NCT01237405 ) on November 9, 2010, prior to enrollment of the first participant.

9.
Vox Sang ; 114(4): 374-385, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30937927

RESUMO

BACKGROUND/OBJECTIVES: Prothrombin complex concentrates (PCC) are increasingly administered off-label in the United States to treat bleeding in cardiovascular surgical patients and carry the potential risk for acquired thromboembolic side-effects after surgery. Therefore, we hypothesized that the use of low-dose 3-factor (3F) PCC (20-30 IU/kg), as part of a transfusion algorithm, reduces bleeding without increasing postoperative thrombotic/thromboembolic complications. MATERIALS/METHODS: After IRB approval, we retrospectively analysed 114 consecutive, complex cardiovascular surgical patients (age > 18 years), between February 2014 and June 2015, that received low-dose 3F-PCC (Profilnine® ), of which seven patients met established exclusion criteria. PCC was dosed according to an institutional perioperative algorithm. Allogeneic transfusions were recorded before and after PCC administration (n = 107). The incidence of postoperative thromboembolic events was determined within 30 days of surgery, and Factor II levels were measured in a subset of patients (n = 20) as a quality control measure to avoid excessive PCC dosing. RESULTS: Total allogeneic blood product transfusion reached a mean of 12·4 ± 9·9 units before PCC and 5·0 ± 6·3 units after PCC administration (P < 0·001). The mean PCC dose was 15·8 ± 7·1 IU/kg. Four patients (3·8%) each experienced an ischaemic stroke on postoperative day 1, 2, 4 and 27. Seven patients (6·5%) had acquired venous thromboembolic disease within 10 days of surgery. Median factor II level after transfusion algorithm adherence and PCC administration was 87%. CONCLUSIONS: 3F-PCC use for refractory bleeding after cardiovascular surgery resulted in reduced transfusion of allogeneic blood and blood products. Adherence to this algorithmic approach was associated with an acceptable incidence of postoperative thrombotic/thromboembolic complications.


Assuntos
Fatores de Coagulação Sanguínea/química , Coagulação Sanguínea , Hemorragia/terapia , Hemostasia , Tromboembolia/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Testes de Coagulação Sanguínea , Plaquetas/citologia , Transfusão de Sangue , Ponte Cardiopulmonar , Feminino , Fibrinogênio/química , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
10.
Basic Res Cardiol ; 114(3): 20, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30900023

RESUMO

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor beta 1 (TGF-ß1) superfamily that reverses age-related cardiac hypertrophy, improves muscle regeneration and angiogenesis, and maintains progenitor cells in injured tissue. Recently, targeted myocardial delivery of the GDF11 gene in aged mice was found to reduce heart failure and enhance the proliferation of cardiac progenitor cells after myocardial ischemia-reperfusion (I-R). No investigations have as yet explored the cardioprotective effect of exogenous recombinant GDF11 in acute I-R injury, despite the convenience of its clinical application. We sought to determine whether exogenous recombinant GDF11 protects against acute myocardial I-R injury and investigate the underlying mechanism in Sprague-Dawley rats. We found that GDF11 reduced arrhythmia severity and successfully attenuated myocardial infarction; GDF11 also increased cardiac function after I-R, enhanced HO-1 expression and decreased oxidative damage. GDF11 activated the canonical TGF-ß signaling pathway and inactivated the non-canonical pathways, ERK and JNK signaling pathways. Moreover, administration of GDF11 prior to reperfusion protected the heart from reperfusion damage. Notably, pretreatment with the activin-binding protein, follistatin (FST), inhibited the cardioprotective effects of GDF11 by blocking its activation of Smad2/3 signaling and its inactivation of detrimental TGF-ß signaling. Our data suggest that exogenous GDF11 has cardioprotective effects and may have morphologic and functional recovery in the early stage of myocardial I-R injury. GDF11 may be an innovative therapeutic approach for reducing myocardial I-R injury.


