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991.
Marie Abitbol Christophe Hitte Philippe Bossé Nicolas Blanchard-Gutton Anne Thomas Lionel Martignat Stéphane Blot Laurent Tiret 《PloS one》2015,10(9)
An autosomal recessive neuromuscular disorder characterized by skeletal muscle weakness, fatigability and variable electromyographic or muscular histopathological features has been described in the two related Sphynx and Devon Rex cat breeds (Felis catus). Collection of data from two affected Sphynx cats and their relatives pointed out a single disease candidate region on feline chromosome C2, identified following a genome-wide SNP-based homozygosity mapping strategy. In that region, we further identified COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase) as a good candidate gene, since COLQ mutations were identified in affected humans and dogs with endplate acetylcholinesterase deficiency leading to a synaptic form of congenital myasthenic syndrome (CMS). A homozygous c.1190G>A missense variant located in exon 15 of COLQ, leading to a C397Y substitution, was identified in the two affected cats. C397 is a highly-conserved residue from the C-terminal domain of the protein; its mutation was previously shown to produce CMS in humans, and here we confirmed in an affected Sphynx cat that it induces a loss of acetylcholinesterase clustering at the neuromuscular junction. Segregation of the c.1190G>A variant was 100% consistent with the autosomal recessive mode of inheritance of the disorder in our cat pedigree; in addition, an affected, unrelated Devon Rex cat recruited thereafter was also homozygous for the variant. Genotyping of a panel of 333 cats from 14 breeds failed to identify a single carrier in non-Sphynx and non-Devon Rex cats. Finally, the percentage of healthy carriers in a European subpanel of 81 genotyped Sphynx cats was estimated to be low (3.7%) and 14 control Devon Rex cats were genotyped as wild-type individuals. Altogether, these results strongly support that the neuromuscular disorder reported in Sphynx and Devon Rex breeds is a CMS caused by a unique c.1190G>A missense mutation, presumably transmitted through a founder effect, which strictly and slightly disseminated in these two breeds. The presently available DNA test will help owners avoid matings at risk. 相似文献
992.
Background
We sought to examine whether neighborhood deprivation is associated with participation in a large population-based health check. Such analyses will help answer the question whether health checks, which are designed to meet the needs of residents in deprived neighborhoods, may increase participation and prove to be more effective in preventing disease. In Europe, no study has previously looked at the association between neighborhood deprivation and participation in a population-based health check.Methods
The study population comprised 12,768 persons invited for a health check including screening for ischemic heart disease and lifestyle counseling. The study population was randomly drawn from a population of 179,097 persons living in 73 neighborhoods in Denmark. Data on neighborhood deprivation (percentage with basic education, with low income and not in work) and individual socioeconomic position were retrieved from national administrative registers. Multilevel regression analyses with log links and binary distributions were conducted to obtain relative risks, intraclass correlation coefficients and proportional change in variance.Results
Large differences between neighborhoods existed in both deprivation levels and neighborhood health check participation rate (mean 53%; range 35-84%). In multilevel analyses adjusted for age and sex, higher levels of all three indicators of neighborhood deprivation and a deprivation score were associated with lower participation in a dose-response fashion. Persons living in the most deprived neighborhoods had up to 37% decreased probability of participating compared to those living in the least deprived neighborhoods. Inclusion of individual socioeconomic position in the model attenuated the neighborhood deprivation coefficients, but all except for income deprivation remained statistically significant.Conclusion
Neighborhood deprivation was associated with participation in a population-based health check in a dose-response manner, in which increasing neighborhood deprivation was associated with decreasing participation. This suggests the need to develop preventive health checks tailored to deprived neighborhoods. 相似文献993.
Véronique Pantaléon Anna Philibertine Soavelomandroso Sylvie Bouttier Romain Briandet Bryan Roxas Michele Chu Anne Collignon Claire Janoir Gayatri Vedantam Thomas Candela 《PloS one》2015,10(4)
Clostridium difficile is responsible for 15-20% of antibiotic-associated diarrheas, and nearly all cases of pseudomembranous colitis. Among the cell wall proteins involved in the colonization process, Cwp84 is a protease that cleaves the S-layer protein SlpA into two subunits. A cwp84 mutant was previously shown to be affected for in vitro growth but not in its virulence in a hamster model. In this study, the cwp84 mutant elaborated biofilms with increased biomass compared with the parental strain, allowing the mutant to grow more robustly in the biofilm state. Proteomic analyses of the 630Δerm bacteria growing within the biofilm revealed the distribution of abundant proteins either in cell surface, matrix or supernatant fractions. Of note, the toxin TcdA was found in the biofilm matrix. Although the overall proteome differences between the cwp84 mutant and the parental strains were modest, there was still a significant impact on bacterial surface properties such as altered hydrophobicity. In vitro and in vivo competition assays revealed that the mutant was significantly impaired for growth only in the planktonic state, but not in biofilms or in vivo. Taken together, our results suggest that the phenotypes in the cwp84 mutant come from either the accumulation of uncleaved SlpA, or the ability of Cwp84 to cleave as yet undetermined proteins. 相似文献
994.
