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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Lin, Zhen, et al.
(författare)
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Worse Outcomes After Readmission to a Different Hospital After Sepsis : A Nationwide Cohort Study
- 2022
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Ingår i: Journal of Emergency Medicine. - : Elsevier. - 0736-4679 .- 1090-1280. ; 63:4, s. 569-581
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the United States, sepsis accounts for 13% of the total hospital expenses and > 50% of hospital deaths. Moreover, people with sepsis are more likely to be readmitted.OBJECTIVE: The aim of this study was to assess the prevalence and outcomes of different hospital readmissions (DHRs) in patients with sepsis, and the factors associated with DHR.METHODS: We used data from the Nationwide Readmissions Database of the United States in 2017 to identify patients admitted for sepsis. Multivariable logistic regression analysis was used to evaluate the factors associated with DHR; five models were constructed to elucidate the relationship between DHR and in-hospital outcomes.RESULTS: In 2017, 85,120 (21.97%) of all patients with sepsis readmitted within 30 days in the United States were readmitted to a different hospital. The most common reason for readmission was infection irrespective of hospital status. Compared with the patients with sepsis who were readmitted to the same hospital, DHR was associated with higher hospitalization costs ($2264; 95% CI $1755-$2772; p < 0.001), longer length of stay (0.58 days; 95% CI 0.44-0.71 days; p < 0.001), and higher risk of in-hospital mortality (odds ratio 1.63; 95% CI 1.55-1.72; p < 0.001).CONCLUSIONS: DHR occurred in one-fifth of patients with sepsis in the United States. Our findings suggest that patients readmitted to a different hospital within 30 days may experience higher in-hospital mortality, longer length of stay, and higher hospitalization costs. Future studies need to examine whether continuity of care can improve the prognosis of patients with sepsis.
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| 8. |
- Wu, Jia-Jia, et al.
(författare)
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Late-life depression and the risk of dementia in 14 countries : a 10-year follow-up study from the Survey of Health, Ageing and Retirement in Europe
- 2020
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 274, s. 671-677
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Tidskriftsartikel (refereegranskat)abstract
- Background: Depression is the most common mental health problem and often co-occurs with dementia in old age. This study investigates the in fluence of late-life depression on risk of dementia.Methods: A total of 16210 dementia-free participants aged 60+ from the Survey of Health, Aging, and Retirement in Europe were followed up for 10 years to detect incident dementia. Depression was assessed by a 12-item Europe-depression scale, dementia was determined by physician diagnosis reported by the participants and their informants. Fine and Gray model was performed to explore the association between depression and incident dementia taking into account competing risk of death.Results: During an average of 8 years follow-up, 1030 (6.35%) incident dementia were identi fied. Late-life depression was related to higher subdistribution hazard ratio (sHR) of dementia (sHR=1.52, 95%CI: 1.32-1.75) after adjusting for age, gender, country, education, smoking, drinking, living arrangement, BMI, chronic disease, and physical activity. Further, the risk was only existed in those below age of 80 (sHR=1.75, 95%CI: 1.47-2.07). In addition, a dose-response association was observed between the severity of depression and dementia risk (p for trend<0.001).Limitation: The ascertainment of depression and dementia was based on information reported by the participants and/or their informants, which might result in information bias. The causal relationship could not be determined because limited follow-up time.Conclusions: Late-life depression is associated with higher incidence of dementia in a dose-response fashion. Interventions targeting depression patients aged 60-79 years and those with severe depression may be e ffective strategies to prevent dementia.
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| 9. |
- Wu, Jia-Zhen, et al.