Assuntos
Fatores de Diferenciação de Crescimento/uso terapêutico , Coração/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fator de Crescimento Transformador beta/metabolismo , Animais , Apoptose/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Proteína Forkhead Box O3/metabolismo , Fatores de Diferenciação de Crescimento/farmacologia , Heme Oxigenase (Desciclizante)/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Proteínas Smad Reguladas por Receptor/metabolismo
11.
Environ Sci Technol ; 53(5): 2705-2712, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30726066

RESUMO

Organic contaminants in water have become one of the most serious environmental problems worldwide. Adsorption is one of the most promising approaches to remove organic pollutants from water. However, the existing adsorbents have relatively low removal efficiency, complex preparation processes, and high cost, which limit their practical applications. Here, we developed three-dimensional (3D) zirconium metal-organic frameworks (MOFs) encapsulated in a natural wood membrane (UiO-66/wood membrane) for highly efficient organic pollutant removal from water. UiO-66 MOFs were in situ grown in the 3D low-tortuosity wood lumens by a facile solvothermal strategy. The resulting UiO-66/wood membrane contains the highly mesoporous UiO-66 MOF structure as well as many elongated and open lumens along the direction of the wood growth. Such a unique structural feature improves the mass transfer of organic pollutants and increases the contact probability of organic contaminants with UiO-66 MOFs as the water flows through the membrane, thereby improving the removal efficiency. Furthermore, the integrated multilayer filter consisting of three pieces of UiO-66/wood membranes exhibits a high removal efficiency (96.0%) for organic pollutants such as rhodamine 6G, propranolol, and bisphenol A at the flux of 1.0 × 103 L·m-2·h-1. The adsorbed capacity of UiO-66/wood for Rh6G (based on the content of UiO-66 MOFs) is calculated to be 690 mg·g-1. We believe that such low-cost and scalable production of the UiO-66/wood membrane has broad applications for wastewater treatment and other related pollutant removal.


Assuntos
Poluentes Ambientais , Estruturas Metalorgânicas , Poluentes Químicos da Água , Adsorção , Madeira
12.
ACS Appl Mater Interfaces ; 11(6): 6009-6014, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30644717

RESUMO

Nanowires have a wide range of applications, such as transparent electrodes, Li-ion battery anodes, light-emitting diodes, solar cells, and electronic devices. Currently, aluminum (Al) nanowires can be synthesized by thermally induced substitution of germanium (Ge) nanowires, chemical vapor deposition on other metal substrates, and template-assisted growth methods. However, there are still challenges in fabricating extremely high-purity nanowires, large-scale manufacturing, and simplifying the synthesis process and conditions. Here, we report for the first time that single-crystal Al nanowires can be one-step, in situ synthesized on a reduced graphene oxide (RGO) substrate on a large scale without using any catalysts. Through a simple high temperature treatment process, commercial micro-sized Al powders in RGO film were transformed into a single-crystal Al nanowire with an average length of 1.2 µm and an average diameter of 18 nm. The possible formation mechanism of the single-crystal Al nanowires is proposed as follows: hot aluminum atoms eject from the pristine aluminum/alumina core/shell structure of Al powders when they build up enough energy from the thermal stress under high temperature and confined space conditions, which is supported by both experimental and computational results. The method introduced here can be extended to allow the synthesis of one-dimensional highly reactive materials, like alkali metal nanowires, in confined spaces.

13.
PLoS One ; 14(1): e0210870, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30682063

RESUMO

We propose a set of family-based burden and kernel tests for censored traits (FamBAC and FamKAC). Here, censored traits refer to time-to-event outcomes, for instance, age-at-onset of a disease. To model censored traits in family-based designs, we used the frailty model, which incorporated not only fixed genetic effects of rare variants in a region of interest but also random polygenic effects shared within families. We first partitioned genotype scores of rare variants into orthogonal between- and within-family components, and then derived their corresponding efficient score statistics from the frailty model. Finally, FamBAC and FamKAC were constructed by aggregating the weighted efficient scores of the within-family components across rare variants and subjects. FamBAC collapsed rare variants within subject first to form a burden test that followed a chi-squared distribution; whereas FamKAC was a variant component test following a mixture of chi-squared distributions. For FamKAC, p-values can be computed by permutation tests or for computational efficiency by approximation methods. Through simulation studies, we showed that type I error was correctly controlled by FamBAC for various variant weighting schemes (0.0371 to 0.0527). However, FamKAC type I error rates based on approximation methods were deflated (max 0.0376) but improved by permutation tests. Our simulations also demonstrated that burden test FamBAC had higher power than kernel test FamKAC when high proportion (e.g. ≥ 80%) of causal variants had effects in the same direction. In contrast, when the effects of causal variants on the censored trait were in mixed directions, FamKAC outperformed FamBAC and had comparable or higher power than an existing method, RVFam. Our proposed framework has the flexibility to accommodate general nuclear families, and can be used to analyze sequence data for censored traits such as age-at-onset of a complex disease of interest.


