Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 504
Filtrar
1.
Acad Med ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33656008

RESUMO

PURPOSE: Socioeconomic and geographic determinants of medical school application and matriculation may help explain the unequal distribution of physicians in the United States. This study describes trends in MD-granting medical school application and matriculation rates and explores the relationship between county median family income, proximity to a medical school, and medical school application and matriculation rates. METHOD: Data were obtained from the Association of American Medical Colleges, including the age, gender, and Federal Information Processing Standards code for county of legal residence for each applicant and matriculant to MD-granting medical schools in the United States from 2001 through 2015. The application and matriculation rates in each county were calculated using the number of applicants and matriculants per 100,000 residents. Counties were classified into 4 groups according to the county median family income (high-income, middle-income, middle-low-income, low-income). The authors performed Chi-square tests to assess trends across the study period and the association of county median family income with application and matriculation rates. RESULTS: There were 581,833 applicants and 262,730 (45.2%) matriculants to MD-granting medical schools between 2001 and 2015. The application rate per 100,000 residents during 2001-2005, 2006-2010, and 2011-2015 was 57.2, 62.7, and 69.0, respectively, and the corresponding matriculation rate was 27.5, 28.1, and 29.8, respectively. The ratio of the application rate in high-income counties to that in low-income counties during the 3 time periods was 1.9, 2.4, and 2.8, respectively. CONCLUSIONS: The application and matriculation rates to MD-granting medical schools increased steadily from 2001 to 2015. Yet, applicants and matriculants disproportionately came from high-income counties. The differences in the application and matriculation rates between low-income and high-income counties grew during this period. Exploring these differences can lead to better understanding of the factors that drive geographic differences in physician access and the associated health disparities across the United States.

2.
J Integr Med ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33547011

RESUMO

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has become an increasingly severe public health emergency. Although traditional Chinese medicine (TCM) has helped to combat COVID-19, public perception of TCM remains controversial. We used the theory of planned behavior (TPB) to identify factors that affect the intention to use TCM. METHODS: A cross-sectional web-based survey of 10,824 individuals from the general public was conducted between March 16 and April 2, 2020. The participants were recruited using a snowball sampling method. Data were collected using a self-administered questionnaire, based on the TPB. The questionnaire consisted of demographic characteristics and TPB structures. Structural equation modeling was used to identify predictors of intention. RESULTS: The results indicated the model explained 77.5% and 71.9% of intention and attitude variance. Intention to use TCM had the strongest relationship with attitude (P < 0.001), followed by past behavior (P < 0.001), subjective norms (P < 0.001) and perceived behavioral control (P < 0.001). Attitudes toward TCM were significantly affected by perceived behavioral control (P < 0.001), subjective norms (P < 0.001) and cognition of TCM (P < 0.001). CONCLUSION: Attitude is a key factor in determining the intention to use TCM, followed by past behaviors, subjective norms and perceived behavioral control. Our results offer important implications for health policy makers to promote the use of TCM.

3.
Adipocyte ; 10(1): 48-65, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33403891

RESUMO

Mammalian adipose tissue can be divided into two major types, namely, white adipose tissue (WAT) and brown adipose tissue (BAT). According to classical view, the main function of WAT is to store excess energy in the form of triglycerides, while BAT is a thermogenic tissue that acts a pivotal part in maintaining the core body temperature. White adipocytes display high plasticity and can transdifferentiate into beige adipocytes which have many similar morphological and functional properties with brown adipocytes under the stimulations of exercise, cold exposure and other factors. This phenomenon is also known as 'browning of WAT'. In addition to transdifferentiation, beige adipocytes can also come from de novo differentiation from tissue-resident progenitors. Activating BAT and inducing browning of WAT can accelerate the intake of glycolipids and reduce the insulin secretion requirement, which may be a new strategy to improve glycolipids metabolism and insulin resistance of obese and type 2 diabetes mellitus (T2DM) patients. This review mainly discusses the significance of brown and beige adipose tissues in the treatment of obesity and T2DM, and focuses on the effect of the browning agent on obesity and T2DM, which provides a brand-new theoretical reference for the prevention and treatment of obesity and T2DM.

