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1.
Nat Commun ; 12(1): 2016, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795671

RESUMO

We report the identification of three structurally diverse compounds - compound 4, GC376, and MAC-5576 - as inhibitors of the SARS-CoV-2 3CL protease. Structures of each of these compounds in complex with the protease revealed strategies for further development, as well as general principles for designing SARS-CoV-2 3CL protease inhibitors. These compounds may therefore serve as leads for the basis of building effective SARS-CoV-2 3CL protease inhibitors.

2.
J Biol Chem ; : 100530, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33713704

RESUMO

Phytol is the isoprenoid alcohol bound in ester linkage to chlorophyll, the most abundant photosynthetic pigment in plants. During leaf senescence, large amounts of phytol are released by chlorophyll degradation. However, the pathway of phytol catabolism in plants is unknown. We hypothesized that phytol degradation in plants might involve its oxidation into the long chain aldehyde phytenal. Using gas chromatography-mass spectrometry for aldehyde quantification after derivatization with methylhydroxylamine, phytenal was identified in leaves, while other long chain aldehydes (phytanal, pristanal) were barely detectable. We found that phytenal accumulates during chlorotic stresses, e.g. salt stress, dark-induced senescence and nitrogen deprivation. The increase in phytenal content is mediated at least in part independently of enzyme activities, and it is independent of light. Characterization of phytenal accumulation in the pao1 mutant affected in chlorophyll degradation revealed that phytenal is an authentic phytol metabolite derived from chlorophyll breakdown. The increase in phytenal was even stronger in mutants affected in the production of other phytol metabolites including vte5-2 (tocopherol deficient) and pes1 pes2 (fatty acid phytyl ester deficient). Therefore, phytenal accumulation is controlled by competing, alternative pathways of phosphorylation (leading to tocopherol production) or esterification (fatty acid phytyl ester production). As a consequence, the content of phytenal is maintained at low levels, presumably to minimize its toxic effects caused by its highly reactive aldehyde group that can form covalent bonds with and inactivate the amino groups of proteins.

3.
Small ; : e2005241, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33734595

RESUMO

Magnetic hyperthermia (MH) harnesses the heat-releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium-89-positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21-87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat-shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti-tumor immune response.

4.
Nanotechnology ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33721843

RESUMO

Point defects may significantly influence the electrical and optoelectronic properties of two-dimensional tungsten diselenide (WSe2), while precise information about point defects distribution (e.g., species and concentration) in monolayer (ML-) WSe2 are hard to obtain. In this letter, we tried to partly fill this knowledge gap via performing quantitative and statistical analysis of intrinsic point defects in WSe2 monolayers prepared by three so-called main-stream approaches i.e., mechanical exfoliation (ME), chemical vapor deposition (CVD), and molecular beam epitaxy (MBE), which are promising for providing high-quality samples. Via a conjunction of statistic atomic-resolution annular dark-field scanning transmission electron microscopy (ADF-STEM) imaging, software-based automated defect identification and counting, together with image simulations, defect species and concentrations were quantitatively determined. Seven types of intrinsic point defects were identified in ML-WSe2 and the most dominant one is selenium mono-vacancy (VSe) (corresponding to one Se atom missing), irrespective of the synthetic route and growth conditions. Exact contents and diversity of point defects depend on the specific preparation method: CVD grown ML-WSe2 is the most defective (for example, the density of VSe reaches 1.40% in atomic ratio), followed by ME (~ 0.79 at% for VSe) and MBE grown samples (~ 0.42 at% for VSe). Our results, though still with limited sampling, provide preliminary quantitative information of point defects in ML-WSe2, which can serve as a reference to achieve the precisely controlled large-scale sample growth and establish the structure-property relationship of two-dimensional transition-metal dichalcogenides (2D TMDCs) materials.

