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1.
Front Public Health ; 9: 639273, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816424

RESUMO

Background: Despite the benefits of cardiac rehabilitation (CR), phase II CR remains highly unavailable; the factors influential to the successful implementation and development of phase II CR programs have not been fully explored. Methods: A cross-sectional survey was completed by 168 nationwide clinical staff. Parameters associated with the successful implementation and development of phase II CR and the factors associated with the quality of CR were explored by multivariable logistic regression. Results: One hundred and eighteen of 168 respondents' institutions had successfully developed phase II CR programs, 41 of which delivered high-quality CR. Independent factors associated with successful implementation and development of CR were leadership support from hospital administrators, support from resident physicians, staff perception in CR increasing medical risk, and department type (cardiology vs. rehabilitation department). Independent factors associated with CR quality were the availability of "professional CR providers" and staff perceptions of CR improving physician-patient relationships. The medical system factors did not affect the development and quality of CR, including hospital level, funding type, academic type, general/specialized hospital, located city, medical insurance, the existence of a CR outpatient clinic and independent space, the availability of professional CR providers, staff structure, and the availability of regular training and standard procedure. Conclusions: The development and quality of a phase II CR program may benefit from factors including support from administrators and resident physicians, adequately training more CR providers, without viewing medical system factors as a major issue.

2.
Hum Mutat ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33822436

RESUMO

One of the greatest challenges in human genetics is deciphering the link between functional variants in non-coding sequences and the pathophysiology of complex diseases. To address this issue, many methods have been developed to sort functional single nucleotide variants (SNVs) for neutral SNVs in non-coding regions. In this study, we integrated well-established features and commonly used datasets, and merged them into large-scale datasets based on a random forest model, which yielded promising performance and outperformed some cutting-edge approaches. Our analyses of feature importance and data coverage also provide certain clues for future research in enhancing the prediction of functional non-coding SNVs. This article is protected by copyright. All rights reserved.

3.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 202-206, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829692

RESUMO

Objective: To examine the infectivity of human adenovirus type 55 (HAdV-55) in human intestinal cells. Methods: Caco-2 cells were cultured in vitro, and infected with HAdV-3, 7, 14 and 55. The expression of viral proteins in infected cells was detected with immunofluorescence method. The intracellular and supernatant viral DNA levels were determined with fluorescent quantitative PCR at different points of time. The level of infectious virus particles in the supernatant of Caco-2 cells was determined with adenovirus sensitive HEp-2 infection assay. Results: Immunofluorescence assay showed positive result for the expression of HAdV-55 virus protein in Caco-2 cells 48 h post infection. HAdV-3, 7, 14, and 55 showed sustained replication and proliferation in Caco-2 cells. The level of viral DNA in infected cells and the supernatant increased with the infection time, and the viral DNA level of HAdV-55 was significantly higher than those of HAdV-3, 7 and 14. The infectious virus particles of HAdV-55 in Caco-2 supernatant were more than those of HAdV-3, 7 and 14, showing statistically significant difference ( P<0.05). Caco-2 cells were infected with low doses of virus (1×TCID 50), and the cytopathic effect (CPE) of HAdV-55 infection wells was more significant than that of HAdV-3, 7 and 14 infection wells. Conclusion: This study found that human intestinal cells were susceptible to HAdV-55, and the infection level was higher than that of other common respiratory infections caused by adenovirus types 3, 7 and 14.


Assuntos
Adenovírus Humanos , Adenoviridae/genética , Adenovírus Humanos/genética , Células CACO-2 , DNA Viral , Humanos , Replicação Viral
4.
Nucleic Acids Res ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836077