4.
Eur J Hosp Pharm ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414258

RESUMO

BACKGROUND: There is a significant correlation between augmented renal clearance (ARC) and lower serum trough concentrations of vancomycin (VCM) during therapy. There is a need to evaluate the predictive performance of the population pharmacokinetic (PPK) model used for individual calculation of dosage regimens in ARC patients. OBJECTIVE: Our study aimed to estimate the predictive performance differences of the reported VCM PPK software JPKD-vancomycin and SmartDose in patients with varying renal function status, especially those with ARC. METHODS: Patients receiving VCM treatment from May 2014 to December 2019 were enrolled, and divided into the ARC group, the normal renal function (NRF) group, and the impaired renal function (IRF) group. VCM dosage, trough concentration, area under the curve (AUC) and pharmacokinetic parameters were compared among the three groups. The predictive performance of PPK software was expressed using absolute prediction error (APE), sensitivity, specificity, and regression coefficient (r2) of linear regression analysis between the measured VCM trough concentration and the predicted trough concentration. RESULTS: A total of 388 patients were included: 86 patients in the ARC group, 241 patients in the NRF group, and 61 patients in the IRF group. The daily dose of the adjusted regimen in the ARC group was higher than in the NRF group, but the trough concentration was significantly lower than in the NRF group (2.8±0.6 g vs 1.9±0.6 g, p<0.001; 10.5±5.1 mg/L vs 12.9±6.8 mg/L, p=0.030). The percentage of trough concentrations lower than 10 mg/L was 84.9% in the ARC group. Compared with the APE of the initial dosage regimen, the APE of the adjusted regimen calculated by JPKD was lower in the ARC group (p=0.041) and the NRF group (p<0.001). Specificity of JPKD and SmartDose in the ARC group was higher than in the NRF group (p<0.001; p<0.001). According to the linear regression analysis, the coefficients of determination (r2) were all >0.6 for the initial regimen and adjusted regimen of VCM in the ARC and NRF groups, and the r2 of the adjusted regimen of JPKD was >0.8 in the ARC and NRF groups. In the IRF group, 31.1% of patients had a change in serum creatinine (Scr) level of >50%. The r2 increased from 0.527 to 0.7347 in SmartDose and from 0.55 to 0.7802 in JPKD when using Scr at the sampling time. The ARC group showed a significant decrease in AUC (p<0.001) and an increase in clearance rate (p<0.001) when compared to the NRF group. CONCLUSION: ARC was significantly associated with subtherapeutic serum VCM concentration. The pharmacokinetic parameters of VCM were diverse in patients with different renal function status. The PPK model JPKD and SmartDose had a good predictive performance for predicting VCM trough concentrations of the ARC and NRF patients, especially using JPKD for prediction of the adjusted regimen. The change of Scr is a main factor affecting the accuracy of software prediction.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33386974

RESUMO

INTRODUCTION: Patient-specific instrumentation (PSI) utilizes three-dimensional imaging to produce total knee arthroplasty cutting jigs which matches patient's native anatomy. However, there are limited mid- to long-term studies examining its clinical efficacy. The aim of this study was to compare functional outcomes of PSI surgery versus conventional TKA surgery at 5-year follow-up. MATERIALS AND METHODS: Sixty patients were prospectively recruited into either the MRI-based PSI or conventional TKA group. Functional outcomes were assessed using the Knee Society Function Score (KSFS), Knee Society Knee Score (KSKS) and Oxford Knee Score (OKS), while quality of life was evaluated with the Physical Component Score (PCS) and Mental Component Score (MCS) of Short-Form 36 and compared between the two groups at 5-year follow-up. RESULTS: Although the PCS was 7 ± 3 points better in the PSI group preoperatively (p = 0.017), it became 5 ± 2 points worse than the conventional group at 5-year follow-up (p = 0.025). As compared to the PSI group, the conventional group showed a significantly greater improvement in PCS at 5 years as compared to before surgery (p = 0.003). There were no significant differences in KSFS, KSKS, OKS or MCS between the two groups. CONCLUSIONS: PSI TKA did not result in improved functional outcomes or better quality of life when compared to conventional TKA. The additional costs and waiting time associated with PSI are not justifiable and therefore not recommended as an alternative to conventional TKA. LEVEL OF EVIDENCE: II.

