| 1. |
- 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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| 2. |
- Jenniskens, Peter, et al.
(författare)
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Fall, recovery, and characterization of the Novato L6 chondrite breccia
- 2014
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Ingår i: Meteoritics and Planetary Science. - : Wiley. - 1086-9379. ; 49:8, s. 1388-1425
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Tidskriftsartikel (refereegranskat)abstract
- The Novato L6 chondrite fragmental breccia fell in California on 17 October 2012, and was recovered after the Cameras for Allsky Meteor Surveillance (CAMS) project determined the meteor's trajectory between 95 and 46 km altitude. The final fragmentation from 42 to 22 km altitude was exceptionally well documented by digital photographs. The first sample was recovered before rain hit the area. First results from a consortium study of the meteorite's characterization, cosmogenic and radiogenic nuclides, origin, and conditions of the fall are presented. Some meteorites did not retain fusion crust and show evidence of spallation. Before entry, the meteoroid was 35 +/- 5 cm in diameter (mass 80 +/- 35 kg) with a cosmic-ray exposure age of 9 +/- 1 Ma, if it had a one-stage exposure history. A two-stage exposure history is more likely, with lower shielding in the last few Ma. Thermoluminescence data suggest a collision event within the last similar to 0.1 Ma. Novato probably belonged to the class of shocked L chondrites that have a common shock age of 470 Ma, based on the U, Th-He age of 420 +/- 220 Ma. The measured orbits of Novato, Jesenice, and Innisfree are consistent with a proposed origin of these shocked L chondrites in the Gefion asteroid family, perhaps directly via the 5: 2 mean-motion resonance with Jupiter. Novato experienced a stronger compaction than did other L6 chondrites of shock-stage S4. Despite this, a freshly broken surface shows a wide range of organic compounds.
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| 3. |
- Carneiro de Freitas, Rui, et al.
(författare)
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Prevalence of Visual Impairment in Portugal : study design and initial results
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Information about the prevalence of visual impairment is fundamental to define policies that deal with vision loss. The aim of this study is to determine the prevalence of visual impairment (VI) in the population looking for eye care in public hospitals in Portugal.Methods We designed an observation, cross-sectional prospective study (Prevalence and Costs of Visual Impairment in Portugal: PC-VIP study) to investigate the prevalence of VI in patients attending outpatient appointments in four public hospitals in Portugal. Hospital selected provide from general eye care (3-6 ophthalmologists) to high-specialized eye care (40+ ophthalmologists) that in total have between 120-140K hospital appointments per year. Files of patients are analysed weekly to detect patients with VI. Inclusion criteria were: visual acuity equal or worse than 0.5 (USA definition 20/40) in the better eye and/or a visual field of less than 20deg. Cases are selected by trained hospital staff and inserted in a database. Data collected included demographic information, acuity from both eyes, qualitative information about visual field (good, reduced, requires investigation), main diagnosis, secondary diagnosis and comorbidities. Diagnoses were classified according with ICD9.Results We have now detected 2462 cases of VI that correspond to 4 to 33 weeks of data collection. The number of weeks is variable because collection did not start simultaneously in all sites. From the number of cases detected, 58% were female, 1.9% were under 20y, 8.2% were between 20y and 50y and 89.9% were ≥50y. The mean prevalence of visual impairment was 13.6% (SD=5.6) using the USA definition and it was 7.0%(SD=4.1) using the WHO definition (acuity equal or worse than 0.3 or ~20/63). With a methodology that controls for demographics the lowest and highest estimates were calculated. Considering the USA definition, the prevalence in the general population would be in the range 0.4 -0.4% (age<40y) and 0.8-2.4% (age>=40y). Considering WHO definition, it would be 0.2-0.5% (age<40y) and 0.4-1.0% (age>=40y).Conclusions A hospital-based study can provide effective estimates of the prevalence of visual impairment in a population. Estimates for the country are in agreement with the expected results that can be deducted from neighbour countries and self-reported visual impairment in census 2001.
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| 4. |
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| 5. |
- Macedo, António Filipe, et al.
(författare)
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Investigating unstable fixation in patients with macular disease
- 2011
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 52:3, s. 1275-1280
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Tidskriftsartikel (refereegranskat)abstract
- Purpose.: To assess the effect on visual acuity of compensating fixation instability by controlling retinal image motion in people with macular disease.Methods.: Ten patients with macular disease participated in this study. Crowded and noncrowded visual acuity were measured using an eye tracking system to compensate for fixation instability. Four conditions, corresponding to four levels of retinal image motion, were tested: no compensation (normal motion), partial compensation (reduced motion), total compensation (no motion), and overcompensation (increased motion). Fixation stability and the number of preferred retinal loci were also measured.Results.: Modulating retinal image motion had the same effect on crowded and noncrowded visual acuity (P = 0.601). When fixation instability was overcompensated, acuity worsened by 0.1 logMAR units (P < 0.001) compared with baseline (no compensation) and remained equal to baseline for all other conditions.Conclusions.: In people with macular disease, retinal image motion caused by fixation instability does not reduce either crowded or noncrowded visual acuity. Acuity declines when fixation instability is overcompensated, showing limited tolerance to increased retinal image motion. The results provide evidence that fixation instability does not improve visual acuity and may be a consequence of poor oculomotor control.
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| 6. |
- Marques, Ana Patricia, et al.