5.
J Biol Chem ; : 100382, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33556369

RESUMO

Topoisomerase IIß-binding protein 1 (TopBP1) is involved in cellular replication among other functions, and is known to activate ATR/Chk1 during replicative stress. TopBP1 is also expressed at high levels in many cancers. However, the impact of TopBP1 overexpression on ATR/Chk1 activation and cancer development has not been investigated. Here we demonstrate that the degree of ATR/Chk1 activation is regulated by TopBP1 in a biphasic, concentration-dependent manner in a non-transformed MCF10A cell line and several cancer cell lines, including H1299, MDA-MB468 and U2OS. At low levels, TopBP1 activates ATR/Chk1, but once TopBP1 protein accumulates above an optimal level, it paradoxically leads to lower activation of ATR/Chk1. This is due to the perturbation of ATR/TopBP1 interaction and ATR chromatin loading by excessive TopBP1. Overexpression of TopBP1 thus hinders the ATR/Chk1 checkpoint response, leading to the impairment of genome integrity as demonstrated by the cytokinesis-block micronucleus assay. In contrast, moderate depletion of TopBP1 by shRNA in TopBP1-overexpressing cancer cells enhanced ATR/Chk1 activation and S-phase checkpoint response after replicative stress. The clinical significance of these findings is supported by an association between TopBP1 overexpression and genome instability in many types of human cancer. Taken together, our study illustrates an unexpected relationship between the levels of TopBP1 and the final functional outcome, and suggests TopBP1 overexpression as a new mechanism directly contributing to genomic instability during tumorigenesis.

6.
Mayo Clin Proc ; 96(2): 350-362, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33549256

RESUMO

OBJECTIVE: To evaluate the association between the use of cholinesterase inhibitors (ChEIs) and incident cardiovascular events (CVEs) among older patients with Alzheimer disease (AD). PATIENTS AND METHODS: This retrospective cohort study was conducted with a new-user design and active-comparator design. The data source was the 2005-2014 Full Population file from the Health and Welfare Database in Taiwan. Patients were included if they were aged 50 years or older and had been diagnosed with AD between January 1, 2006, and December 31, 2010. The association between ChEI use and the risk of CVEs was investigated in patients with AD. Among the ChEI users, the risk of CVEs was further compared between patients with different cumulative doses and different ChEI treatment strategies. The propensity score method, which included matching and inverse probability of treatment weighting, was used to balance the potential confounders. A Cox proportional hazards model with competing risks was used to estimate the hazard ratio of CVEs. RESULTS: The study included 6070 patients with AD. After covariate adjustment, ChEI users had a significantly lower risk of CVEs than nonusers (hazard ratio, 0.57; 95% CI, 0.51 to 0.62). Among ChEI users, patients with a high cumulative dose had a significantly lower risk of CVEs than those with a low cumulative dose (hazard ratio, 0.82; 95% CI, 0.70 to 0.96). CONCLUSION: The use of ChEIs was associated with a decreased risk of incident CVEs among patients with AD. The cardioprotective effect of ChEIs showed a dose-response relationship.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Inibidores da Colinesterase/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Colinesterase/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Taiwan/epidemiologia
7.
Cancer ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33631040

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC) is used in head and neck squamous cell carcinoma (HNSCC) for downstaging advanced disease and decreasing distant metastasis (DM). To the authors' knowledge, no study has specifically examined the impact of a delayed time to surgery (TTS) after NAC on oncologic outcomes. They thus aimed to identify a cutoff for TTS after NAC and its effect on survival indices. METHODS: This was a retrospective review of all patients with HNSCC receiving NAC followed by surgery with curative intent between March 2016 and March 2019 at the MD Anderson Cancer Center. Receiver operating characteristic analysis was used to identify a cutoff for TTS, and this cutoff was used to analyze the overall survival (OS), locoregional recurrence rate, DM-free rate, and disease-free survival (DFS). A multivariate Cox regression analysis was performed. RESULTS: One hundred one patients were analyzed with a median follow-up of 24.7 months. The 3-year OS and locoregional recurrence rates did not differ with a TTS ≥ 34 days. However, the 3-year DM-free rate was significantly worse (56% vs 90%; P = .001) in the group with a TTS ≥ 34 days, and the 3-year DFS was significantly lower (26% vs 64%; P = .006). In a multivariate analysis, a TTS ≥ 34 days (hazard ratio [HR], 4.92; 95% confidence interval [CI], 1.84-13.13) and extracapsular extension (HR, 3.01; 95% CI, 1.13-8.00) were significant independent predictors of a poorer DM-free rate. Weight loss > 10% (HR, 5.53; 95% CI, 1.02-30.24) was the only independent predictor for a TTS ≥ 34 days. CONCLUSIONS: Emphasis should be placed on early definitive locoregional treatment after NAC, particularly in patients who do not respond to NAC. There is a need to validate these findings and establish new benchmarks for the interval between NAC and surgery.