Assuntos
Família , Estudos de Associação Genética/métodos , Variação Genética , Modelos Genéticos , Idade de Início , Simulação por Computador , Feminino , Frequência do Gene , Estudos de Associação Genética/estatística & dados numéricos , Genótipo , Humanos , Masculino , Modelos de Riscos Proporcionais
14.
ACS Nano ; 13(2): 2167-2175, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30689350

RESUMO

Despite its very high capacity (4200 mAh g-1), the widespread application of the silicon anode is still hampered by severe volume changes (up to 300%) during cycling, which results in electrical contact loss and thus dramatic capacity fading with poor cycle life. To address this challenge, 3D advanced Mxene/Si-based superstructures including MXene matrix, silicon, SiO x layer, and nitrogen-doped carbon (MXene/Si@SiO x@C) in a layer-by-layer manner were rationally designed and fabricated for boosting lithium-ion batteries (LIBs). The MXene/Si@SiO x@C anode takes the advantages of high Li+ ion capacity offered by Si, mechanical stability by the synergistic effect of SiO x, MXene, and N-doped carbon coating, and excellent structural stability by forming a strong Ti-N bond among the layers. Such an interesting superstructure boosts the lithium storage performance (390 mAh g-1 with 99.9% Coulombic efficiency and 76.4% capacity retention after 1000 cycles at 10 C) and effectively suppresses electrode swelling only to 12% with no noticeable fracture or pulverization after long-term cycling. Furthermore, a soft package full LIB with MXene/Si@SiO x@C anode and Li[Ni0.6Co0.2Mn0.2]O2 (NCM622) cathode was demonstrated, which delivers a stable capacity of 171 mAh g-1 at 0.2 C, a promising energy density of 485 Wh kg-1 based on positive active material, as well as good cycling stability for 200 cycles even after bending. The present MXene/Si@SiO x@C becomes among the best Si-based anode materials for LIBs.

15.
Transl Stroke Res ; 10(2): 231-239, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29756167

RESUMO

Sex dimorphism has been demonstrated after experimental intracerebral hemorrhage (ICH). Decreased mortality and improved neurobehavioral outcomes occur in female compared to male mice after intrastriatal autologous blood or collagenase injection. Sex-specific differences in post-ICH gene and protein expression may provide mechanistic insight into this phenomenon. Ten- to 12-week-old C57BL/6 male (M) and female in high estrous state (HE-F) underwent left intrastriatal collagenase injection. We assessed neurobehavioral outcomes over the first 30 days, hematoma volume and cerebral edema evolution over the first 24 h, and transcriptomic gene and protein expression at pre-selected time points during the acute phase of injury. Genome-wide expression profiling was performed with Affymetrix GeneChip Mouse Genome 2.0 Probes, and proteomics analyses were performed using mass spectroscopy. Sex does not affect hemorrhage evolution, but female sex is associated with improved neurobehavioral recovery after ICH. A total of 7037 probes qualified for our filtering criteria, representing 5382 mapped genes and 256 unmapped genes. Female-unique pathways involved cell development, growth, and proliferation, while male-unique pathways involved molecular degradation. At 6 and 24 h post-ICH, differential expression was observed in 850 proteins vs baseline in males, 608 proteins vs baseline in females, and 1 protein in females vs males. Female sex is associated with improved neurobehavioral recovery, and differential gene and protein expression after intrastriatal collagenase injection.


