Various magnetic resonance (MR) techniques are used to study the pathological evolution of demyelinating diseases, such as multiple sclerosis (MS). However, few studies have validated MR derived ...measurements with histopathology. Here, we determine the correlation of myelin water imaging, an MR measure of myelin content, with quantitative histopathologic measures of myelin density. The multi-component T2 distribution of water was determined from 25 formalin-fixed MS brain samples using a multi-echo T2 relaxation MR experiment. The myelin water fraction (MWF), defined as T2 signal below 30 milliseconds divided by the total signal, was determined for various regions of interest and compared to Luxol fast blue (myelin stain) mean optical density (OD) for each sample. MWF had a strong correlation with myelin stain mean (range) R2-/0.67 (0.45+ 0.92), validating MWF as a measure of myelin density. This quantitative technique has many practical applications for the in vivo monitoring of demyelination and remyelination in a variety of disorders of myelin.
Experimental island invasion of house mice Nathan, Helen W; Clout, Mick N; MacKay, Jamie W. B ...
Population ecology,
April 2015, Letnik:
57, Številka:
2
Journal Article
Recenzirano
The ability of invasive species to recurrently establish populations from small numbers of founders, while threatened species struggle at the same low population sizes, is a paradox in conservation ...biology. Little is known about the mechanisms contributing to the post-arrival success of low density invasive populations as most invasive species research focuses on established, high density populations. Experimental studies are powerful, but generally limited to laboratory or invertebrate experiments. Here, we experimentally demonstrate that vertebrate mammal invasion from a very small (n = 2) number of founders follows relatively simple deterministic predictions. An intentional island invasion of introduced house mice (Mus musculus Linnaeus) from one founding pair closely tracked the density dependent logistic growth curve and reached the seasonal carrying capacity of a previously extant population in only 5 months. Carrying capacity reflected both density dependent and independent processes. In contrast to the previously incumbent population, the invading population retained a marked genetic signal of its recent founder event, but the populations were otherwise demographically indistinguishable. Stochastic events such as individual variability, supplemental immigration and ecological release, but not Allee effects, played important roles during colonisation, but following establishment dynamics rapidly became deterministic, with little demographic impact of reduced genetic diversity. The small population paradigm appears to have little influence on the population dynamics of highly successful invasive species.
Synovitis is hypothesized to play a role in the development and growth of osteophytes. Our objectives were to use hybrid positron emission tomography-magnetic resonance imaging (PET-MRI) to (1) ...determine whether synovitis adjacent to peripheral bone subregions with increased metabolic activity is greater than adjacent to regions without increased metabolic activity and (2) assess the association between subregional bone metabolic activity and adjacent synovitis.
We recruited 11 participants (22 knees) with a diagnosis of OA in at least one knee. Simultaneous bilateral knee PET-MRI was performed. We quantified bone metabolic activity using the radiotracer 18Fsodium fluoride (18FNaF) with calculation of maximum standardized uptake values (SUVmax). Synovitis was quantified using dynamic contrast-enhanced MRI with calculation of Ktrans. Bone subregions were coded as osteophyte (OP), focal increased 18FNaF uptake without osteophyte (FIU), or normal (no osteophyte or FIU). We used robust linear mixed effects models to assess differences in adjacent Ktrans between different subregion types and to assess association between Ktrans and adjacent SUVmax.
94 OPs were detected (59 MOAKS grade 1, 30 grade 2, 5 grade 3), along with 28 FIU and 18 normal subregions. Ktrans was higher adjacent to FIU (adjusted mean 95% CI = 0.06 0.03,0.09) and OPs (0.08 0.05,0.11) when compared to normal bone subregions (0.03 0.00,0.09). PET SUVmax was positively associated with adjacent Ktrans (β95% CI = 0.018 0.008,0.027).
Synovitis is more intense adjacent to peripheral bone regions with increased metabolic activity than those without, although there is some overlap. Subregional bone metabolic activity is positively associated with intensity of adjacent synovitis.
Exosomes are released from multiple cell types, contain protein and RNA species, and have been exploited as a novel reservoir for disease biomarker discovery. They can transfer information between ...cells and may cause pathology, for example, a role for exosomes has been proposed in the pathophysiology of Alzheimer's disease. Although studied in several biofluids, exosomes have not been extensively studied in the cerebrospinal fluid (CSF) from humans. The objective of this study was to determine: 1) whether human CSF contains exosomes and 2) the variability in exosomal protein content across individuals.
CSF was collected from 5 study participants undergoing thoraco-abdominal aortic aneurysm repair (around 200 - 500 ml per participant) and low-density membrane vesicles were concentrated by ultracentrifugation. The presence of exosomes was determined by western blot for marker proteins, isopycnic centrifugation on a sucrose step gradient and transmission electron microscopy with immuno-labelling. Whole protein profiling was performed using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR).
Flotillin 1 and tumor susceptibility gene 101 (TSG101), two exosomal marker proteins, were identified in the ultracentrifugation pellet using western blot. These markers localized to a density consistent with exosomes following isopycnic centrifugation. Transmission electron microscopy visualized structures consistent with exosomes in size and appearance that labelled positive for flotillin 1. Therefore, the pellet that resulted from ultracentrifugation of human CSF contained exosomes. FT-ICR profiling of this pellet was performed and 84-161 ions were detected per study participant. Around one third of these ions were only present in a single study participant and one third were detected in all five. With regard to ion quantity, the median coefficient of variation was 81% for ions detected in two or more samples.