6.
Chem Commun (Camb) ; 57(4): 476-479, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33326521

RESUMO

Replacing coenzyme F430, an Ni(i) F430-like cofactor derived from vitamin B12 (F430-B12) is revealed by DFT calculations to be able to catalyze methane formation in methyl-coenzyme M reductase with a barrier of 13.3 kcal mol-1, demonstrating the correctness of the route starting from vitamin B12. The structure-activity relationships of F430 and F430-B12 (especially the roles of the F ring) are discovered and several sources of inspiration promoting the application of F430-B12 are also obtained, coming closer to using F430 chemistry in man-made catalysis.


Assuntos
Metaloporfirinas/química , Oxirredutases/química , Vitamina B 12/análogos & derivados , Proteínas Arqueais/química , Proteínas Arqueais/metabolismo , Domínio Catalítico , Cristalografia por Raios X , Teoria da Densidade Funcional , Metaloporfirinas/metabolismo , Metano/biossíntese , Methanobacteriaceae/enzimologia , Modelos Químicos , Estrutura Molecular , Níquel/química , Oxirredutases/metabolismo , Ligação Proteica , Relação Estrutura-Atividade , Termodinâmica , Vitamina B 12/metabolismo
7.
BMJ Open ; 10(12): e042578, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33323447

RESUMO

OBJECTIVES: Universities are exploring strategies to mitigate the spread of COVID-19 prior to reopening their campuses. National guidelines do not currently recommend testing students prior to campus arrival. However, the impact of presemester testing has not been studied. DESIGN: Dynamic SARS-CoV-2 transmission models are used to explore the effects of three presemester testing interventions. INTERVENTIONS: Testing of students 0, 1 and 2 times prior to campus arrival. PRIMARY OUTCOMES: Number of active infections and time until isolation bed capacity is reached. SETTING: We set on-campus and off-campus populations to 7500 and 17 500 students, respectively. We assumed 2% prevalence of active cases at the semester start, and that one-third of infected students will be detected and isolated throughout the semester. Isolation bed capacity was set at 500. We varied disease transmission rates (R0=1.5, 2, 3, 4) to represent the effectiveness of mitigation strategies throughout the semester. RESULTS: Without presemester screening, peak number of active infections ranged from 4114 under effective mitigation strategies (R0=1.5) to 10 481 under ineffective mitigation strategies (R0=4), and exhausted isolation bed capacity within 10 (R 0 =4) to 25 days (R0=1.5). Mandating at least one test prior to campus arrival delayed the timing and reduced the size of the peak, while delaying the time until isolation bed capacity was reached. Testing twice in conjunction with effective mitigation strategies (R0=1.5) was the only scenario that did not exhaust isolation bed capacity during the semester. CONCLUSIONS: Presemester screening is necessary to avert early and large surges of active COVID-19 infections. Therefore, we recommend testing within 1 week prior to and on campus return. While this strategy is sufficient for delaying the timing of the peak outbreak, presemester testing would need to be implemented in conjunction with effective mitigation strategies to significantly reduce outbreak size and preserve isolation bed capacity.


Assuntos
/diagnóstico , Controle de Doenças Transmissíveis/métodos , Programas de Rastreamento/métodos , Modelos Teóricos , Surtos de Doenças/prevenção & controle , Humanos , South Carolina , Estudantes/estatística & dados numéricos , Universidades/organização & administração
8.
Eye (Lond) ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33221815