8.
J Formos Med Assoc ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33637370

RESUMO

BACKGROUND/PURPOSE: To compare the risk of acute kidney injury (AKI) among patients receiving teicoplanin (TA) plus piperacillin/tazobactam (TZP) versus vancomycin (VAN) plus TZP. METHODS: This was a retrospective cohort study using electronic health records. Patients were included if a combination of glycopeptide and TZP or other selected ß-lactams were used during hospitalization. In the main analysis, two study groups were identified: TA + TZP and VAN + TZP. We used 1:1 propensity score matching to control for potential confounders, and hazard ratio (HR) of AKI between study groups was calculated. We further compared the risk of AKI between patients receiving VAN + TZP and VAN + ß-lactams as an auxiliary analysis to verify the validity of the study design. RESULTS: The final sample contained 211 pairs of patients receiving either TA + TZP or VAN + TZP. The median dosage of TA and VAN were 10.3 and 26.7 mg/kg/day, respectively. The median trough level of VAN was 12.3 mg/L. The AKI risk in the TA + TZP group was similar to that in the VAN + TZP group (12.3% vs. 11.4%; HR = 1.25 [0.72-2.18], p = 0.44). The auxiliary analysis showed a higher risk of AKI in the VAN + TZP group than in the VAN + ß-lactam group (13.2% vs. 9.6%; HR = 1.63 [1.04-2.55], p = 0.03). CONCLUSION: Our study results showed that the risk of AKI were similar for patients receiving TA + TZP and VAN + TZP. However, low VAN and high TA dose may play a role in this finding. Further investigation on the association between AKI and TA + TZP is required.

9.
Public Health Nutr ; : 1-13, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33618790

RESUMO

OBJECTIVE: The current study evaluated the associations between different forms and sources of Fe and breast cancer risk in Southern Chinese women. DESIGN: Case-control study. We collected data on the consumption of Fe from different forms and food sources by using a validated FFQ. Multivariable logistic regression and restricted cubic spline (RCS) analysis was used to reveal potential associations between Fe intake and breast cancer risk. SETTING: A case-control study of women at three major hospitals in Guangzhou, China. PARTICIPANTS: From June 2007 to March 2019, 1591 breast cancer cases and 1622 age-matched controls were recruited. RESULTS: In quartile analyses, Fe from plants and Fe from white meat intake were inversely associated with breast cancer risk, with OR of 0·65 (95 % CI 0·47, 0·89, Ptrend = 0·006) and 0·76 (95 % CI 0·61, 0·96, Ptrend = 0·014), respectively, comparing the highest with the lowest quartile. No associations were observed between total dietary Fe, heme or non-heme Fe, Fe from meat or red meat and breast cancer risk. RCS analysis demonstrated J-shaped associations between total dietary Fe, non-heme Fe and breast cancer, and reverse L-shaped associations between heme Fe, Fe from meat and Fe from red meat and breast cancer. CONCLUSION: Fe from plants and white meat were inversely associated with breast cancer risk. Significant non-linear J-shaped associations were found between total dietary Fe, non-heme Fe and breast cancer risk, and reverse L-shaped associations were found between heme Fe, Fe from meat or red meat and breast cancer risk.