Assuntos
Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Regulação da Expressão Gênica/fisiologia , Caracteres Sexuais , Animais , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/fisiopatologia , Modelos Animais de Doenças , Feminino , Imagem por Ressonância Magnética , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora , Proteômica , RNA Mensageiro/metabolismo , Transdução de Sinais/fisiologia , Fatores de Tempo
16.
Circ Genom Precis Med ; 11(9): e002228, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30354330

RESUMO

BACKGROUND: Outcomes of tailoring statin-type based on solute carrier organic anion transporterfamily member 1B1 ( SLCO1B1)pharmacogenetic toxicity information on patient, provider, and pharmacological outcomes are unknown. METHODS: The trial randomized 159 patients not taking statins because of prior statin myalgia 1:1 to receiving SLCO1B1 GIST (Genotype Informed Statin Therapy) versus usual care (UC) and followed for up to 8 months. The UC arm received their SLCO1B1 results post-trial. The primary outcome was statin adherence using the Morisky Medication Adherence Scale, which was assessed in those patients who reinitiated statins. Secondary outcomes assessed in all participants included statin reinitiation and LDLc (low-density lipoprotein cholesterol), within and post-trial. Using commercial laboratory data, serial LDLc were compared between 1907 patients receiving SLCO1B1 testing and propensity-matched, untested controls. RESULTS: Trial participants were 25% SLCO1B1*5 carriers. Statin adherence was similar between arms (Morisky Medication Adherence Scale in GIST versus UC, 6.8±1.5 versus 6.9±1.6, P=0.96). GIST led to more new statin prescriptions (55.4% versus 38.0%, P=0.04) and lower LDLc at 3 months (131.9±42.0 versus 144.4±43.0 mg/dL; P=0.048) with similar magnitude at 8 months (128.6±37.9 versus 141.0±44.4; P=0.12). SLCO1B1*5 carriers exhibited a greater drop in LDLc with GIST versus UC (interaction P=0.048). Post-trial, LDLc decreased in UC participants who crossed over to GIST compared with those allocated to GIST (-14.9±37.8 versus +9.0±37.3 mg/dL, P=0.03). Patients tested for SLCO1B1 though a commercial laboratory had a greater LDLc decrease ( P=0.04) compared with controls. CONCLUSIONS: Delivery of SLCO1B1 pharmacogenetic testing that addresses statin myalgia improved statin reinitiation and LDLc but did not improve self-reported statin adherence. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01894230.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Testes Farmacogenômicos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , LDL-Colesterol/sangue , Feminino , Genótipo , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , /estatística & dados numéricos , Medicina de Precisão/métodos , Adulto Jovem
17.
Thromb Haemost ; 118(9): 1572-1585, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30103242

RESUMO

INTRODUCTION: Thrombocytopenia after cardiac surgery independently predicts stroke, acute kidney injury and death. To understand the underlying risks and mechanisms, we analysed genetic variations associated with thrombocytopenia in patients undergoing coronary artery bypass grafting (CABG) surgery. MATERIALS AND METHODS: Study subjects underwent isolated on-pump CABG surgery at Duke University Medical Center. Post-operative thrombocytopenia was defined as platelet count < 100 × 109/L. Using a logistic regression model adjusted for clinical risk factors, we performed a genome-wide association study in a discovery cohort (n = 860) and validated significant findings in a replication cohort (n = 296). Protein expression was assessed in isolated platelets by immunoblot. RESULTS: A total of 63 single-nucleotide polymorphisms met a priori discovery thresholds for replication, but only 1 (rs9574547) in the intergenic region upstream of sprouty 2 (SPRY2) met nominal significance in the replication cohort. The minor allele of rs9574547 was associated with a lower risk for thrombocytopenia (discovery cohort, odds ratio, 0.45, 95% confidence interval, 0.30-0.67, p = 9.76 × 10-5) with the overall association confirmed by meta-analysis (meta-p = 7.88 × 10-6). Immunoblotting demonstrated expression of SPRY2 and its dynamic regulation during platelet activation. Treatment with a functional SPRY2 peptide blunted platelet extracellular signal-regulated kinase (ERK) phosphorylation after agonist stimulation. CONCLUSION: We identified the association of a genetic polymorphism in the intergenic region of SPRY2 with a decreased incidence of thrombocytopenia after CABG surgery. Because SPRY2-an endogenous receptor tyrosine kinase inhibitor-is present in platelets and modulates essential signalling pathways, these findings support a role for SPRY2 as a novel modulator of platelet responses after cardiac surgery.