RESUMO

PURPOSE: Teprotumumab, a blocking antibody to the insulin like growth factor 1 receptor (IGF-1R) has been shown to significantly reduce proptosis in recent phase 2 and 3 trials in patients with inflammatory thyroid eye disease (TED). Herein, we investigate the impact of teprotumumab on patients with non-inflammatory TED. We also investigate the expression of the IGF-1R on orbital tissues from patients with inflammatory and non-inflammatory TED compared to controls. METHODS: Consecutive patients with non-inflammatory TED (clinical activity score, CAS ≤ 1, for at least 4 months, were treated with teprotumumab. They received a complete course (total eight infusions) of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for subsequent infusions every 3 weeks). The primary outcome was a proptosis response at week 24. Further, IGF-1R α and ß expression was evaluated on orbital tissue from patients with inflammatory and non-inflammatory TED, as well as healthy controls. Non-biased histological analysis of IGF-1R expression was performed using ImageJ. RESULTS: Four patients met eligibility criteria for the clinical study, with a mean (SD) CAS of 0 (0). Following teprotumumab treatment, there was a mean (SD) reduction in proptosis of 2.6 mm (1.2). Five patients were included for each group of the histological study; inflammatory TED, non-inflammatory TED and controls. IGF-1Rα and IGF-1Rß expression was significantly greater in the orbital tissues of patients with inflammatory TED and non-inflammatory TED, when compared to controls. CONCLUSION: Our findings demonstrate for the first time, that teprotumumab, a blocking antibody to the IGF-1R reduces proptosis in a series of patients with non-inflammatory TED. Overexpression of the IGF-1R in orbital tissue from patients with non-inflammatory disease compared to controls may be an important consideration for effect.

9.
Phlebology ; : 268355520973488, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201775

RESUMO

OBJECTIVES: The present study was designed to assess outcomes of patients undergone radiofrequency ablation (RFA) for their incompetent perforator veins (IPVs) with ClosureFast stylets. METHODS: Data of 165 IPVs in 138 limbs of 117 consecutive patients between July 2017 to Nov. 2019 were retrospectively reviewed. Primary endpoints (technical success rate, complications) and secondary endpoints (VCSS) were analyzed. RESULTS: The immediate technical success rate was 100%. There were no major complications. The rate of ecchymosis and induration was 5.8%. 129/165 IPVs in 79.5% (93/117) patients had achieved sonographic evaluation at 1 year followed-up, in which 3 perforators were recanalized. VCSS scores at pre-operation and 1-year follow-up were 5.77 ± 1.88 and 2.70 ± 1.39, respectively (t= 29.644, P= .000). CONCLUSIONS: In conclusion, RFA is safe and effective for the treatment of IPVs. At the 1-year follow-up, the RFA of IPVs showed a low recanalization rate and had a satisfactory improvement on VCSS.

10.
Knee ; 27(6): 1914-1922, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221689

RESUMO

BACKGROUND: A sizeable proportion of knee osteoarthritis is limited to the medial and patellofemoral compartments. Whilst short- and medium-term studies comparing bicompartmental knee arthroplasty (BCA) and total knee arthroplasty (TKA) have shown similar outcome scores, there are no studies comparing long-term outcomes. This study aims to determine which procedure resulted in superior long-term outcome scores. METHODS: Forty-eight patients with medial and patellofemoral compartment knee osteoarthritis were randomised to receive treatment in two groups: unlinked, modular BCA and TKA. The main outcome measures compared were the range of motion, Knee Society Function Score, Knee Society Knee Score, Oxford Knee Score, Physical Component Score and Mental Component Score of SF-36 pre-operatively and post-operatively up to 10 years. Radiographs of the operated knees were taken pre-operatively, post-operatively and at 10-year follow-up. RESULTS: Twenty-six underwent BCA and 22 underwent TKA. Overall improvement was seen in both groups compared to pre-operatively, however there were no significant differences detected between the groups at 10 years. The median Hip-Knee-Ankle (HKA) angle was 183.38 (175.17-187.94) in the BCA group and 180.73 (174.96-185.65) in the TKA group. One patient from the BCA group had a peri-prosthetic fracture necessitating revision surgery to a TKA. CONCLUSIONS: Outcome scores for BCA results were comparable to TKA at long-term follow-up. BCA is an alternative arthroplasty option in selected patients.