10.
Curr Med Res Opin ; 37(4): 535-542, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33538623

RESUMO

OBJECTIVE: We compared the effectiveness and safety outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients with AF and VHD, as these patients have been partially excluded from clinical trials. METHODS: This retrospective cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients with AF and VHD and above 20 years of age, who were prescribed oral anticoagulants such as warfarin, dabigatran, rivaroxaban, and apixaban, were included. Propensity score matching was performed to balance intergroup differences. The Cox proportional hazards model was used to compare the effectiveness and safety of warfarin and NOACs. RESULTS: We included 5833 NOAC-warfarin pairs, 3001 dabigatran-warfarin pairs and 2595 rivaroxaban-warfarin pairs. Warfarin and NOACs had similar risk of ischemic stroke (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.79-1.06; p = .25) and bleeding events (HR, 0.90; 95% CI, 0.78-1.02; p = .10). NOACs showed reduced risk of venous thromboembolism, intracranial hemorrhage, and mortality (HR and 95% CI, 0.39 [0.20-0.77], p = .01; 0.62 [0.45-0.84], p < .01; and 0.47 [0.41-0.53], p < .01, respectively). The benefit of NOACs in reducing the risk of venous thromboembolism was mainly driven by dabigatran, and the benefit of reducing the risk of intracranial hemorrhage and mortality was observed in both dabigatran and rivaroxaban users. CONCLUSIONS: NOACs had a comparable risk of ischemic stroke and bleeding in patients with AF and VHD, and reduced the risk of venous thromboembolism, intracranial hemorrhage, and mortality, compared to warfarin. Therefore, NOAC is an effective and safe alternative to warfarin in these patients.

11.
Stem Cells ; 39(4): 443-457, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33426760

RESUMO

ERG1, a potassium ion channel, is essential for cardiac action potential repolarization phase. However, the role of ERG1 for normal development of the heart is poorly understood. Using the rat embryonic stem cells (rESCs) model, we show that ERG1 is crucial in cardiomyocyte lineage commitment via interactions with Integrin ß1. In the mesoderm phase of rESCs, the interaction of ERG1 with Integrin ß1 can activate the AKT pathway by recruiting and phosphorylating PI3K p85 and focal adhesion kinase (FAK) to further phosphorylate AKT. Activation of AKT pathway promotes cardiomyocyte differentiation through two different mechanisms, (a) through phosphorylation of GSK3ß to upregulate the expression levels of ß-catenin and Gata4; (b) through promotion of nuclear translocation of nuclear factor-κB by phosphorylating IKKß to inhibit cell apoptosis, which occurs due to increased Bcl2 expression. Our study provides solid evidence for a novel role of ERG1 on differentiation of rESCs into cardiomyocytes.

12.
Aging (Albany NY) ; 13(3): 4157-4181, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33461170

RESUMO

According to cancer statistics reported in 2020, breast cancer constitutes 30% of new cancer cases diagnosed in American women. Histological markers of breast cancer are expressions of the estrogen receptor (ER), the progesterone receptor (PR), and human epidermal growth factor receptor (HER)-2. Up to 80% of breast cancers are grouped as ER-positive, which implies a crucial role for estrogen in breast cancer development. Therefore, identifying potential therapeutic targets and investigating their downstream pathways and networks are extremely important for drug development in these patients. Through high-throughput technology and bioinformatics screening, we revealed that coiled-coil domain-containing protein 167 (CCDC167) was upregulated in different types of tumors; however, the role of CCDC167 in the development of breast cancer still remains unclear. Integrating many kinds of databases including ONCOMINE, MetaCore, IPA, and Kaplan-Meier Plotter, we found that high expression levels of CCDC167 predicted poor prognoses of breast cancer patients. Knockdown of CCDC167 attenuated aggressive breast cancer growth and proliferation. We also demonstrated that treatment with fluorouracil, carboplatin, paclitaxel, and doxorubicin resulted in decreased expression of CCDC167 and suppressed growth of MCF-7 cells. Collectively, these findings suggest that CCDC167 has high potential as a therapeutic target for breast cancer.

13.
Chem Commun (Camb) ; 57(14): 1754-1757, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33470253

RESUMO

An antimony based luminescent organic-inorganic hybrid compound H3SbCl6(L)6 (1, L = 2-(3-methyl-1H-imidazol-3-ium-1-yl)acetate) has been prepared by the solvothermal method. It emits bright green light peaking at 525 nm, with an internal quantum yield (IQY) of 73% under 360 nm excitation. The negative thermal quenching (NTQ) effect has been observed in the temperature range of 77 K to 297 K. Due to its ionic structure, compound 1 is soluble in numerous organic solvents, including methanol, dimethyl sulfoxide (DMSO), etc. The solution processability combined with high quantum efficiency makes 1 a promising candidate as a luminescent coating material for optoelectronic devices.

