532 research outputs found
Psychological, behavioral and social effects of disclosing Alzheimer's disease biomarkers to research participants: a systematic review.
BACKGROUND: Current Alzheimer's disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants. METHODS: We performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group. RESULTS: Fourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning. CONCLUSION: In cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed. TRIAL REGISTRATION: PROSPERO international prospective register for systematic reviews CRD42016035388 . Registered 19 February 2016
Drivers of Bornean orangutan distribution across a multiple-use tropical landscape
Logging and conversion of tropical forests in Southeast Asia have resulted in the expansion of landscapes containing a mosaic of habitats that may vary in their ability to sustain local biodiversity. However, the complexity of these landscapes makes it difficult to assess abundance and distribution of some species using ground-based surveys alone. Here we deployed a combination of ground-transects and aerial surveys to determine drivers of the Critically Endangered Bornean Orangutan (Pongo pygmaeus) distribution across a large multiple-use landscape in Sabah, Malaysian Borneo. Ground-transects and aerial surveys using drones were conducted for orangutan nests and strangler fig trees (an important food resource) in 48 survey areas across 76 km2, within a study landscape of 261 km2 Orangutan nest count data were fitted to models accounting for variation in land use, above-ground carbon density (ACD; a surrogate for forest quality), strangler fig density, and elevation (between 117 and 675 m). Orangutan nest counts were significantly higher in all land uses possessing natural forest cover, regardless of degradation status, than in monoculture plantations. Within these natural forests, nest counts increased with higher ACD and strangler fig density, but not with elevation. In logged forest (ACD 14 – 150 Mg ha-1), strangler fig density had a significant, positive relationship with orangutan nest counts, but this relationship disappeared in forest with higher carbon content (ACD 150- 209 Mg ha-1). Based on an area-to-area comparison, orangutan nest counts from ground transects were higher than from counts derived from aerial surveys, but this did not constitute a statistically significant difference. Although the difference in nest counts was not significantly different, this analysis indicates that both methods under-sample the total number of nests present within a given area. Aerial surveys are therefore a useful method for assessing orangutan habitat use over large areas, however the under-estimation of nest counts by both methods suggests that a small number of ground surveys should be retained in future surveys using this technique, particularly in areas with dense understory vegetation. This study shows that even highly degraded forests may be suitable orangutan habitat as long as strangler fig trees remain intact after areas of forest are logged. Enrichment planting of strangler figs may therefore be a valuable tool for orangutan conservation in these landscapes
The fundamental pro-groupoid of an affine 2-scheme
A natural question in the theory of Tannakian categories is: What if you
don't remember \Forget? Working over an arbitrary commutative ring , we
prove that an answer to this question is given by the functor represented by
the \'etale fundamental groupoid \pi_1(\spec(R)), i.e.\ the separable
absolute Galois group of when it is a field. This gives a new definition
for \'etale \pi_1(\spec(R)) in terms of the category of -modules rather
than the category of \'etale covers. More generally, we introduce a new notion
of "commutative 2-ring" that includes both Grothendieck topoi and symmetric
monoidal categories of modules, and define a notion of for the
corresponding "affine 2-schemes." These results help to simplify and clarify
some of the peculiarities of the \'etale fundamental group. For example,
\'etale fundamental groups are not "true" groups but only profinite groups, and
one cannot hope to recover more: the "Tannakian" functor represented by the
\'etale fundamental group of a scheme preserves finite products but not all
products.Comment: 46 pages + bibliography. Diagrams drawn in Tik
Association of tamoxifen use and reduced risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers
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Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin
Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al
Increased Diacylglycerols Characterize Hepatic Lipid Changes in Progression of Human Nonalcoholic Fatty Liver Disease; Comparison to a Murine Model
The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to cirrhosis. While differences in liver lipids between disease states have been reported, precise composition of phospholipids and diacylglycerols (DAG) at a lipid species level has not been previously described. The goal of this study was to characterize changes in lipid species through progression of human NAFLD using advanced lipidomic technology and compare this with a murine model of early and advanced NAFLD.Utilizing mass spectrometry lipidomics, over 250 phospholipid and diacylglycerol species (DAGs) were identified in normal and diseased human and murine liver extracts.Significant differences between phospholipid composition of normal and diseased livers were demonstrated, notably among DAG species, consistent with previous reports that DAG transferases are involved in the progression of NAFLD and liver fibrosis. In addition, a novel phospholipid species (ether linked phosphatidylinositol) was identified in human cirrhotic liver extracts.Using parallel lipidomics analysis of murine and human liver tissues it was determined that mice maintained on a high-fat diet provide a reproducible model of NAFLD in regards to specificity of lipid species in the liver. These studies demonstrated that novel lipid species may serve as markers of advanced liver disease and importantly, marked increases in DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels characteristic of the disease and specific DAG species might be important lipid signaling molecules in the progression of NAFLD
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Evaluation of a complex healthcare intervention to increase smoking cessation in pregnant women: interrupted time series analysis with economic evaluation