11.
J Hepatol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212090

RESUMO

BACKGROUND AND AIMS: Little is known about EBV-associated intrahepatic cholangiocarcinoma (EBVaICC) due to its rarity. We aimed to comprehensively investigate the clinicopathology, tumor immune microenvironment (TIME) and genomic landscape of this entity in southern China. METHODS: We evaluated 303 ICCs using in situ hybridization for EBV, we compared clinicopathological parameters between EBVaICC and nonEBVaICC, and we analyzed EBV infection status, tumor-infiltrating lymphocytes (TILs) and genomic features of EBVaICC by immunohistochemistry, double staining, nested PCR, multiplex immunofluorescence staining, fluorescence in situ hybridization and whole exome sequencing. RESULTS: EBVaICC accounted for 6.6% of ICCs, with EBV latency type I infection and clonal EBV isolates form. Distinctive clinicopathological characteristics of EBVaICC included female predominance, younger patient predominance, solitary tumor, higher HBV infection rate, lower cirrhotic background and increased lymphoepithelioma-like (LEL) subtype proportion. EBVaICC had a significantly larger TIME component than nonEBVaICC. The LEL subtype of EBVaICC, which had a significantly increased density and proportion of CD20+ B cells and CD8+ T cells, was significantly related to longer 2-year OS and RFS than EBVaICC conventional type and nonEBVaICC. Both PD-1 and PD-L1 in TILs and PD-L1 in tumor cells were overexpressed in EBVaICC. Tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was significantly more common in EBVaICC than in nonEBVaICC. Mutated genes in at least three cases, including MUC4, DNAH1, GLI2, LIPE, MYH7, RP11-766F14.2 and WDR36, were uncovered. EBVaICC had different mutational pattern compared with reported liver fluke-associated cholangiocarcinoma and HBV-associated ICC. CONCLUSIONS: EBVaICC, as a subset of ICC, has unique etiological characteristics, clinicopathology and molecular genetics with a significantly larger TIME component. Most cases belong to TMIT I. Paradoxically, patients with EBVaICC could be candidates for immune checkpoint therapy.

12.
Contemp Clin Trials ; 99: 106182, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33080378

RESUMO

The opioid misuse epidemic has reached a crisis level in the United States. Though mindfulness-based relapse prevention (MBRP) has been shown as effective in treating substance use disorders, there is limited research on its application to opioid use disorders specifically, and there is a need to understand the underlying mechanisms. This paper outlines a protocol for a randomized controlled trial of MBRP for opioid use disorders. MBRP is a group aftercare program that integrates mindfulness skills training with cognitive-behavioral relapse prevention strategies. We will recruit 240 participants who have completed opioid use disorder treatment, and randomize them to an 8-week MBRP group intervention or treatment as usual (TAU) control group. The TAU control group will complete the intervention after 8 weeks. Assessments will take place at baseline, 8 weeks, and 16 weeks. The primary outcome is frequency of opioid use. The secondary outcomes include craving and withdrawal symptoms, time to first opioid use, adherence to medication-assisted treatment plans, perceived stress, quality of life, posttraumatic stress symptoms, and chronic pain. We will also examine the following potential moderators and correlates of intervention outcomes: comorbid diagnoses, life events history, and MBRP intervention adherence. In addition, we will examine the following mediators of intervention outcome: mindfulness skills, emotion regulation skills, executive functioning skills, savoring, and positive and negative affect. This study will contribute to the evidence base regarding MBRP's efficacy in reducing opioid use, as well as contribute to the understanding of the causal mechanisms and factors that modify treatment outcome for MBRP for substance use disorders.