14.
Proc Natl Acad Sci U S A ; 118(3)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33408251

RESUMO

Cisplatin is a mainstay of systemic therapy for a variety of cancers, such as lung cancer, head and neck cancer, and ovarian cancer. However, resistance to cisplatin represents one of the most significant barriers for patient outcome improvement. Actin-like 6A (ACTL6A) is a component of several chromatin remodeling complexes, including SWI/SNF, NuA4/TIP60 histone acetylase, and INO80. Amplification of ACTL6A gene is often seen in lung squamous cell carcinoma, ovarian cancer, and esophageal cancer, but its significance remains to be fully determined. Here we identify ACTL6A overexpression as a novel cause for platinum resistance. High levels of ACTL6A are associated with chemoresistance in several types of human cancer. We show that overexpression of ACTL6A leads to increased repair of cisplatin-DNA adducts and resistance to cisplatin treatment. In contrast, depletion of ACTL6A inhibits the repair of cisplatin-induced DNA lesions, and increases cisplatin sensitivity in cisplatin-resistant ovarian cancer cells. The regulation of repair by ACTL6A is mediated through the SWI/SNF chromatin remodeling complex. Treatment with a histone deacetylase inhibitor can reverse the effect of ACTL6A overexpression on the repair of cisplatin-induced DNA damage and render cancer cells more sensitive to cisplatin treatment in a xenograft mouse model. Taken together, our study uncovers a novel role for ACTL6A in platinum resistance, and provides evidence supporting the feasibility of using HDAC inhibitors for platinum resistant tumors.

15.
COPD ; 18(1): 16-25, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33455452

RESUMO

Gas exchange inefficiency and dynamic hyperinflation contributes to exercise limitation in chronic obstructive pulmonary disease (COPD). It is also characterized by an elevated fraction of physiological dead space (VD/VT). Noninvasive methods for accurate VD/VT assessment during exercise in patients are lacking. The current study sought to compare transcutaneous PCO2 (TcPCO2) with the gold standard-arterial PCO2 (PaCO2)-and other available methods (end tidal CO2 and the Jones equation) for estimating VD/VT during incremental exercise in COPD. Ten COPD patients completed a symptom limited incremental cycle exercise. TcPCO2 was measured by a heated electrode on the ear-lobe. Radial artery blood was collected at rest, during unloaded cycling (UL) and every minute during exercise and recovery. Ventilation and gas exchange were measured breath-by-breath. Bland-Altman analysis examined agreement of PCO2 and VD/VT calculated using PaCO2, TcPCO2, end-tidal PCO2 (PETCO2) and estimated PaCO2 by the Jones equation (PaCO2-Jones). Lin's Concordance Correlation Coefficient (CCC) was assessed. 114 measurements were obtained from the 10 COPD subjects. The bias between TcPCO2 and PaCO2 was 0.86 mmHg with upper and lower limit of agreement ranging -2.28 mmHg to 3.99 mmHg. Correlation between TcPCO2 and PaCO2 during rest and exercise was r2=0.907 (p < 0.001; CCC = 0.941) and VD/VT using TcPCO2 vs. PaCO2 was r2=0.958 (p < 0.0001; CCC = 0.967). Correlation between PaCO2-Jones and PETCO2 vs. PaCO2 were r2=0.755, 0.755, (p < 0.001; CCC = 0.832, 0.718) and for VD/VT calculation (r2=0.793, 0.610; p < 0.0001; CCC = 0.760, 0.448), respectively. The results support the accuracy of TcPCO2 to reflect PaCO2 and calculate VD/VT during rest and exercise, but not in recovery, in COPD patients, enabling improved accuracy of noninvasive assessment of gas exchange inefficiency during incremental exercise testing.