Exosomes were identified in human CSF and their proteome is a potential new reservoir for biomarker discovery in neurological disorders such as Alzheimer's disease. However, techniques used to concentrate exosomes from CSF need refinement to reduce variability. In this study we used relatively large starting volumes of human CSF, future studies will focus on exosome isolation from smaller 'real life' clinical samples; a key challenge in the development of exosomes as translational tools.
Tipping points – where systems shift radically and potentially irreversibly into a different state – have received considerable attention in ecology. Although there is convincing evidence that human ...drivers can cause regime shifts at local and regional scales, the increasingly invoked concept of planetary scale tipping points in the terrestrial biosphere remains unconfirmed. By evaluating potential mechanisms and drivers, we conclude that spatial heterogeneity in drivers and responses, and lack of strong continental interconnectivity, probably induce relatively smooth changes at the global scale, without an expectation of marked tipping patterns. This implies that identifying critical points along global continua of drivers might be unfeasible and that characterizing global biotic change with single aggregates is inapt.
Over the past decade, evidence has accumulated to suggest that bisexual people experience higher rates of poor mental health outcomes compared to both heterosexual and gay/lesbian individuals. ...However, no previous meta-analyses have been conducted to establish the magnitude of these disparities. To address this research gap, we conducted a systematic review and meta-analysis of studies that reported bisexual-specific data on standardized measures of depression or anxiety. Of the 1,074 full-text articles reviewed, 1,023 were ineligible, predominantly because they did not report separate data for bisexual people (n = 562 studies). Ultimately, 52 eligible studies could be pooled in the analysis. Results indicate that across both outcomes, there is a consistent pattern of lowest rates of depression and anxiety among heterosexual people, while bisexual people exhibit higher or equivalent rates in comparison to lesbian/gay people. On the basis of empirical and theoretical literature, we propose three interrelated contributors to these disparities: experiences of sexual orientation-based discrimination, bisexual invisibility/erasure, and lack of bisexual-affirmative support. Implications for interventions to improve the health and well-being of bisexual people are proposed.
Patients with the sleep apnea/hypopnea syndrome (SAHS) treated by nasal continuous positive airway pressure (CPAP) need to use CPAP long-term to prevent recurrence of symptoms. It is thus important ...to clarify the level of long-term CPAP use and the factors influencing long-term use. We examined determinants of objective CPAP use in 1, 211 consecutive patients with SAHS who were prescribed a CPAP trial between 1986 and 1997. Prospective CPAP use data were available in 1, 155 (95.4%), with a median follow-up of 22 mo (interquartile range IQR, 12 to 36 mo). Fifty-two (4.5%) patients refused CPAP treatment (these were more often female and current smokers); 1,103 patients took CPAP home, and during follow-up 20% stopped treatment, primarily because of a lack of benefit. Methods of survival analysis showed that 68% of patients continued treatment at 5 yr. Independent predictors of long-term CPAP use were snoring history, apnea/hypopnea index (AHI), and Epworth score; 86% of patients with Epworth > 10 and an AHI >/= 30 were still using CPAP at 3 yr. Average nightly CPAP use within the first 3 mo was strongly predictive of long-term use. We conclude that long-term CPAP use is related to disease severity and subjective sleepiness and can be predicted within 3 mo.
Arterial blood pressure rises at apnea termination, and there is increasing evidence that the sleep apnea-hypopnea syndrome (SAHS) is associated with daytime hypertension but no randomized controlled ...trial evidence of whether SAHS treatment reduces blood pressure exists. We, therefore, conducted a randomized placebo-controlled cross-over study of the effects of 4 wk of continuous positive airway pressure (CPAP) or oral placebo on 24-h blood pressure in 68 patients (55 males, 13 females; median apnea-hypopnea index AHI, 35) not receiving hypotensive medication. Ambulatory blood pressure was recorded for the last 48 h of each treatment. Epworth Sleepiness Score (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ) were also recorded. All patients were normotensive. There was a small decrease in 24-h diastolic blood pressure (placebo, 79.2 SE 0.9 mm Hg; CPAP, 77.8 SE 1.0 mm Hg; p = 0.04) with the greatest fall occurring between 2:00 A.M. and 9:59 A.M. The observed decrease in 24-h diastolic blood pressure was greater in two a priori groups, CPAP use > or = 3.5 h per night (81.5 SE 1.2 mm Hg; 79.6 SE 1.2 mm Hg; p = 0.03) and those with more than twenty 4% desaturations per hour (82.4 SE 2.1 mm Hg; 77.4 SE 2.1 mm Hg; p = 0.002). Systolic pressure also fell in the latter group (133.1 SE 2.8 mm Hg; 129.1 SE 2.1 mm Hg; p = 0.009). Desaturation frequency was the best predictor of diastolic blood pressure fall with CPAP (r = 0.38; p = 0.002). Both ESS and FOSQ domains improved. Thus, CPAP can reduce blood pressure in patients with SAHS, particularly in those with nocturnal oxygen desaturation, but the decrease is small.
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