RESUMO

Lysine acetylation (Kac) is well known to occur in histones for chromatin function and epigenetic regulation. In addition to histones, Kac is also detected in a large number of proteins with diverse biological functions. However, Kac function and regulatory mechanism for most proteins are unclear. In this work, we studied mutation effects of rice genes encoding cytoplasm-localized histone deacetylases (HDAC) on protein acetylome and found that the HDAC protein HDA714 was a major deacetylase of the rice non-histone proteins including many ribosomal proteins (r-proteins) and translation factors that were extensively acetylated. HDA714 loss-of-function mutations increased Kac levels but reduced abundance of r-proteins. In vitro and in vivo experiments showed that HDA714 interacted with r-proteins and reduced their Kac. Substitutions of lysine by arginine (depleting Kac) in several r-proteins enhance, while mutations of lysine to glutamine (mimicking Kac) decrease their stability in transient expression system. Ribo-seq analysis revealed that the hda714 mutations resulted in increased ribosome stalling frequency. Collectively, the results uncover Kac as a functional posttranslational modification of r-proteins which is controlled by histone deacetylases, extending the role of Kac in gene expression to protein translational regulation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33844628

RESUMO

There is significant acoustic impedance contrast between the cortical bone and surrounding soft tissue, resulting in difficulty for ultrasound penetration into bone tissue with high frequency. It is challenging for the conventional pulse-echo modalities to give accurate cortical bone images using uniform sound velocity model. To overcome these limitations, an ultrasound imaging method called full-matrix Fourier-domain synthetic aperture based on velocity inversion (FM-FDSA-VI) was developed to provide accurate cortical bone images. The dual linear arrays were located on the upper and lower sides of the imaging region. After full-matrix acquisition with two identical linear array probes facing with each other, travel-time inversion was used to estimate the velocity distribution in advance. Then, full-matrix Fourier-domain synthetic aperture (FM-FDSA) imaging based on the estimated velocity model was applied twice to image the cortical bone, utilizing the data acquired from top and bottom linear array respectively. Finally, to further improve the image quality, the two images were merged to give the ultimate result. The performance of the method was verified by two simulated models and two bone phantoms (i.e., regularly and irregularly hollow bone phantom). The mean relative errors of estimated sound velocity in the region-of-interest (ROI) are all below 12%, and the mean errors of cortical section thickness are all less than 0.3 mm. Compared to the conventional synthetic aperture (SA) imaging, FM-FDSA-VI method is able to accurately image cortical bone with respect to the structure. Moreover, the result of irregular bone phantom was close to the image scanned by micro computed tomography (µCT) in terms of macro geometry and thickness. It is demonstrated that the proposed FM-FDSA-VI method is an efficient way for cortical bone ultrasonic imaging.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33846073

RESUMO

OBJECTIVE: This study aimed to determine the effect of intervention timing, from symptom onset to thoracic endovascular aortic repair (TEVAR), on early and late outcomes in high risk patients with uncomplicated type B aortic dissection (uTBAD). METHODS: The study retrospectively evaluated 267 uTBAD patients with high risk radiographic features who underwent pre-emptive TEVAR during the acute and subacute periods. Demographics, comorbidities, pre-operative imaging features, peri-procedural details, and follow up outcomes were analysed. RESULTS: Among the 267 pre-emptive TEVARs for high risk uTBAD, 130 were performed in the acute phase (1-14 days); and 137 in the subacute phase (15-90 days), from initial presentation. The mean age was 55.9 ± 11.0 years and 222 (83.1%) were men. The 30 day mortality rate in the acute group was five times higher than that in the subacute group (3.8% vs. 0.7%), although without statistically significant difference (p = .11). No statistically significant difference in 30 day outcomes (aortic rupture, retrograde type A dissection [RTAD], immediate type Ia endoleak, stroke, spinal cord ischaemia, and re-intervention) was noted (p > .05 for each). Of note, aortic rupture, RTAD, and disabling stroke were observed only in the acute group. Multivariable logistic analyses showed that intervention timing was not associated with 30 day outcomes. The median clinical follow up was 48.2 ± 25.9 months (range 1 - 106 months). There were no significant differences in all cause mortality, dissection related death, late intervention, or aortic related late events among timing cohorts (p > .05 for each). Furthermore, aortic remodelling, by analysing the flow status of the false lumen and evaluation of aortic diameters, either at the thoracic aorta level or the abdominal aorta level, was similar between the two groups. Multivariable Cox analyses showed that intervention timing was not associated with late outcomes. CONCLUSION: The present study indicates that TEVAR for high risk uTBAD in the acute phase was associated with a trend toward higher rates of early complications, while the long term outcomes were comparable with those of the subacute phase.