13.
Front Pharmacol ; 11: 571906, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013415

RESUMO

Aim: To identify common drug-related problems (DRPs) during pharmacy intervention and consultation in an intensive care unit (ICU); to explore the gap between physicians and pharmacists on their understanding of each other's capabilities and needs. Method: We conducted a single-center prospective study in the ICU of a tertiary academic hospital for 21 months. A pharmaceutical care (PC) model was implemented by a pharmacy team, and data were collected during pharmacy intervention and consultation. Data analysis was performed on identified DRPs, causes and their relationships. DRPs' frequency during intervention and consultation was compared. Problem-level descriptive analysis and network analysis were conducted using R 3.6.3. Result: Implementation of PC model greatly improved the efficacy of pharmacists in both interventions proposed to solve DRPs (from 13.6 to 20.1 cases per month) and number of patients being closely monitored (from 7.7 to 16.9 per month). Pharmacists identified 427 DRPs during pharmacy intervention with primarily adverse drug events (ADEs, 34.7%) and effect of treatment not optimal (25.5%), and 245 DRPs during consultation (mainly ADEs, 58.4%). About three-fifths DRPs were caused by antibiotics. Comparing DRPs identified during pharmacy intervention and consultation, physicians consulted pharmacists more on questions related to medication safety, while pharmacists also paid attention to treatment effectiveness, which was consulted less commonly. Conclusion: Implementation of PC model is beneficial in guiding pharmacy practice and improving efficacy especially under limited human resources. Physicians and pharmacists shall continue ensuring drug safety and be familiar with the scope of PC and clinical need for a better cooperation.

14.
Inorg Chem ; 59(20): 15167-15179, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33017144

RESUMO

The biological synthesis of acetyl-coenzyme A (acetyl-CoA), catalyzed by acetyl-CoA synthase (ACS), is of biological significance and chemical interest acting as a source of energy and carbon. The catalyst contains an unusual hexa-metal cluster with two nickel ions and a [Fe4S4] cluster. DFT calculations have been performed to investigate the ACS reaction mechanism starting from three different oxidation states (+2, +1, and 0) of Nip, the nickel proximal to [Fe4S4]. The results indicate that the ACS reaction proceeds first through a methyl radical transfer from cobalamin (Cbl) to Nip randomly accompanying with the CO binding. After that, C-C bond formation occurs between the Nip-bound methyl and CO, forming Nip-acetyl. The substrate CoA-S- then binds to Nip, allowing C-S bond formation between the Nip-bound acetyl and CoA-S-. Methyl transfer is rate-limiting with a barrier of ∼14 kcal/mol, which does not depend on the presence or absence of CO. Both the Nip2+ and Nip1+ states are chemically capable of catalyzing the ACS reaction independent of the state (+2 or +1) of the [Fe4S4] cluster. The [Fe4S4] cluster is not found to affect the steps of methyl transfer and C-C bond formation but may be involved in the C-S bond formation depending on the detailed mechanism chosen. An ACS active site containing a Nip(0) state could not be obtained. Optimizations always led to a Nip1+ state coupled with [Fe4S4]1+. The calculations show a comparable activity for Nip1+/[Fe4S4]1+, Nip1+/[Fe4S4]2+, and Nip2+/[Fe4S4]2+. The results here give significant insights into the chemistry of the important ACS reaction.

15.
Analyst ; 145(21): 6992-6999, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-32869791

RESUMO

As an important and universal tumor marker, the reliable and in situ detection of intracellular telomerase activity is crucial for cancer diagnosis. Herein, a ratiometric fluorescence resonance energy transfer (FRET) method was developed for detecting intracellular telomerase activity. It takes full advantage of manganese dioxide nanosheets (MnO2NS) that can carry DNA probes with different conformations into cells and then completely release the DNA probes via decomposition of MnO2NS by intracellular reduced glutathione (GSH). In the presence of telomerase, a telomere substrate (TS) could be extended to form long telomerase extension products (TEPs), which trigger the cycling strand displacement reaction (SDR) between two fluorophore-labeled hairpin DNA probes to form lots of DNA duplexes. The close contact of two fluorophores led to an effective ratiometric FRET for reliable detection of telomerase activity. Fluorescence confocal imaging demonstrated that the activity of telomerase in tumor cells was reliably detected. The inhibition of telomerase activity by an inhibitor resulted in a decrease in FRET signal. For extracellular detection, the FRET ratio (FA/FD) shows a good linear relationship with the number of HeLa cells in the range of 20-1000 cells. Therefore, it offers a more facile method for reliable and sensitive detection of intracellular telomerase activity.

