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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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| 3. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 4. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 5. |
- Baskaran, Karthikeyan, et al.
(författare)
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Effects of Optical Defocus on Resolution Acuity in Preferred Retinal Locus
- 2011
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Ingår i: <em>Invest Ophthalmol Vis Sci</em> 2011;52: E-Abstract 1900..
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Konferensbidrag (refereegranskat)abstract
- PurposeResolution acuity in the peripheral visual field is primarily limited by retinal sampling. In healthy eyes, the correction of peripheral refractive errors does not produce significant visual benefits other than improved detection and low contrast acuity. However, studies (Lundstrom L et al, Optom Vis Sci, 2007;84:1046-52) have shown that peripheral refractive corrections improve resolution acuity in subjects with central visual field loss (CFL) who have an established preferred retinal locus (PRL). The aim of this study was to evaluate the effect of optical defocus on high contrast resolution acuity in the PRL. MethodsResolution acuity was evaluated under spherical defocus in the PRL of three low vision subjects (mean age 75 years) with long standing CFL (due to age-related macular degeneration). Off-axis refractive error at the PRL was measured by an open-field COAS-HD VR aberrometer and was corrected accordingly. The PRL for subject 1 was located at 10{degrees} in the temporal visual field (left eye), subject 2 at 20{degrees} in the nasal visual field (right eye) and subject 3 at 15{degrees} in the inferior visual field (left eye). Stimuli consisting of high-contrast Gabor patches with a visible diameter of 3{o} were presented on a CRT monitor situated 1.0 meter from the subject. Resolution thresholds for static visual acuity (SVA) and dynamic visual acuity (DVA) were obtained using an adaptive Bayesian algorithm. Fixation was aided using illuminated concentric rings covering {+/-}25{degrees} in the visual field. Defocus was altered in 1D steps up to {+/-}4D. When measuring DVA, the sine-wave gratings drifted within the Gaussian envelope at an angular velocity of 1{degrees}/sec. ResultsResolution thresholds for both SVA and DVA in the PRL varied significantly with the amount of optical defocus. The results show a 2 - 3 line decrease (logMAR) in SVA and DVA with 4 D positive and negative defocus. There was no significant difference between SVA and DVA with increasing defocus. In the absence of defocus, SVA was significantly better than DVA in the PRL. ConclusionsDefocus as low as one dioptre has an impact on both static and dynamic high contrast resolution acuity for CFL subjects using a PRL. The results of this study suggest that, for CFL subjects using a PRL, resolution acuity is not only sampling limited but also influenced by the optics of the eye.
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| 6. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 7. |
- Kristiansson, Håkan, et al.
(författare)
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Effect of Optical Defocus on Peripheral Resolution Acuity in Old Healthy Emmetropes
- 2011
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Konferensbidrag (refereegranskat)abstract
- Background: A recent study by Rosén et al found peripheral low contrast resolution acuity, but not high contrast acuity, to be affected by defocus in young healthy eyes. Since aging causes considerable degradation in peripheral optics even in healthy subjects we wanted to see if, older subjects were also sensitive to defocus in low contrast acuity. Purpose: The aim of this study was to evaluate the effect of optical defocus on high and low contrast resolution acuity in the peripheral visual field of healthy older emmetropes. Subjects: High- and low-contrast resolution acuity was evaluated under spherical defocus in the 20° nasal visual field of four healthy older emmetropic subjects. The off-axis refractive error at the 20° nasal visual field was measured by a COAS-HD VR aberrometer and was corrected accordingly for each subject. Methods: Resolution thresholds for visual acuity (VA) were obtained using stimuli consisting of high- (100%) and low- (10%) contrast gratings that were presented on a CRT monitor situated 1.0 meter from the subject. Stimuli, 3° in diameter were presented for 300 ms using a 2AFC paradigm. Two repeated measurements, for both high and low contrast, were obtained for each point of defocus in 1.0 D steps up to ±4 D at 45mm vertex distance. The results are corrected to effective defocus at the corneal plane. Results: Defocus had no visible effect on high contrast VA, although there was a slight decrease in VA with higher amounts of positive defocus. However, defocus was found to have a significant effect on low contrast VA. Moreover, low contrast resolution was more sensitive to positive defocus than the negative defocus. Conclusions: Defocus has an impact on low contrast resolution whereas no such effect was found for high contrast resolution. These results are similar to those obtained by Rosén et al1 in young eyes. These results suggest that low contrast optotypes could possibly be used for determining subjective refraction in low vision subjects.