7.
J Environ Manage ; 288: 112450, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33823448

RESUMO

The fragility and high cost of enzymes represent critical challenges limiting their practical application in the removal of pesticides. Herein, an aryloxyphenoxypropionate herbicide-hydrolyzing enzyme, QpeH, was purified via one-step affinity chromatography and embedded into two types of zeolitic imidazolate frameworks (ZIFs) through biomimetic mineralization. The catalytic activity towards the herbicide quizalofop-P-ethyl, the loading capacity and efficiency of the resulting two composites, QpeH@ZIF-10 with cruciate flower-like morphology and QpeH@ZIF-8 with rhombic dodecahedral morphology, were compared. Both composites had excellent stability and reusability after 10 reuse cycles, with QpeH@ZIF-10 having a better performance. More importantly, when applied for the removal of quizalofop-P-ethyl pollution in the watermelon field, QpeH@ZIF-10 (88%) showed a remarkably improved degradation efficiency compared to QpeH@ZIF-8 (84%) despite the latter having a greater loading capacity. Finally, the use of QpeH@ZIF composites was shown to recover the bacterial community in soil. This work provides a new insight into the low-cost synthesis of nanobiocatalysts combining simple purified enzymes and metal-organic frameworks (MOFs) for the remediation of pesticide-contaminated soils.

8.
BMC Public Health ; 21(1): 699, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836703

RESUMO

BACKGROUND: Anaemia is prevalent in children. Therefore, this study examined the association between dietary patterns and anaemia among children in central South China. METHODS: Cross-sectional studies were conducted in Mayang, central South China, in 2015 and 2018. Diet data were collected using a questionnaire, and dietary patterns were identified via exploratory factor analysis. Haemoglobin was measured to assess anaemia status. Associations between dietary patterns and anaemia were assessed using a logistic regression model. RESULTS: The mean age of the infants surveyed was 14.06 months in 2015 and 16.58 months in 2018. Four dietary patterns were identified among infants aged 6-23 months: a diversified diet consisting mainly of tubers, dairy products, beans and bean products; a traditional diet consisting mainly of cereals, water, soup, vegetables and fruit; mainly breast milk, with a little powdered formula; or mainly multi-nutrient powders. The prevalence of anaemia in infants decreased from 29.49% in 2015 to 20.26% in 2018.In infants fed a diversified diet or multi-nutrient powders with top-quartile (Q4) scores, the risk of anaemia was reduced by 45%(adjusted odds ratio [AOR] = 0.55, 95%CI0.30-0.99, P = 0.047) or 59% (AOR = 0.41, 95% CI0.22-0.78, P = 0.006), respectively, compared to infants in the lowest quartile (Q1). Infants fed mainly breast milk had a 3.26-fold greater risk of anaemia compared to those with Q1 scores (AOR = 3.26, 95% CI 1.83-5.81, P < 0.001). CONCLUSIONS: Four dietary patterns were identified among infants aged 6-23 months in central South China. Infants should be fed a variety of food groups to improve their anaemia status.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33839040