16.
Pharmacol Res ; 164: 105390, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33352227

RESUMO

Angiogenesis is rapidly initiated in response to pathological conditions and is a key target for pharmaceutical intervention in various malignancies. Anti-angiogenic therapy has emerged as a potential and effective therapeutic strategy for treating cancer and cardiovascular-related diseases. Metformin, a first-line oral antidiabetic agent for type 2 diabetes mellitus (T2DM), not only reduces blood glucose levels and improves insulin sensitivity and exerts cardioprotective effects but also shows benefits against cancers, cardiovascular diseases, and other diverse diseases and regulates angiogenesis. MicroRNAs (miRNAs) are endogenous noncoding RNA molecules with a length of approximately 19-25 bases that are widely involved in controlling various human biological processes. A large number of miRNAs are involved in the regulation of cardiovascular cell function and angiogenesis, of which miR-21 not only regulates vascular cell proliferation, migration and apoptosis but also plays an important role in angiogenesis. The relationship between metformin and abnormal miRNA expression has gradually been revealed in the context of numerous diseases and has received increasing attention. This paper reviews the drug-target interactions and drug repositioning events of metformin that influences vascular cells and has benefits on angiogenesis-mediated effects. Furthermore, we use miR-21 as an example to explain the specific molecular mechanism underlying metformin-mediated regulation of the miRNA signaling pathway controlling angiogenesis and vascular protective effects. These findings may provide a new therapeutic target and theoretical basis for the clinical prevention and treatment of cardiovascular diseases.

17.
Ann Pharmacother ; : 1060028020980417, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33305585

RESUMO

BACKGROUND: Whereas previous studies found that concomitant antidepressant and nonsteroidal anti-inflammatory drug (NSAIDs) use may increase the risk of gastrointestinal bleeding, either drug alone increases the risk of intracranial hemorrhage (ICH). OBJECTIVE: To assess the risk for ICH in patients on concomitant treatment with antidepressants and NSAIDs. METHODS: This was a nested case-control study using national insurance claims data in Taiwan between 2005 and 2013. Drug exposure was measured and compared during 3 time windows: 1 to 30, 31 to 60, and 61 to 90 days before the index date, which is the date of the ICH event. Both traditional and newer-generation antidepressants were considered in this study. RESULTS: Patients exposed to both antidepressants and NSAIDs 1 to 30 days before the index date presented a 50% increased odds of developing ICH (OR: 1.53; 95% CI: 1.31-1.80) compared with patients receiving antidepressants alone. Specifically, the concomitant use of nonselective NSAIDs and antidepressants increased these odds compared with antidepressants alone (OR: 1.56; 95% CI: 1.31-1.84), but using a selective cyclooxygenase-2 inhibitor with antidepressant did not alter ICH risk. Regarding antidepressant class, newer-generation antidepressants generally increase the odds of developing ICH by 60% when used concomitantly with NSAIDs. CONCLUSION AND RELEVANCE: Our results suggested that the concomitant use of antidepressants and NSAIDs was associated with an increased odds of developing ICH. NSAIDs, especially nonselective NSAIDs, and serotonergic antidepressants played an important role in this risk. Given the prevalent use of these 2 classes of drugs, this potential drug interaction deserves more attention.

18.
Sci Rep ; 10(1): 21835, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33318590

RESUMO

In patients with atherosclerotic cardiovascular disease (ASCVD) under statin treatment, the influence of on-treatment level of high-density lipoprotein cholesterol (HDL-C) on cardiovascular (CV) events is controversial. Statin-treated patients were selected from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry, a multicenter, observational study of adult patients with ASCVD in Taiwan. Low HDL-C was defined as < 40 mg/dL for men and < 50 mg/dL for women. The primary outcome was a composite CV events including CV death, myocardial infarction (MI), stroke or cardiac arrest with resuscitation. A total of 3731 patients (mean age 65.6 years, 75.6% men) were included. Patients with on-treatment low HDL-C (44%, mean HDL-C 34.9 ± 6.8 mg/dL) were younger and with more diabetes and higher body weight. The mean follow-up time was 2.7 years. We used restricted cubic spline curves to examine the potential non-linear association between HDL-C and adverse outcomes. Decreased HDL-C levels were associated with a significantly increased risk of CV events in women (< 49 mg/dL in women) but not in men (< 42 mg/dL in men). However, the protective effect of elevated HDL-C levels was more prominent in men than in women. In ASCVD patients with statin therapy, low on-treatment HDL-C was common in Taiwan and associated with an increased risk of CV events in women. Higher HDL-C levels provided more protective effect in men than in women.