(författare)
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Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy
- 2019
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Ingår i: Translational Neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progressive accumulation of α-synuclein is a key step in the pathological development of Parkinson's disease. Impaired protein degradation and increased levels of α-synuclein may trigger a pathological aggregation in vitro and in vivo. The chaperone-mediated autophagy (CMA) pathway is involved in the intracellular degradation processes of α-synuclein. Dysfunction of the CMA pathway impairs α-synuclein degradation and causes cytotoxicity.Results: In the present study, we investigated the effects on the CMA pathway and α-synuclein aggregation using bioactive ingredients (Dihydromyricetin (DHM) and Salvianolic acid B (Sal B)) extracted from natural medicinal plants. In both cell-free and cellular models of α-synuclein aggregation, after administration of DHM and Sal B, we observed significant inhibition of α-synuclein accumulation and aggregation. Cells were co-transfected with a C-terminal modified α-synuclein (SynT) and synphilin-1, and then treated with DHM (10 μM) and Sal B (50 μM) 16 hours after transfection; levels of α-synuclein aggregation decreased significantly (68% for DHM and 75% for Sal B). Concomitantly, we detected increased levels of LAMP-1 (a marker of lysosomal homeostasis) and LAMP-2A (a key marker of CMA). Immunofluorescence analyses showed increased colocalization between LAMP-1 and LAMP-2A with α-synuclein inclusions after treatment with DHM and Sal B. We also found increased levels of LAMP-1 and LAMP-2A both in vitro and in vivo, along with decreased levels of α-synuclein. Moreover, DHM and Sal B treatments exhibited anti-inflammatory activities, preventing astroglia- and microglia-mediated neuroinflammation in BAC-α-syn-GFP transgenic mice.Conclusions: Our data indicate that DHM and Sal B are effective in modulating α-synuclein accumulation and aggregate formation and augmenting activation of CMA, holding potential for the treatment of Parkinson's disease.
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| 10. |
- Han, Hedong, et al.
(författare)
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Prevalence, trends, and outcomes of atrial fibrillation in hospitalized patients with metastatic cancer : findings from a national sample
- 2021
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 10:16, s. 5661-5670
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological evidence regarding the link between cancer and atrial fibrillation (AF) are limited and outcomes of metastatic cancer comorbid with AF need to be elucidated.Objective: This study aims to evaluate the prevalence, temporal trends, and outcomes of AF in hospitalized metastatic cancer patients.Methods: The National Inpatient Sample (NIS) database was used to identify adult patients with metastatic tumors from 2003 to 2014. We analyzed the trends in AF prevalence, in-hospital mortality, total cost, length of stay (LOS), and comorbidities pertaining to metastatic cancer. Multivariable-adjusted models were used to evaluate the association of AF with clinical factors, in-hospital mortality, total cost, and LOS.Results: Among 2,478,598 patients with metastatic cancer, 8.74% (216,737) were diagnosed with AF. The proportion of comorbid AF increased from 8.28% in 2003 to 10.06% in 2014 (p < 0.0001). Older age, white race, male, Medicare, higher income, larger hospital bed size, and urban teaching hospital were associated with higher AF occurrence. Among primary tumor sites, lung cancer experienced the highest odds of AF compared to other cancers. Patients with metastasis to lymph node and respiratory organ had higher odds of AF. In metastatic cancer, AF was associated with higher in-hospital mortality (odds ratio: 1.48; 95% confidence interval: 1.43-1.54), 18% longer LOS, and 19% higher cost.Conclusions: AF prevalence in metastatic cancer continues to increase from 2003 to 2014. AF is linked to poorer prognosis and higher healthcare resource utilization. As the population ages, optimal preventive and treatment management strategies are needed for metastatic cancer comorbid with AF.
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| 11. |
- Lin, Zhen, et al.
(författare)
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Discharge Against Medical Advice in Acute Ischemic Stroke : the Risk of 30-Day Unplanned Readmission
- 2021
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Ingår i: Journal of general internal medicine. - : Springer. - 0884-8734 .- 1525-1497. ; 36:5, s. 1206-1213
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Discharge against medical advice may be associated with more readmissions.OBJECTIVE: To evaluate DAMA in patients with acute ischemic stroke (AIS) and identify the relationship between DAMA and 30-day unplanned readmissions.DESIGN: A retrospective cohort study.PARTICIPANTS: The National Readmission Database was used to identify inpatients with a primary diagnosis of AIS who were either discharged home or DAMA between 2010 and 2017 in the USA.MEASURES: Demographic features, hospital type, comorbidities, stroke risk factors, severity indices, and treatments were compared between patients discharged routinely and DAMA. Multivariable logistic regression was used to evaluate predictors of DAMA, and a double robust inverse probability of treatment weighting method was used to assess the association between DAMA and 30-day unplanned readmissions.KEY RESULTS: Overall, 1,335,484 patients with AIS were included, of whom 2.09% (n = 27,892) were DAMA. The prevalence of DAMA in AIS patients increased from 1.65 in 2010 to 2.57% in 2017. The rates of 30-day unplanned readmissions for DAMA and non-DAMA patients were 16.81% and 7.78%, respectively. Patients with drug abuse, alcohol abuse, smoking, prior stroke, psychoses, and intravenous thrombolysis had greater odds of DAMA. DAMA was associated with all-cause readmissions (OR, 2.04; 95% CI, 2.01-2.07) and remained a strong predictor for transient ischemic attack/stroke-specific and cardiac-specific causes of readmissions.CONCLUSIONS: Although the DAMA rate is low in AIS patients, DAMA is a risk factor for all-cause and recurrent stroke-specific readmissions. Future studies are needed to address issues around compliance and engagement with health care to reduce DAMA.