RESUMO

BACKGROUND: Bladder-sparing chemoradiation therapy is a definitive first-line treatment option for muscle-invasive bladder cancer. Randomized trials have demonstrated that the addition of neoadjuvant chemotherapy to radical cystectomy or radiation monotherapy results in a survival benefit. Whether neoadjuvant chemotherapy improves outcomes when used with definitive chemoradiation is unknown. PATIENTS AND METHODS: We identified 2566 patients in the National Cancer Data Base with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with definitive intent concurrent chemoradiation from 2004 to 2015. The exposure of interest was receipt of neoadjuvant chemotherapy versus those without neoadjuvant chemotherapy. The primary outcome was overall survival defined from the time of diagnosis. Kaplan-Meier and multivariable Cox proportional hazard analyses were used to compare survival between groups. Sensitivity analyses tested (1) an interaction term for clinical T stage and (2) defining survival from start of radiation (as opposed to time of diagnosis) to address potential leading time bias. RESULTS: We identified 462 patients treated with neoadjuvant chemotherapy followed by chemoradiation and 2104 patients treated with chemoradiation alone. With a median follow-up of 6.2 years, we found no difference in survival between groups: 5-year or 10-year overall survival of 30.6% (95% confidence interval [CI], 28.4%-32.9%) in the neoadjuvant group versus 31.8% (95% CI, 27.0%-36.8%) in the standard chemoradiation therapy group and 13.3% (95% CI, 11.2%-15.5%) in the neoadjuvant group versus 13.0% (95% CI, 8.4%-18.7%) in the standard chemoradiation therapy group, respectively (log-rank P = .19). On multivariable analysis we found no association between receipt of neoadjuvant chemotherapy and overall survival (hazard ratio, 1.01; 95% CI, 0.88-1.15; P = .921). The sensitivity analyses did not identify any differential effect by clinical T stage nor by defining survival from start of radiation. CONCLUSION: These results do not support the routine addition of neoadjuvant chemotherapy to definitive chemoradiation for bladder cancer, and optimizing the chemotherapy sequencing and regimens for bladder-preserving approaches to muscle invasive bladder cancer should continue to be studied under prospective clinical trials.

10.
Curr Microbiol ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33813642

RESUMO

A Gram-stain-negative, yellow-pigmented, rod-shaped, strictly aerobic, non-motile bacterium, designated BDHS18T, was isolated from the sediment of the Hasuhai Lake, China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that this strain belongs to the genus Moheibacter in the family Flavobacteriaceae and its closest relative was Moheibacter sediminis JCM 19634T (96.0%), followed by Moheibacter stercoris DSM 29388T (95.3%). Cells of strain BDHS18T were catalase-positive and oxidase-negative. Strain BDHS18T was found to grow optimally at 28-33 â„ƒ, pH 7.5-8.0, and in the presence of approximately 1.0% (w/v) NaCl. Major cellular fatty acids were iso-C15:0, iso-C17:0 3-OH, Summed feature 4 and Summed feature 9. The predominant respiratory quinone was MK-6. The predominant polar lipids in strain BDHS18T were phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminolipid and one unidentified lipid. The DNA G + C content was 36.9 mol%. According to the phylogenetic analysis, physiological and phenotypic characteristics, strain BDHS18T represents a novel species of the genus Moheibacter, for which the name Moheibacter lacus sp. nov. is proposed. The type strain is BDHS18T (= KCTC 72160T = MCCC 1H00369T).

11.
J Integr Neurosci ; 20(1): 43-53, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33834690

RESUMO

The cingulo-opercular network (CON), dorsal attention network (DAN), and ventral attention network (VAN) are prominently activated during attention tasks. The function of these task-positive networks and their interplay mechanisms in attention is one of the central issues in understanding how the human brain manipulates attention to better adapt to the external environment. This study aimed to clarify the CON, DAN, and VAN's functional hierarchy by assessing causal interactions. Functional magnetic resonance imaging (fMRI) data from human participants performing a visual-spatial attention task and correlating Granger causal influences with behavioral performance revealed that CON exerts behavior-enhancing influences upon DAN and VAN, indicating a higher level of CON in top-down attention control. By contrast, the VAN exerts a behavior-degrading influence on CON, indicating external disruption of the CON's control set.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33835229