19.
Ying Yong Sheng Tai Xue Bao ; 31(9): 2963-2976, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-33345497

RESUMO

Based on field experiments in 2017-2019, we examined the characteristics, yield effect and regulatory mechanism of light energy utilization in alfalfa/gramineous forage grass intercropping. With monoculture of alfalfa, forage triticale (C3 plant), and forage maize (C4 plant) as control, we measured the yield effect, the effect of light energy utilization factor on yield formation, the characteristic difference and mechanism of light energy utilization under alfalfa/triticale and alfalfa/maize intercropping patterns. Results showed that land equivalent ratios of both intercropping patterns were all greater than 1, indicating that land utilization ratio and yield benefit of the two intercropping patterns were higher than that of monoculture, among which alfalfa/triticale intercropping pattern was the most promising one. The contribution of light energy utilization factors to yield was following an order of leaf area index (1.531) > net photosynthetic rate (0.882) > intercellular CO2 concentration (0.282) > transpiration rate (-0.229) > canopy opening (-0.291) > PAR interception rate (-0.681) > stomatal conductance (-0.751). Among them, leaf area index was not only one of the important indices to characterize photosynthetic capacity, but also an important component factor of forage crop yield aiming at harvesting nutrients. Therefore, among all factors of photosynthetic characteristics, net photosynthetic rate was the main factor affecting yield. The net photosynthetic rate of alfalfa, triticale and maize under intercropping showed the same pattern, and being different from that of monoculture. The main ways for intercropping to increase net photosynthetic rate included: triticale and maize increased net photosynthetic rate and yield by enhancing the carboxylation fixation capacity of CO2 and the utilization capacity of strong light, while alfalfa could improve its net photosynthetic rate and promote growth under low light, by increasing the content of chlorophyll b in functional leaves, changing chlorophyll composition and enhancing the collection and transmission of light energy.


Assuntos
Agricultura , Medicago sativa , Fotossíntese , Folhas de Planta , Poaceae , Zea mays
20.
BMC Public Health ; 20(1): 1759, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228661

RESUMO

BACKGROUND: Although past studies have identified factors associated with individual perceptions of vaccination, limited attention has been paid to the role of personality in individual attitudes toward vaccination. This study aimed to evaluate the effect of personality as measured by the Big Five personality traits on individual attitudes toward vaccination using a nationally representative survey in the United States. METHODS: A cross-sectional study was conducted with a sample of 3276 American citizens who were aged 18 and above and lived in 50 U.S. states and Washington D.C. from the American National Election Studies. The survey was collected through face-to-face and online interviews using structured questionnaires in 2016. The multistage stratified cluster sampling procedure was used for face-to-face interview, whereas the USPS DSF was used to select the sample for online interview. Multivariable ordinal logistic regression was used to assess how personality traits (extraversion, agreeableness, conscientiousness, emotional stability, and openness to experience) as main explanatory variables influence the outcome variables - individual attitudes toward health benefits of vaccination and support for school vaccination. RESULTS: More than two-thirds of respondents perceive health benefit of vaccination and support vaccination requirements for school entry, whereas about one-tenth of respondents have safety concerns about vaccination and oppose the vaccination requirements. After adjusting for ideology, insurance status, and demographic variables, the traits of agreeableness, conscientiousness and emotional stability remain significantly associated with attitude toward vaccination; conscientiousness is significantly associated with support for school vaccination. The odds of reporting health benefits of vaccination associated with one-point increase in agreeableness, conscientiousness and emotional stability are 1.05 (95% confidence intervals [CI] = 1.01-1.08), 1.05 (95% CI = 1.02-1.09) and 1.03 (95% CI = 1.00-1.06), respectively. For a one-point increase in conscientiousness, the odds of supporting school vaccination increase by 1.08 (95% CI = 1.05-1.12). CONCLUSIONS: People high in agreeableness, conscientiousness and emotional stability are more likely to regard vaccination as beneficial, whereas those high in conscientiousness are more likely to support school-based vaccine requirement. This study highlights the importance of personality in shaping individual attitudes toward vaccination. More research is needed to understand the role of personality in individual health attitudes and behavior.

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