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| 12. |
- Lin, Zhen, et al.
(författare)
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Outcomes after readmission at the index or nonindex hospital following acute myocardial infarction complicated by cardiogenic shock
- 2021
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Ingår i: Clinical Cardiology. - : John Wiley & Sons. - 0160-9289 .- 1932-8737. ; 44:2, s. 200-209
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the prevalence and outcomes of readmission to nonindex hospitals after an admission for acute myocardial infarction complicated by cardiogenic shock (AMI-CS). We aimed to determine the rate of nonindex readmissions following AMI-CS and to evaluate its association with clinical factors, hospitalization cost, length of stay (LOS), and in-hospital mortality rates.HYPOTHESIS: Nonindex readmission may lead to worse in-hospital outcomes.METHODS: We reviewed the data of inpatients with AMI-CS between 2010 and 2017 using the National Readmission Database. The survey analytical methods recommended by the Healthcare Cost and Utilization Project were used for national estimates. Multiple regression models were used to evaluate the predictors of nonindex readmission, and its association with hospitalization cost, LOS, and in-hospital mortality rates.RESULTS: Of 238 349 patients with AMI-CS, 28028 (11.76%) had an unplanned readmission within 30 days. Of these patients, 7423 (26.48%) were readmitted to nonindex hospitals. Compared with index readmission, nonindex readmission was associated with higher hospitalization costs (p < .0001), longer LOS (p < .0001), and increased in-hospital mortality rates (p = .0016). Patients who had a history of percutaneous coronary intervention, received intubation/mechanical ventilation, or left against medical advice during the initial admission had greater odds of a nonindex readmission.CONCLUSIONS: Over one-fourth of readmissions following AMI-CS were to nonindex hospitals. These admissions were associated with higher hospitalization costs, longer LOS, and higher in-hospital mortality rates. Further studies are needed to evaluate whether a continuity of care plan in the acute hospital setting can improve outcomes after AMI-CS.
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| 13. |
- Ma, Tao, et al.
(författare)
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Genomic insights into salt adaptation in a desert poplar
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2797-
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Tidskriftsartikel (refereegranskat)abstract
- Despite the high economic and ecological importance of forests, our knowledge of the genomic evolution of trees under salt stress remains very limited. Here we report the genome sequence of the desert poplar, Populus euphratica, which exhibits high tolerance to salt stress. Its genome is very similar and collinear to that of the closely related mesophytic congener, P. trichocarpa. However, we find that several gene families likely to be involved in tolerance to salt stress contain significantly more gene copies within the P. euphratica lineage. Furthermore, genes showing evidence of positive selection are significantly enriched in functional categories related to salt stress. Some of these genes, and others within the same categories, are significantly upregulated under salt stress relative to their expression in another salt-sensitive poplar. Our results provide an important background for understanding tree adaptation to salt stress and facilitating the genetic improvement of cultivated poplars for saline soils.
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| 14. |
- Moser, Debra K., et al.
(författare)
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Identification of symptom clusters among patients with heart failure: An international observational study
- 2014
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Ingår i: International Journal of Nursing Studies. - : Elsevier. - 0020-7489 .- 1873-491X. ; 51:10, s. 1366-1372
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Tidskriftsartikel (refereegranskat)abstract
- Background: Virtually all patients with heart failure experience multiple symptoms simultaneously, yet clinicians and researchers usually consider symptoms in isolation. Recognizing and responding early to escalating symptoms is essential to preventing hospitalizations in heart failure, yet patients have considerable difficulty recognizing symptoms. Identification of symptom clusters could improve symptom recognition, but cultural differences may be present that must be considered. Objectives: To identify and compare symptom clusters in heart failure patients from the United States, Europe and Asia. Design: Cross-sectional, observational study. Settings: In- and out-patient settings in three regions of the world: Asia (i.e., China and Taiwan); Europe (i.e., the Netherlands and Sweden); and the United States. Participants: A total of 720 patients with confirmed heart failure. Propensity scoring using New York Heart Association Classification was used to match participants from each of the three regions. Methods: Symptoms were identified using the Minnesota Living with Heart Failure Questionnaire. To identify symptom clusters we used cluster analysis with the hierarchical cluster agglomerative approach. We used the Euclidean distance to measure the similarity of variables. Proximity between groups of variables was measured using Wards method. The resulting clusters were displayed with dendrograms, which show the proximity of variables to each other on the basis of semi-partial R-squared scores. Results: There was a core group of symptoms that formed two comparable clusters across the countries. Dyspnea, difficulty in walking or climbing, fatigue/increased need to rest, and fatigue/low energy were grouped into a cluster, which was labeled as a physical capacity symptom cluster. Worrying, feeling depressed, and cognitive problems were grouped into a cluster, which was labeled as an emotional/cognitive symptom cluster. The symptoms of edema and trouble sleeping were variable among the countries and fell into different clusters. Conclusion: Despite the diversity in cultures studied, we found that symptoms clustered similarly among the cultural groups. Identification of similar symptoms clusters among patients with heart failure may improve symptom recognition in both patients and healthcare providers.
