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- 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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- Shepherd, L., et al.
(författare)
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Infection-related and -unrelated malignancies, HIV and the aging population
- 2016
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 17:8, s. 590-600
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.
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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
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- Neesgaard, B, et al.
(författare)
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How to RESPOND to Modern Challenges for People Living with HIV: A Profile for a New Cohort Consortium
- 2020
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Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: the International Cohort Consortium of Infectious Disease (RESPOND) is a collaboration dedicated to research on HIV and other infectious diseases. Methods: RESPOND is a flexible organization, with several independent substudies operating under one shared governance. HIV-related variables, including full antiretroviral therapy (ART) history, are collected annually for all participants and merged with substudy specific data into a shared data pool. Incident clinical events are reported using standardized forms. Prospective follow-up started 1/10/17 (enrolment) with retrospective data collected back to 01/01/12. Results: Overall, 17 cohorts from Europe and Australia provided data on 26,258 people living with HIV (PLWH). The majority (43.3%) of the population were white, with men-sex-with-men accounting for 43.3% of the risk for HIV acquisition. The median age was 48 years (IQR 40–56) and 5.2% and 25.5% were known to be co-infected with hepatitis B or C. While 5.3% were ART-naïve, the median duration on ART was 10.1 years (4.8–17.6), with 89.5% having a VL <200 copies/mL and the median CD4 count being 621 cells/µL (438–830). Malignancies (n = 361) and cardiovascular disease (n = 168) were the predominant reported clinical events. Conclusion: RESPOND’s large, diverse study population and standardized clinical endpoints puts the consortium in a unique position to respond to the diverse modern challenges for PLWH.
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- Gaboardi, M, et al.
(författare)
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Goals and Principles of Providers Working with People Experiencing Homelessness: A Comparison Between Housing First and Traditional Staircase Services in Eight European Countries
- 2019
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 16:9
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Tidskriftsartikel (refereegranskat)abstract
- The implementation and adaptation of the Housing First (HF) model represented profound changes the structure and delivery, goals, and principles of homeless services. These features of homeless services directly influence providers, their work performance and the clients’ outcomes. The present research, conducted in eight European countries, investigated how social providers working in HF or TS (Traditional Staircase) describe and conceptualize the goals and the principles of their services. Data were collected through 29 focus group discussions involving 121 providers. The results showed that HF and TS had similar and different goals for their clients in the following areas: support, social integration, satisfaction of needs, housing, and well-being. HF providers emphasized clients’ autonomy and ability to determine their personal goals, with housing being considered a start on the path of recovery, while TS were more focused on individual clients’ basic needs with respect to food, health and finding temporary accommodations. HF providers privileged the person-centered approach and housing as a right, while TS providers were more focused on helping everyone. Implications of the results are discussed as suggestions both for practice and for research.
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- Taylor, O, et al.
(författare)
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Lifetime, 5-year and past-year prevalence of homelessness in Europe: a cross-national survey in eight European nations
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:11, s. e033237-
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Tidskriftsartikel (refereegranskat)abstract
- To examine the lifetime, 5-year and past-year prevalence of homelessness among European citizens in eight European nations.DesignA nationally representative telephone survey using trained bilingual interviewers and computer-assisted telephone interview software.SettingThe study was conducted in France, Ireland, Italy, the Netherlands, Poland, Portugal, Spain and Sweden.ParticipantsEuropean adult citizens, selected from opt-in panels from March to December 2017. Total desired sample size was 5600, with 700 per country. Expected response rates of approximately 30% led to initial sample sizes of 2500 per country.Main outcome measuresHistory of homelessness was assessed for lifetime, past 5 years and past year. Sociodemographic data were collected to assess correlates of homelessness prevalence using generalised linear models for clustered and weighted samples.ResultsResponse rates ranged from 30.4% to 33.5% (n=5631). Homelessness prevalence was 4.96% for lifetime (95% CI 4.39% to 5.59%), 1.92% in the past 5 years (95% CI 1.57% to 2.33%) and 0.71% for the past year (95% CI 0.51% to 0.98%) and varied significantly between countries (pairwise comparison difference test, p<0.0001). Time spent homeless ranged between less than a week (21%) and more than a year (18%), with high contrasts between countries (p<0.0001). Male gender, age 45–54, lower secondary education, single status, unemployment and an urban environment were all independently strongly associated with lifetime homelessness (all OR >1.5).ConclusionsThe prevalence of homelessness among the surveyed nations is significantly higher than might be expected from point-in-time and homeless service use statistics. There was substantial variation in estimated prevalence across the eight nations. Coupled with the well-established health impacts of homelessness, medical professionals need to be aware of the increased health risks of those with experience of homelessness. These findings support policies aiming to improve health services for people exposed to homelessness.