16.
J Pharm Biomed Anal ; 191: 113613, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32971496

RESUMO

In our present experiment, the aim of this paper was to develop and fully validate an accurate and simple ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for simultaneous quantification of acalabrutinib, ibrutinib, and their metabolites (ACP-5862 and PCI-45227) in beagle dog plasma and to survey the pharmacokinetic study of all analytes in beagle dogs. After a quick protein precipitation with acetonitrile, the chromatographic separation of acalabrutinib, ACP-5862, ibrutinib, PCI-45227 and bosutinib (internal standard, IS) were finished on an Acquity BEH C18 (2.1 mm × 50 mm, 1.7 µm) column and their detections were conducted by a Xevo TQ-S triple quadrupole tandem mass spectrometer in the positive ion mode. The assay displayed excellent linearity in the calibration range of 0.5-300 ng/mL for acalabrutinib, 0.5-30 ng/mL for ACP-5862, and 0.5-200 ng/mL for both ibrutinib and PCI-45227, respectively. Notably, the lower limit of quantification (LLOQ) for each compound was determined to be 0.5 ng/mL. The accuracy of all analytes for intra- and inter-day ranged from -4.3% to 14.6%, while precision were ≤9.0%. The recovery of each substance was > 81.0%, and no significant matrix effects were observed. The stabilities of all analytes under different conditions met all requirements for the quantitation in plasma samples. In addition, our developed UPLC-MS/MS method could also be employed to measure the pharmacokinetic profiles of acalabrutinib, ACP-5862, ibrutinib, and PCI-45227 in beagle dog plasma.

17.
Proc Natl Acad Sci U S A ; 117(39): 24352-24358, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32929014

RESUMO

Predicted increases in global average temperature are physiologically trivial for most endotherms. However, heat waves will also increase in both frequency and severity, and these will be physiologically more important. Lactating small mammals are hypothesized to be limited by heat dissipation capacity, suggesting high temperatures may adversely impact lactation performance. We measured reproductive performance of mice and striped hamsters (Cricetulus barabensis), including milk energy output (MEO), at temperatures between 21 and 36 °C. In both species, there was a decline in MEO between 21 and 33 °C. In mice, milk production at 33 °C was only 18% of that at 21 °C. This led to reductions in pup growth by 20% but limited pup mortality (0.8%), because of a threefold increase in growth efficiency. In contrast, in hamsters, MEO at 33 °C was reduced to 78.1% of that at 21 °C, yet this led to significant pup mortality (possibly infanticide) and reduced pup growth by 12.7%. Hamster females were more able to sustain milk production as ambient temperature increased, but they and their pups were less capable of adjusting to the lower supply. In both species, exposure to 36 °C resulted in rapid catastrophic lactation failure and maternal mortality. Upper lethal temperature was lowered by 3 to 6 °C in late lactation, making it a critically sensitive window to high ambient temperatures. Our data suggest future heat wave events will impact breeding success of small rodents, but this is based on animals with a long history in captivity. More work should be performed on wild rodents to confirm these impacts.

18.
World J Surg Oncol ; 18(1): 244, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917215

RESUMO

BACKGROUND: Postoperative atrial fibrillation (POAF) is one of the most common complications of esophagectomy, which may extend the inpatient hospital stay. Minimally invasive esophagectomy (MIE) has been increasingly used in clinical practice; however, its POAF risk and short-term mortality remain unclear. This study aimed to examine the POAF risk and in-hospital mortality rate between patients receiving MIE and open esophagectomy (OE). METHODS: Esophageal cancer patients who underwent MIE or OE from a retrospective cohort study were evaluated. A multivariate logistic regression model was built to assess the associations between esophagectomy (MIE vs. OE) and various outcomes (POAF, in-hospital mortality). Covariates included age, sex, body mass index, neoadjuvant therapy, tumor stage, surgery incision type, comorbidities, cardia conditions, peri-operative medication, and complications. RESULTS: Of the 484 patients with esophageal cancer, 63 received MIE. A total of 53 patients developed POAF. Compared to patients receiving OE, MIE patients had 81% reduced odds of POAF (adjusted odds ratio [aOR] 0.185, 95% CI 0.039-0.887, P = 0.035). No statistically significant association was found for in-hospital mortality (aOR 0.709, 95% CI 0.114-4.409, P = 0.712). CONCLUSIONS: MIE is associated with a lower risk of POAF, compared to traditional surgery. No significant short-term survival benefit was found for MIE.