RESUMO

PURPOSE: This phase 1, open-label, single-arm clinical trial evaluated pharmacokinetics, safety, and biomarker activity of palbociclib-letrozole as first-line treatment for estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) in postmenopausal Chinese women to support palbociclib approval in China. METHODS: Patients received palbociclib 125 mg once daily (3/1 schedule) plus letrozole 2.5 mg once daily. Blood samples were collected predose and ≤ 120 h after single and multiple doses of palbociclib. The incidence and severity of adverse events were reported. Skin biopsy tissues and blood samples were collected for biomarker assessments. RESULTS: By 31 July 2018, 26 patients were enrolled. After single and multiple dosing, palbociclib maximum plasma concentration was 82.14 and 139.7 ng/mL, apparent clearance was 52.40 and 49.97 L/h, AUCτ was 1217 and 2501 ng∙h/mL, and t½ was 23.46 and 27.26 h, respectively. Levels of Ki67, retinoblastoma protein, and thymidine kinase decreased after palbociclib treatment. A similar safety profile as previously reported was observed. CONCLUSIONS: Pharmacokinetic and pharmacodynamic effects of palbociclib were well characterized in Chinese patients with ABC. Despite higher exposure, pharmacokinetic parameters were similar to those of a previously studied non-Asian population. No palbociclib dose adjustment based on Chinese ethnicity is needed. Palbociclib-letrozole had a manageable safety profile. CLINICAL TRIAL REGISTRATION: NCT02499146.

13.
J Phys Chem A ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797906

RESUMO

Valence-bound anions with a dipolar core can support dipole-bound states (DBSs) below the electron detachment threshold. The highly diffuse DBS observed is usually of σ symmetry with an s-like orbital. Recently, a π-type DBS was observed experimentally in the 9-anthrolate anion (9AT-) and it was shown to be stabilized due to the large anisotropic polarizability of the 9AT core. To confirm the general existence of π-DBS and its structural dependence, here we report an investigation of the 9-phenanthrolate anion (9PT-), which has a different structure and lower symmetry than 9AT-. Photodetachment spectroscopy revealed a DBS 257 cm-1 below the detachment threshold of 9PT- at 19 627 cm-1 (2.4334 eV). Resonant two-photon photoelectron imaging indeed showed a π symmetry for the DBS. Similar to that observed in 9AT-, the π-DBS in 9PT- is also stabilized by the anisotropic polarizability of the 9PT core and accessed via nonadiabatic population transfer from the initially populated σ-DBS. Photodetachment spectroscopy unveiled nine above-threshold vibrational resonances of the DBS, resulting in nine highly non-Franck-Condon resonant photoelectron spectra by tuning the detachment laser to the vibrational resonances. The combination of photodetachment spectroscopy and resonant photoelectron spectroscopy allowed frequencies for nine vibrational modes of the 9-phenathroxy radical to be measured, including the six lowest frequency bending modes.

14.
Pharmaceutics ; 13(4)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804947

RESUMO

The emergence and prevalence of multidrug-resistant (MDR) bacteria have posed a serious threat to public health. Of particular concern are methicillin-resistant Staphylococcus aureus (MRSA) and blaNDM, mcr-1 and tet(X)-positive Gram-negative pathogens. The fact that few new antibiotics have been approved in recent years exacerbates this global crisis, thus, new alternatives are urgently needed. Antimicrobial peptides (AMPs) originated from host defense peptides with a wide range of sources and multiple functions, are less prone to achieve resistance. All these characteristics laid the foundation for AMPs to become potential antibiotic candidates. In this study, we revealed that peptide WW307 displayed potent antibacterial and bactericidal activity against MDR bacteria, including MRSA and Gram-negative bacteria carrying blaNDM-5, mcr-1 or tet(X4). In addition, WW307 exhibited great biofilm inhibition and eradication activity. Safety and stability experiments showed that WW307 had a strong resistance against various physiological conditions and displayed relatively low toxicity. Mechanistic experiments showed that WW307 resulted in membrane damage by selectively targeting bacterial membrane-specific components, including lipopolysaccharide (LPS), phosphatidylglycerol (PG), and cardiolipin (CL). Moreover, WW307 dissipated membrane potential and triggered the production of reactive oxygen species (ROS). Collectively, these results demonstrated that WW307 represents a promising candidate for combating MDR pathogens.