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- Arvidsson-Lenner, R, et al.
(författare)
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Glycaemic index
- 2004
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Ingår i: Scandinavian Journal of Food and Nutrition. - : Informa UK Limited. - 1748-2976. ; 48:2, s. 84-94
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Tidskriftsartikel (refereegranskat)abstract
- The glycaemic index (GI) concept is based on the difference in blood glucose response after ingestion of the same amount of carbohydrates from different foods, and possible implications of these differences for health, performance and well-being. GI is defined as the incremental blood glucose area (0-2 h) following ingestion of 50 g of available carbohydrates in the test product as a percentage of the corresponding area following an equivalent amount of carbohydrate from a reference product. A high GI is generally accompanied by a high insulin response. The glycaemic load (GL) is the GI×the amount (g) of carbohydrate in the food/100. Many factors affect the GI of foods, and GI values in published tables are indicative only, and cannot be applied directly to individual foods. Properly determined GI values for individual foods have been used successfully to predict the glycaemic response of a meal, while table values have not. An internationally recognised method for GI determination is available, and work is in progress to improve inter- and intra-laboratory performance. Some epidemiological studies and intervention studies indicate that low GI diets may favourably influence the risk of chronic diseases such as diabetes and coronary heart disease, although further well-controlled studies are needed for more definite conclusions. Low GI diets have been demonstrated to improve the blood glucose control, LDL-cholesterol and a risk factor for thrombosis in intervention studies with diabetes patients, but the effect in free-living conditions remains to be shown. The impact of GI in weight reduction and maintenance as well as exercise performance also needs further investigation. The GI concept should be applied only to foods providing at least 15 g and preferably 20 g of available carbohydrates per normal serving, and comparisons should be kept within the same food group. For healthy people, the significance of GI is still unclear and general labelling is therefore not recommended. If introduced, labelling should be product-specific and considered on a case-by-case basis.
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- Sloth, B, et al.
(författare)
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No difference in body weight decrease between a low-glycemic-index and a high-glycemic-index diet but reduced LDL cholesterol after 10-wk ad libitum intake of the low-glycemic-index diet
- 2004
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Ingår i: American Journal of Clinical Nutrition. - 1938-3207. ; 80:2, s. 337-347
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of glycemic index (GI) in appetite and body-weight regulation is still not clear. Objective: The objective of the study was to investigate the long-term effects of a low-fat, high-carbohydrate diet with either low glycemic index (LGI) or high glycemic index (HGI) on ad libitum energy intake, body weight, and composition, as well as on risk factors for type 2 diabetes and ischemic heart disease in overweight healthy subjects. Design: The study was a 10-wk parallel, randomized, intervention trial with 2 matched groups. The LGI or HGI test foods, given as replacements for the subjects’ usual carbohydrate-rich foods, were equal in total energy, energy density, dietary fiber, and macronutrient composition. Subjects were 45 (LGI diet: n = 23; HGI diet: n = 22) healthy overweight [body mass index (in kg/m2): 27.6 ± 0.2] women aged 20–40 y. Results: Energy intake, mean (± SEM) body weight (LGI diet: –1.9 ± 0.5 kg; HGI diet: –1.3 ± 0.3 kg), and fat mass (LGI diet: –1.0 ± 0.4 kg; HGI diet: –0.4 ± 0.3 kg) decreased over time, but the differences between groups were not significant. No significant differences were observed between groups in fasting serum insulin, homeostasis model assessment for relative insulin resistance, homeostasis model assessment for ß cell function, triacylglycerol, nonesterified fatty acids, or HDL cholesterol. However, a 10% decrease in LDL cholesterol (P < 0.05) and a tendency to a larger decrease in total cholesterol (P = 0.06) were observed with consumption of the LGI diet as compared with the HGI diet. Conclusions: This study does not support the contention that low-fat LGI diets are more beneficial than HGI diets with regard to appetite or body-weight regulation as evaluated over 10 wk. However, it confirms previous findings of a beneficial effect of LGI diets on risk factors for ischemic heart disease. Key Words: Obesity • fat mass • energy intake • type 2 diabetes • ischemic heart disease • cholesterol • triacylglycerol • glucose • insulin
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