Assuntos
Plaquetas/fisiologia , Ponte de Artéria Coronária , Genótipo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Complicações Pós-Operatórias/genética , Trombocitopenia/genética , Idoso , Células Cultivadas , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Transdução de Sinais/genética , Trombocitopenia/etiologia
18.
Am Stat ; 72(2): 199-205, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30122786

RESUMO

The score statistic continues to be a fundamental tool for statistical inference. In the analysis of data from high-throughput genomic assays, inference on the basis of the score usually enjoys greater stability, considerably higher computational efficiency, and lends itself more readily to the use of resampling methods than the asymptotically equivalent Wald or likelihood ratio tests. The score function often depends on a set of unknown nuisance parameters which have to be replaced by estimators, but can be improved by calculating the efficient score, which accounts for the variability induced by estimating these parameters. Manual derivation of the efficient score is tedious and error-prone, so we illustrate using computer algebra to facilitate this derivation. We demonstrate this process within the context of a standard example from genetic association analyses, though the techniques shown here could be applied to any derivation, and have a place in the toolbox of any modern statistician. We further show how the resulting symbolic expressions can be readily ported to compiled languages, to develop fast numerical algorithms for high-throughput genomic analysis. We conclude by considering extensions of this approach. The code featured in this report is available online as part of the supplementary material.

19.
ACS Appl Mater Interfaces ; 10(28): 23834-23841, 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-29956918

RESUMO

High-performance flexible energy storage devices are an important prerequisite to the utilization of various advanced wearable electronics, such as healthcare sensors and smart textiles. In this work, we design a wearable all-solid-state, all-in-one asymmetric supercapacitor by integrating current collectors, a separator, and negative and positive electrodes into a thin, flexible, and porous polyamide nanofiber film. The positive and negative electrodes are, respectively, electrodeposited onto each side of the carbon nanotube-modified porous polyamide nanofiber film to form the integrated and compact asymmetric cell. The all-in-one thin-film asymmetric supercapacitor is binder-, additive-, and metal current collector-free, which can effectively decrease the cost, simplify the assembly procedures, and increase the energy density. The assembled flexible all-in-one asymmetric supercapacitor with a compact structure shows high gravimetric and volumetric specific capacitances of 70 F g-1 and 3.1 F cm-3 under a current density of 0.5 A g-1 in a neutral polyvinyl alcohol/LiCl gel electrolyte, respectively. Additionally, the all-in-one asymmetric cell displays a favorable volumetric energy density of 1.1 W h L-3, which is among the highest compared with other reported flexible solid-state supercapacitors. Notably, multiple cell units can be integrated in one piece of polyamide nanofiber film and connected in series to satisfy the need of high output voltage.

20.
Nano Lett ; 18(6): 3926-3933, 2018 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-29787678

RESUMO

Solid-state electrolytes (SSEs) have been widely considered as enabling materials for the practical application of lithium metal anodes. However, many problems inhibit the widespread application of solid state batteries, including the growth of lithium dendrites, high interfacial resistance, and the inability to operate at high current density. In this study, we report a three-dimensional (3D) mixed electron/ion conducting framework (3D-MCF) based on a porous-dense-porous trilayer garnet electrolyte structure created via tape casting to facilitate the use of a 3D solid state lithium metal anode. The 3D-MCF was achieved by a conformal coating of carbon nanotubes (CNTs) on the porous garnet structure, creating a composite mixed electron/ion conductor that acts as a 3D host for the lithium metal. The lithium metal was introduced into the 3D-MCF via slow electrochemical deposition, forming a 3D lithium metal anode. The slow lithiation leads to improved contact between the lithium metal anode and garnet electrolyte, resulting in a low resistance of 25 Ω cm2. Additionally, due to the continuous CNT coating and its seamless contact with the garnet we observed highly uniform lithium deposition behavior in the porous garnet structure. With the same local current density, the high surface area of the porous garnet framework leads to a higher overall areal current density for stable lithium deposition. An elevated current density of 1 mA/cm2 based on the geometric area of the cell was demonstrated for continuous lithium cycling in symmetric lithium cells. For battery operation of the trilayer structure, the lithium can be cycled between the 3D-MCF on one side and the cathode infused into the porous structure on the opposite side. The 3D-MCF created by the porous garnet structure and conformal CNT coating provides a promising direction toward new designs in solid-state lithium metal batteries.

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