15.
J Ultrasound Med ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792978

RESUMO

OBJECTIVES: This study aimed to screen the significant sonographic features for differentiation of benign and malignant superficial lymph nodes (LNs) by logistic regression analysis and fit a model to diagnose LNs. METHODS: A total of 204 pathological LNs were analyzed retrospectively. All the LNs underwent conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) examinations. A total of 16 suspicious sonographic features were used to assess LNs. All variables that were statistically related to the diagnosis of LNs were included in the logistic regression analysis in order to ascertain the significant features of diagnosing LNs, and to establish a logistic regression analysis model. RESULTS: The significant features in the logistic regression analysis model of diagnosing malignant LNs were absence of echogenic hilus, age, and absence of hilum after enhancement. According to the results of logistic regression analysis, the formula to predict whether LNs were malignant was established. The area under the receiver operating curve (ROC) was 0.908 and the accuracy, sensitivity, and specificity were 85.0%, 92.9%, and 85.3%, respectively. CONCLUSION: The logistic regression model for the significant sonographic features of conventional US and CEUS is an effective and accurate diagnostic tool for differentiating malignant and benign LNs.

16.
J Dig Dis ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33793080

RESUMO

AIM: To identify whether bile reflux on endoscopy and other related variables are risk factors for precancerous gastric lesions and gastric cancer. METHODS: A multi-centre, cross-sectional and observational study was conducted in five centres from June to October 2019, and a total of 1162 patients were recruited and divided into three groups: (1) chronic gastritis group; (2) precancerous lesions group (low-grade intraepithelial neoplasia and gastric intestinal metaplasia); and (3) gastric cancer group. All participants underwent detailed interviews and endoscopic gastric biopsies and completed questionnaires. Odds ratios (ORs) for factors were calculated by multivariate logistic regression models with or without adjustment for H. pylori infection. RESULTS: We recruited 668 patients with chronic gastritis, 411 patients with precancerous lesions and 83 patients with gastric cancer. Through comparisons between the chronic gastritis and precancerous lesion groups, grade of bile reflux, age, sex, some dietary habits and family history of gastric cancer were confirmed as independent risk factors for cancerous gastric lesions. Similar results were obtained when comparing the chronic gastritis group with the gastric cancer group. In addition, bile reflux was confirmed as an independent risk factor for the progression from precancerous lesions to cancer. CONCLUSIONS: This study confirmed bile reflux on endoscopy as well as age, some dietary habits and family history of gastric cancer as independent risk factors for the occurrence of precancerous gastric lesions and gastric cancer.

17.
Bioresour Technol ; 329: 124927, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33706177

RESUMO

The anaerobic digestion of leachate from organic fraction of municipal solid waste (OFMSW) is a long-standing challenge. A submerged anaerobic membrane bioreactor (AnMBR) embedding three flat sheet membrane was therefore continuously operated for 63 days to investigate the materials flow and membrane performance. The results obtained show that approximately 90% COD was removed and 86% was converted into methane under an OLR of 5.6 kgCOD/m3·d corresponding to a HRT of 10 days. Under the high solid condition (34.5-61.1 g/L total solids in AnMBR) and flux of 5 and 6 LMH, the membranes was operated practically at constant trans-membrane pressure (TMP). When the membrane was operated at a high flux of 7 LMH the TMP rapid increase occurred in 22 h resulting in a non-recoverable permeability. A sustainable flux was thus identified. This study demonstrated the feasibility of AnMBR treating OFMSW leachate under high solid condition with high flux.