Forest floor mineral soil mix (FMM) and peat mineral soil mix (PMM) are cover soils commonly used for upland reclamation post open-pit oil sands mining in northern Alberta, Canada. Coarse woody debris (CWD) can be used to regulate soil temperature and water content, to increase organic matter content, and to create microsites for the establishment of microorganisms and vegetation in upland reclamation. We studied the effects of CWD on soil microbial community level physiological profile (CLPP) and soil enzyme activities in FMM and PMM in a reclaimed landscape in the oil sands. This experiment was conducted with a 2 (FMM vs PMM) × 2 (near CWD vs away from CWD) factorial design with 6 replications. The study plots were established with Populus tremuloides (trembling aspen) CWD placed on each plot between November 2007 and February 2008. Soil samples were collected within 5 cm from CWD and more than 100 cm away from CWD in July, August and September 2013 and 2014. Microbial biomass was greater (p<0.05) in FMM than in PMM, in July, and August 2013 and July 2014, and greater (p<0.05) near CWD than away from CWD in FMM in July and August samplings. Soil microbial CLPP differed between FMM and PMM (p<0.01) according to a principal component analysis and CWD changed microbial CLPP in FMM (p<0.05) but not in PMM. Coarse woody debris increased microbial community functional diversity (average well color development in Biolog Ecoplates) in both cover soils (p<0.05) in August and September 2014. Carbon degrading soil enzyme activities were greater in FMM than in PMM (p<0.05) regardless of distance from CWD but were not affected by CWD. Greater microbial biomass and enzyme activities in FMM than in PMM will increase organic matter decomposition and nutrient cycling, improving plant growth. Enhanced microbial community functional diversity by CWD application in upland reclamation has implications for accelerating upland reclamation after oil sands mining. 相似文献
995.
Tess V. Clendenen Justin Rendleman Wenzhen Ge Karen L. Koenig Isaac Wirgin Diane Currie Roy E. Shore Tomas Kirchhoff Anne Zeleniuch-Jacquotte 《PloS one》2015,10(8)
Background
Large epidemiologic studies have the potential to make valuable contributions to the assessment of gene-environment interactions because they prospectively collected detailed exposure data. Some of these studies, however, have only serum or plasma samples as a low quantity source of DNA.Methods
We examined whether DNA isolated from serum can be used to reliably and accurately genotype single nucleotide polymorphisms (SNPs) using Sequenom multiplex SNP genotyping technology. We genotyped 81 SNPs using samples from 158 participants in the NYU Women’s Health Study. Each participant had DNA from serum and at least one paired DNA sample isolated from a high quality source of DNA, i.e. clots and/or cell precipitates, for comparison.Results
We observed that 60 of the 81 SNPs (74%) had high call frequencies (≥95%) using DNA from serum, only slightly lower than the 85% of SNPs with high call frequencies in DNA from clots or cell precipitates. Of the 57 SNPs with high call frequencies for serum, clot, and cell precipitate DNA, 54 (95%) had highly concordant (>98%) genotype calls across all three sample types. High purity was not a critical factor to successful genotyping.Conclusions
Our results suggest that this multiplex SNP genotyping method can be used reliably on DNA from serum in large-scale epidemiologic studies. 相似文献996.
Emily Dansereau Emmanuela Gakidou Marie Ng Jane Achan Roy Burstein Brendan DeCenso Anne Gasasira Gloria Ikilezi Caroline Kisia Samuel H. Masters Pamela Njuguna Thomas A. Odeny Emelda A. Okiro D. Allen Roberts Herbert C. Duber 《PloS one》2015,10(8)
Introduction
Patients receiving antiretroviral therapy (ART) require routine monitoring to track response to treatment and assess for treatment failure. This study aims to identify gaps in monitoring practices in Kenya and Uganda.Methods
We conducted a systematic retrospective chart review of adults who initiated ART between 2007 and 2012. We assessed the availability of baseline measurements (CD4 count, weight, and WHO stage) and ongoing CD4 and weight monitoring according to national guidelines in place at the time. Mixed-effects logistic regression models were used to analyze facility and patient factors associated with meeting monitoring guidelines.Results
From 2007 to 2012, at least 88% of patients per year in Uganda had a recorded weight at initiation, while in Kenya there was a notable increase from 69% to 90%. Patients with a documented baseline CD4 count increased from 69% to about 80% in both countries. In 2012, 83% and 86% of established patients received the recommended quarterly weight monitoring in Kenya and Uganda, respectively, while semiannual CD4 monitoring was less common (49% in Kenya and 38% in Uganda). Initiating at a more advanced WHO stage was associated with a lower odds of baseline CD4 testing. On-site CD4 analysis capacity was associated with increased odds of CD4 testing at baseline and in the future.Discussion
Substantial gaps were noted in ongoing CD4 monitoring of patients on ART. Although guidelines have since changed, limited laboratory capacity is likely to remain a significant issue in monitoring patients on ART, with important implications for ensuring quality care. 相似文献997.