(författare)
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Estimating the cost of visual impairment : initial results
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Vision loss can have a substantial human and economic impact on individuals and society that include disability, loss of productivity and reduction in quality of life. The purpose of this study was to estimate economic burden of visual impairment in Portugal.Methods: A prevalence-based cost of illness approach was adopted to estimate costs of vision impairment. We estimated direct medical costs and indirect economic costs. Direct medical hospital costs were determined using a bottom up approach. For those meeting the inclusion criteria (visual acuity of 20/40 or 0.5decimal or worse in the better eye and/or visual field of less than 20deg) we estimated direct costs by collecting information from administrative records that included: physician’s office visits, emergency and outpatient visits. We developed a survey based in parts of the annotated cost questionnaire-HERU Discussion Paper N.03/01 (UK Working Party on Patient Costs) and the Service Receipt Inventory-European Version. Using the questionnaire that we developed, in face-to-face interviews, we collect direct medical expenditures supported by patients that included: costs with medical prescriptions, low vision aids and devices. With the same questionnaire we collected information for indirect costs calculations. Indirect costs were calculated by estimating the value of productivity losses including employment participation, absenteeism and caregiver costs.Results: Results presented here correspond to 442 patients that met the inclusion criteria. The four main causes of visual impairment in this sample were Diabetic Retinopathy, Cataract, Glaucoma and Age-related macular degeneration. Direct medical hospital costs were accountable for 12% of total costs calculated. Patient expenditures represented 25% of expenses with visual impairment and indirect costs corresponded to 63% of the total. From this data we estimated that the average annual direct cost per patient with VI was 958 euro and average annual indirect cost was 1655 euro.Conclusions: With the instruments and methodology that was adopted we were able quantify direct medical hospital costs as well as indirect costs of visual impairment. Results of this study show that more than half of the costs with VI are indirect. This highlights that particular attention should be given to costs that arise for individuals with vision loss.
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| 7. |
- Pesudovs, Konrad, et al.
(författare)
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Measuring the Patient's Perspective.
- 2013
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Ingår i: Optometry and Vision Science. - : Ovid Technologies (Wolters Kluwer Health). - 1538-9235 .- 1040-5488. ; 90:8, s. 717-719
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Ryman-Tubb, Toby, et al.
(författare)
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Comparative pathology of dog and human prostate cancer
- 2022
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Ingår i: Veterinary medicine and science. - : John Wiley & Sons. - 2053-1095. ; 8:1, s. 110-120
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Tidskriftsartikel (refereegranskat)abstract
- Though relatively rare in dogs, prostate cancer (PCa) is the most common non-cutaneous cancer in men. Human and canine prostate glands share many functional, anatomical and physiological features. Due to these similarities, canine PCa has been proposed as a model for PCa in men. PCa is typically androgen-dependent at diagnosis in men and for this reason, androgen deprivation therapies (ADT) are important treatments for advanced PCa in men. In contrast, there is some evidence that PCa is diagnosed more commonly in castrate dogs, at which point, limited therapeutic options are available. In men, a major limitation of current ADT is that progression to a lethal and incurable form of PCa, termed castrate-resistant prostate cancer (CRPC), is common. There is, therefore, an urgent need for a better understanding of the mechanism of PCa initiation and progression to CRPC to enable the development of novel therapeutic approaches. This review focuses on the functional, physiological, endocrine and histopathological similarities and differences in the prostate gland of these species. In particular, we focus on common physiological roles for androgen signalling in the prostate of men and dogs, we review the short- and longer-term effects of castration on PCa incidence and progression in the dog and relate how this knowledge may be relevant to understanding the mechanisms of CRPC in men.
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| 9. |
- Svensson, Maria A., et al.
(författare)
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Testing mutual exclusivity of ETS rearranged prostate cancer
- 2011
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 0023-6837 .- 1530-0307. ; 91:3, s. 404-412
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a clinically heterogeneous and multifocal disease. More than 80% of patients with prostate cancer harbor multiple geographically discrete cancer foci at the time of diagnosis. Emerging data suggest that these foci are molecularly distinct consistent with the hypothesis that they arise as independent clones. One of the strongest arguments is the heterogeneity observed in the status of E26 transformation specific (ETS) rearrangements between discrete tumor foci. The clonal evolution of individual prostate cancer foci based on recent studies demonstrates intertumoral heterogeneity with intratumoral homogeneity. The issue of multifocality and interfocal heterogeneity is important and has not been fully elucidated due to lack of the systematic evaluation of ETS rearrangements in multiple tumor sites. The current study investigates the frequency of multiple gene rearrangements within the same focus and between different cancer foci. Fluorescence in situ hybridization (FISH) assays were designed to detect the four most common recurrent ETS gene rearrangements. In a cohort of 88 men with localized prostate cancer, we found ERG, ETV1, and ETV5 rearrangements in 51% (44/86), 6% (5/85), and 1% (1/86), respectively. None of the cases demonstrated ETV4 rearrangements. Mutual exclusiveness of ETS rearrangements was observed in the majority of cases; however, in six cases, we discovered multiple ETS or 50 fusion partner rearrangements within the same tumor focus. In conclusion, we provide further evidence for prostate cancer tumor heterogeneity with the identification of multiple concurrent gene rearrangements. Laboratory Investigation (2011) 91, 404-412; doi: 10.1038/labinvest.2010.179; published online 25 October 2010
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