19.
J Stroke Cerebrovasc Dis ; 29(10): 105106, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32912515

RESUMO

INTRODUCTION: Previous studies have reported a "weekend effect" on stroke mortality, whereby stroke patients admitted during weekends have a higher risk of in-hospital death than those admitted during weekdays. AIMS: We aimed to investigate whether patients with different types of stroke admitted during weekends have a higher risk of in-hospital mortality in rural and urban hospitals in the US. METHODS: We used data from the 2016 National Inpatient Sample and used logistic regression to assess in-hospital mortality for weekday and weekend admissions among stroke patients aged 18 and older by stroke type (ischemic or hemorrhagic) and rural or urban status. RESULTS: Crude stroke mortality was higher in weekend admissions (p <0.001). After adjusting for confounding variables, in-hospital mortality among hemorrhagic stroke patients was significantly greater (22.0%) for weekend admissions compared to weekday admissions (20.2%, p = 0.009). Among rural hospitals, the in-hospital mortality among hemorrhagic stroke patients was also greater among weekend admissions (36.9%) compared to weekday admissions (25.7%, p = 0.040). Among urban hospitals, the mortality of hemorrhagic stroke patients was 21.1% for weekend and 19.6% for weekday admissions (p = 0.026). No weekend effect was found among ischemic stroke patients admitted to rural or urban hospitals. CONCLUSIONS: Our results help to understand mortality differences in hemorrhagic stroke for weekend vs. weekday admissions in urban and rural hospitals. Factors such as density of care providers, stroke centers, and patient level risky behaviors associated with the weekend effect on hemorrhagic stroke mortality need further investigation to improve stroke care services and reduce weekend effect on hemorrhagic stroke mortality.


Assuntos
Plantão Médico , Isquemia Encefálica/mortalidade , Mortalidade Hospitalar , Hospitais Rurais , Hospitais Urbanos , Hemorragias Intracranianas/mortalidade , Acidente Vascular Cerebral/mortalidade , Adolescente , Adulto , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Pacientes Internados , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/terapia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
20.
Nutr Metab Cardiovasc Dis ; 30(12): 2215-2220, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-32912788

RESUMO

BACKGROUND AND AIMS: It has been reported that elevated serum uric acid (SUA) is related to inflammation and potentially to platelet hyper-reactivity. However, the relationship between elevated SUA and residual platelet reactivity is uncertain in patients on dual antiplatelet treatment (DAPT) with aspirin and clopidogrel. METHODS AND RESULTS: A cross-sectional cohort study was conducted on 2569 patients undergoing DAPT with aspirin and clopidogrel. Patients' SUA levels, residual platelet aggregation, routine blood tests and clinical characteristics were recorded. The relationship between SUA level and residual platelet aggregation was assessed by correlation analysis, and the relationship between SUA level and the prevalence of clopidogrel low response (CLR) was assessed by multivariate logistic regression analysis. Adenosine diphosphate (ADP) induced platelet aggregation (PLADP) was higher in normal-SUA group than that in hyperuricemia group [30(21, 40) % vs. 27(19, 39) %, p = 0.032]. No significant difference was found for arachidonic acid (AA) induced platelet aggregation (PLAA) between the two groups [4(2, 5) % vs. 3(2, 5) %, p = 0.557]. The correlation between SUA and PLADP was statistically significant(r = -0.115, p < 0.001), while that between SUA and PLAA was non-significant (r = -0.012, p = 0.643). Using the multivariate logistic regression analysis, higher SUA concentration was associated with a decreased risk of clopidogrel low response (CLR) (OR [95%CI] = 0.997 [0.995-0.999], p = 0.001). CONCLUSION: This is the largest study to date showing that in patients receiving DAPT with aspirin and clopidogrel, SUA is independently and negatively associated with the prevalence of clopidogrel low response. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov Unique Identifier: NCT01955200.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...