Assuntos
Membranas Artificiais , Resíduos Sólidos , Anaerobiose , Reatores Biológicos , Metano , Eliminação de Resíduos Líquidos
18.
JAMA Surg ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33787826

RESUMO

Importance: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension but remains largely unrecognized and untreated. Objective: To understand the outcomes of a specialized clinic on rates of evaluation and treatment of PA in the context of secondary factors. Design, Setting, and Participants: This population-based cohort study was conducted in Alberta, Canada, using linked administrative data between April 1, 2012, and July 31, 2019, on adults identified as having hypertension. Main Outcomes and Measures: We evaluated each step of the diagnostic and care pathway for PA to determine the proportion of people with hypertension who received screening, subtyping, and targeted treatment for PA. Variations in diagnosis and treatment were examined according to individual-level, clinician-level, and system-level characteristics. Results: Of the 1.1 million adults with hypertension, 7941 people (0.7%) were screened for PA. Among those who were screened, 1703 (21.4%) had positive test results consistent with possible PA, and 1005 (59.0%) of these were further investigated to distinguish between unilateral and bilateral forms of PA. Only 731 individuals (42.9%) with a positive screen result received disease-targeted treatment. Geographic zones and clinician specialty were the strongest determinants of screening, subtyping, and treatment of PA, with the highest rates corresponding to the location of the provincial endocrine hypertension program. Conclusions and Relevance: In this cohort, less than 1% of patients expected to have PA were ever formally diagnosed and treated. These findings suggest that a system-level approach to assist with investigation and treatment of PA may be highly effective in closing care gaps and improving clinical outcomes.

19.
Life Sci ; 273: 119314, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667513

RESUMO

AIM: To emphasize the mechanism of the effect of exercise on lipid droplet (LD) metabolism disorder in nonalcoholic fatty liver disease (NAFLD). MAIN METHODS: C57BL/6J mice were randomly divided into three groups: The first group was fed with a normal diet (CON), the second group was fed a high-fat diet (HF), and finally group with a high-fat diet intervention and swim training (HF-EX). The total intervention period was 16 weeks. RT-PCR and Western blot were performed to evaluate the effect of exercise on LDs metabolism and the AMPK pathway. Histopathological examinations and immunofluorescence were performed to evaluate the lipid deposition and lipophagy in the liver. KEY FINDINGS: Exercise reduced liver steatosis and insulin resistance along with the stimulation of AMPK/SIRT1 signaling and downstream regulation of lipid metabolism. In addition, exercise increased the expression of autophagy marker and colocalization of LC3 and LAMP1 with LDs. SIGNIFICANCE: Exercise stimulated AMPK/SIRT1 and activated lipophagy in NAFLD. Enhancing lipophagy may be one of the key mechanisms of regulation and resolution of NAFLD by exercise.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Dieta Hiperlipídica/efeitos adversos , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Condicionamento Físico Animal , Proteínas Quinases Ativadas por AMP/genética , Animais , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia
20.
Theranostics ; 11(10): 4894-4909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754034

RESUMO

IL-4 induces Akt activation in macrophages, required for full M2 (alternative) polarization. We examined the roles of Gαi1 and Gαi3 in M2 polarization using multiple genetic methods. Methods and Results: In MEFs and primary murine BMDMs, Gαi1/3 shRNA, knockout or dominant negative mutations attenuated IL-4-induced IL4Rα endocytosis, Gab1 recruitment as well as Akt activation, leaving STAT6 signaling unaffected. Following IL-4 stimulation, Gαi1/3 proteins associated with the intracellular domain of IL-4Rα and the APPL1 adaptor, to mediate IL-4Rα endosomal traffic and Gab1-Akt activation in BMDMs. In contrast, gene silencing of Gαi1/3 with shRNA or knockout resulted in BMDMs that were refractory to IL-4-induced M2 polarization. Conversely, Gαi1/3-overexpressed BMDMs displayed preferred M2 response with IL-4 stimulation. In primary human macrophages IL-4-induced Akt activation and Th2 genes expression were inhibited with Gαi1/3 silencing, but augmented with Gαi1/3 overexpression. In Gαi1/3 double knockout (DKO) mice, M2 polarization, by injection of IL-4 complex or chitin, was potently inhibited. Moreover, in a murine model of asthma, ovalbumin-induced airway inflammation and hyperresponsiveness were largely impaired in Gαi1/3 DKO mice. Conclusion: These findings highlight novel and essential roles for Gαi1/3 in regulating IL-4-induced signaling, macrophage M2 polarization and allergic asthma response.

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