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| 8. |
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| 9. |
- Lewis, Peter, 1971-, et al.
(författare)
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Dynamic Visual Acuity in the Peripheral Visual Field Using Gabor Patches
- 2010
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Konferensbidrag (refereegranskat)abstract
- Purpose:To evaluate dynamic visual acuity (DVA) in the peripheral visual field. This ability is important within the areas of sports, traffic safety, as well as for people with low vision; specifically those with central visual field loss. In this study we investigated both static- and dynamic visual acuity in the periphery of normally sighted observers using Gabor patches. Methods:DVA and static visual acuity (SVA) was measured on the right eye of normally sighted emmetropes. Stimuli consisted of high-contrast Gabor patches; sine wave gratings multiplied by a Gaussian hull with a diameter of 2º, with the sine gratings drifting at 1, 2, and 4 degrees per second. Stimuli were presented, using MATLAB and Psychophysics Toolbox, on one of seven CRT monitors at the following retinal eccentricities: 10, 20 and 30 degrees, nasally and temporally as well as in the fovea. Subjects were informed to maintain fixation on a central fixation object during measurements at eccentric locations. An Adaptive Bayesian algorithm was employed to determine resolution thresholds at each eccentricity. Results:The results show a trend towards both better static- and dynamic visual acuities for the temporal visual field at retinal eccentricities 20° and 30° compared to nasally. There appears to be a more rapid decrease in both static- and dynamic visual acuity with increasing eccentricity for the nasal visual field. In addition, we did not find any difference in DVA and SVA in the peripheral visual field for the velocities used in this study. Conclusions:Results of these first preliminary measurements suggest that dynamic visual acuity measured with drifting Gabor patches is greater in the temporal visual field for eccentricities 20 degrees or larger. To confirm these results more measurements need to be performed on a lager sample of subjects.
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| 10. |
- Lewis, Peter, 1971-, et al.
(författare)
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Naso-temporal Asymmetry of Peripheral Static and Dynamic Visual Acuity
- 2011
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Konferensbidrag (refereegranskat)abstract
- SummaryStatic and dynamic visual acuity was evaluated in the peripheral visual field on normally sighted emmetropes. The results show a significant asymmetry for both static and dynamic visual acuity between the nasal and temporal visual fields. IntroductionIt is well known that visual performance thresholds decrease rapidly with increasing retinal eccentricity1. This reduction in performance can be attributed to both optical factors and reduced neural sampling2-3; the latter being the predominant limiting factor in the peripheral retina3. Previous studies have shown that slowly moving stimuli are more easily resolved than stationary stimuli in the peripheral retina4. There is little evidence published regarding resolution thresholds for moving stimuli in more than a few limited directions in the visual field. In this study, static visual acuity (SVA) and dynamic visual acuity (DVA) thresholds were measured at 10° intervals both nasally and temporally on healthy, young emmetropes. DVA was measured at angular velocities of 1 °/s and 2 °/s using drifting Gabor patches. DiscussionStatic and dynamic visual acuity was measured on the right eye of emmetropic subjects. Results for SVA showed significantly better resolution in the temporal visual field compared with the nasal visual field at eccentricities 20° and beyond. The mean difference in acuity at 20° was approximately 0.2 LogMAR and at 30°, 0.3 LogMAR. The difference between the thresholds for DVA showed a similar naso-temporal asymmetry; the reduction in DVA paralleling the decrease in SVA for eccentricities 10° and beyond. No significant differences were observed between averaged results of SVA and DVA for the eccentricities tested in this study. ConclusionsThe results of this study confirm previous research conducted by Frisén (1987) showing better resolution for static stimuli presented in the temporal visual field compared to the nasal visual field. We have found that this is also true for DVA.
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