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| 15. |
- Song, Zhengyang, et al.
(författare)
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Mechanical Responses of a Deeply Buried Granite Exposed to Multilevel Uniaxial and Triaxial Cyclic Stresses : Insights into Deformation Behavior, Energy Dissipation, and Hysteresis
- 2021
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Ingår i: Advances in Materials Science and Engineering. - : Hindawi Publishing Corporation. - 1687-8434 .- 1687-8442. ; 2021
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Tidskriftsartikel (refereegranskat)abstract
- This article presents the results for cyclic uni/triaxial tests on the deeply seated granite samples drilled from a -915m deep tunnel in Sanshandao (SSD) gold mine. The monotonic and cyclic tests were carried out to observe the mechanical responses of the granite samples under different loading regimes. The disparities concerning the strain evolution and compressive strength of granite samples considering monotonic and cyclic uniaxial and triaxial loading are presented. Deformation behaviour, dissipated energy, and hysteresis are documented and evaluated. Quantitative correlations between strain evolution and cyclic stress levels are revealed. The amount of energy transformation during uniaxial and triaxial cyclic loading is determined. The impacts of confining pressure level on ultimate strain, energy dissipation, and stress-strain phase shift are presented. The mechanical responses of the granite samples subjected to different stress paths and loading strategies are summarised, and corresponding interpretations are given to clarify the differences of mechanical behaviour encountered in distinct loading methods.
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| 16. |
- Tse, Yi-Kei, et al.
(författare)
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Morphological and functional types of tricuspid regurgitation : prognostic value in patients undergoing tricuspid annuloplasty during left-sided valvular surgery
- 2023
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Ingår i: Clinical Research in Cardiology. - : Springer. - 1861-0684 .- 1861-0692. ; 112:10, s. 1463-1474
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Tidskriftsartikel (refereegranskat)abstract
- Background The nonuniform benefit of tricuspid annuloplasty may be explained by the proportionality of tricuspid regurgitation (TR) severity to right ventricular (RV) area. The purpose of this study was to delineate distinct morphological phenotypes of functional TR and investigate their prognostic implications in patients undergoing tricuspid annuloplasty during left-sided valvular surgery. Methods The ratios of pre-procedural effective regurgitant orifice area (EROA) with right ventricular end-diastolic area ( RVDA) were retrospectively assessed in 290 patients undergoing tricuspid annuloplasty. Based on optimal thresholds derived from penalized splines and maximally selected rank statistics, patients were stratified into proportionate (EROA/RVDA ratio <= 1.74) and disproportionate TR (EROA/RVDA ratio > 1.74). Results Overall, 59 (20%) and 231 (80%) patients had proportionate and disproportionate TR, respectively. Compared to those with proportionate TR, patients with disproportionate TR were older, had a higher prevalence of atrial fibrillation, lower pulmonary pressures, more impaired RV function, and larger tricuspid leaflet tenting area. Over a median follow-up of 4.1 years, 79 adverse events (47 heart failure hospitalizations and 32 deaths) occurred. Patients with disproportionate TR had higher rates of adverse events than those with proportionate TR (32% vs 10%; P = 0.001) and were independently associated with poor outcomes on multivariate analysis. TR proportionality outperformed guideline-based classification of TR severity in outcome prediction and provided incremental prognostic value to both the EuroSCORE II and STS score (incremental chi(2) = 6.757 and 9.094 respectively; both P < 0.05). Conclusions Disproportionate TR is strongly associated with adverse prognosis and may aid patient selection and risk stratification for tricuspid annuloplasty with left-sided valvular surgery.
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