OBJECTIVES: To evaluate the effectiveness of a complex intervention to improve referral and treatment of pregnant smokers in routine practice, and to assess the incremental costs to the National Health Service (NHS) per additional woman quitting smoking. DESIGN: Interrupted time series analysis of routine data before and after introducing the intervention, within-study economic evaluation. SETTING: Eight acute NHS hospital trusts and 12 local authority areas in North East England. PARTICIPANTS: 37 726 records of singleton delivery including 10 594 to mothers classified as smoking during pregnancy. INTERVENTIONS: A package of measures implemented in trusts and smoking cessation services, aimed at increasing the proportion of pregnant smokers quitting during pregnancy, comprising skills training for healthcare and smoking cessation staff; universal carbon monoxide monitoring with routine opt-out referral for smoking cessation support; provision of carbon monoxide monitors and supporting materials; and an explicit referral pathway and follow-up protocol. MAIN OUTCOME MEASURES: Referrals to smoking cessation services; probability of quitting smoking during pregnancy; additional costs to health services; incremental cost per additional woman quitting. RESULTS: After introduction of the intervention, the referral rate increased more than twofold (incidence rate ratio=2.47, 95% CI 2.16 to 2.81) and the probability of quitting by delivery increased (adjusted OR=1.81, 95% CI 1.54 to 2.12). The additional cost per delivery was £31 and the incremental cost per additional quit was £952; 31 pregnant women needed to be treated for each additional quitter. CONCLUSIONS: The implementation of a system-wide complex healthcare intervention was associated with significant increase in rates of quitting by delivery.This article presents independent research funded by the NIHR School for Public Health Research (SPHR). NIHR SPHR is a partnership between the Universities of Sheffield, Bristol, Cambridge, Exeter, University College London; The London School for Hygiene and Tropical Medicine; the LiLaC collaboration between the Universities of Liverpool and Lancaster; and Fuse, the Centre for Translational Research in Public Health, a collaboration between Newcastle, Durham, Northumbria, Sunderland and Teesside Universities. Fuse is a UK Clinical Research Collaboration (UKCRC) Public Health Research Centres of Excellence, which receives funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, and the National Institute for Health Research
IPSS-independent prognostic value of plasma CXCL10, IL-7 and IL-6 levels in myelodysplastic syndromes
Recent studies suggest a powerful prognostic value for plasma cytokine levels in primary myelofibrosis (interleukin (IL)-2R, IL-8, IL-12, IL-15 and C–X–C motif chemokine 10 (CXCL10)) and large-cell lymphoma (IL-2R, IL-8, IL-10, IL-12, CXCL9 and CXCL10). To examine the possibility of a similar phenomenon in myelodysplastic syndromes (MDS), we used multiplex enzyme-linked immunosorbent assay to measure 30 plasma cytokines in 78 patients with primary MDS. Compared with normal controls (n=35), the levels of 19 cytokines were significantly altered. Multivariable analysis identified increased levels of CXCL10 (P<0.01), IL-7 (P=0.02) and IL-6 (P=0.07) as predictors of shortened survival; the survival association remained significant when the Cox model was adjusted for the International Prognostic Scoring System, age, transfusion-need or thrombocytopenia. MDS patients with normal plasma levels of CXCL10, IL-7 and IL-6 lived significantly longer (median survival 76 months) than those with elevated levels of at least one of the three cytokines (median survival 25 months) (P<0.01). Increased levels of IL-6 were associated with inferior leukemia-free survival, independent of other prognostic factors (P=0.01). Comparison of plasma cytokines between MDS (n=78) and primary myelofibrosis (n=127) revealed a significantly different pattern of abnormalities. These observations reinforce the concept of distinct and prognostically relevant plasma cytokine signatures in hematological malignancies
Relaxation of Adaptive Evolution during the HIV-1 Infection Owing to Reduction of CD4+ T Cell Counts
Background: the first stages of HIV-1 infection are essential to establish the diversity of virus population within host. It has been suggested that adaptation to host cells and antibody evasion are the leading forces driving HIV evolution at the initial stages of AIDS infection. in order to gain more insights on adaptive HIV-1 evolution, the genetic diversity was evaluated during the infection time in individuals contaminated by the same viral source in an epidemic cluster. Multiple sequences of V3 loop region of the HIV-1 were serially sampled from four individuals: comprising a single blood donor, two blood recipients, and another sexually infected by one of the blood recipients. the diversity of the viral population within each host was analyzed independently in distinct time points during HIV-1 infection.Results: Phylogenetic analysis identified multiple HIV-1 variants transmitted through blood transfusion but the establishing of new infections was initiated by a limited number of viruses. Positive selection (d(N)/d(S)>1) was detected in the viruses within each host in all time points. in the intra-host viruses of the blood donor and of one blood recipient, X4 variants appeared respectively in 1993 and 1989. in both patients X4 variants never reached high frequencies during infection time. the recipient, who X4 variants appeared, developed AIDS but kept narrow and constant immune response against HIV-1 during the infection time.Conclusion: Slowing rates of adaptive evolution and increasing diversity in HIV-1 are consequences of the CD4+ T cells depletion. the dynamic of R5 to X4 shift is not associated with the initial amplitude of humoral immune response or intensity of positive selection.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fed Univ Para, Inst Biotechnol, BR-66059 Belem, Para, BrazilUniv São Paulo, Inst Trop Med, São Paulo, SP, BrazilCDC, Ctr Dis Control & Prevent, Branch Lab, Atlanta, GA 30333 USAUniv Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USABlood Syst Res Inst, San Francisco, CA USABlood Syst Inc, San Francisco, CA USAUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilFAPESP: 07/52841-8Web of Scienc
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