Background
In the caregiving literature there is a common assertion that a higher level of carer stress is a critical determinant of premature ending of homecare. However, this contention has not been systematically assessed. We therefore systematically reviewed and meta-analysed the prospective association between various forms of carer stress and subsequent institutionalisation of community-dwelling older people.Methods
Systematic literature search of prospective studies measuring carer stress at baseline and institutionalisation at follow-up. Given substantial interchangeability in the measurement of carer stress, we included a wide number of exposure measures, namely: carer stress, burden, depression, distress, anxiety, burnout, and strain. Institutionalisation included both acute and long-term care utilisation. The standardised mean difference between stressed and non-stressed carers was the primary measure of effect. We assessed study quality with the Crowe Critical Appraisal Tool (CCAT). Pre-planned sensitivity analysis included examination of estimates according to study size; decade published; study quality according to quartiles of CCAT scores; population; follow-up period; study design and impact of adjusted or unadjusted estimates.Results
The search yielded 6,963 articles. After exclusions, we analysed data from 54 datasets. The meta-analysis found that while carer stress has a significant effect on subsequent institutionalisation of care recipients, the overall effect size was negligible (SMD=0·05, 95% CI=0·04–0·07). Sensitivity analyses found that, the effect size was higher for measurements of stress than for other measures, though still relatively small (SMD=0·23, 95% CI=0·09–0·38). Thus, whether analysing the association between carer stress, burden, distress, or depression with either acute or long-term care, the effect size remains small to negligible. Concurrently, we found estimates reduce over time and were smaller with larger studies and those of higher quality, according to the CCAT scores.Conclusion
Despite strong statements to the contrary, it appears that the effect of carer stress on subsequent care recipient institutionalisation is small to negligible. The current findings point to a biased literature, with significant small study effects. The results suggest a need to re-evaluate the degree to which carer stress predicts premature ending of home care. Concurrently, other factors may be more crucial in institutional placement than carer stress and should be investigated. 相似文献998.
Anish George Raghav T. Bhatia Gill L. Buchanan Anne Whiteside Robert S. Moisey Stephen F. Beer Sudipta Chattopadhyay Thozhukat Sathyapalan Joseph John 《PloS one》2015,10(11)
Objective
To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI).Research Design and Methods
Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on pre- discharge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE.Results
Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06–2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42–3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points.Conclusion
Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention. 相似文献999.
Bethany Levick Anne Laudisoit Liesbeth Wilschut Elisabeth Addink Vladimir Ageyev Aidyn Yeszhanov Valerij Sapozhnikov Alexander Belayev Tania Davydova Sally Eagle Mike Begon 《PloS one》2015,10(9)
Introduction
The wildlife plague system in the Pre-Balkhash desert of Kazakhstan has been a subject of study for many years. Much progress has been made in generating a method of predicting outbreaks of the disease (infection by the gram negative bacterium Yersinia pestis) but existing methods are not yet accurate enough to inform public health planning. The present study aimed to identify characteristics of individual mammalian host (Rhombomys opimus) burrows related to and potentially predictive of the presence of R.opimus and the dominant flea vectors (Xenopsylla spp.).Methods
Over four seasons, burrow characteristics, their current occupancy status, and flea and tick burden of the occupants were recorded in the field. A second data set was generated of long term occupancy trends by recording the occupancy status of specific burrows over multiple occasions. Generalised linear mixed models were constructed to identify potential burrow properties predictive of either occupancy or flea burden.Results
At the burrow level, it was identified that a burrow being occupied by Rhombomys, and remaining occupied, were both related to the characteristics of the sediment in which the burrow was constructed. The flea burden of Rhombomys in a burrow was found to be related to the tick burden. Further larger scale properties were also identified as being related to both Rhombomys and flea presence, including latitudinal position and the season.Conclusions
Therefore, in advancing our current predictions of plague in Kazakhstan, we must consider the landscape at this local level to increase our accuracy in predicting the dynamics of gerbil and flea populations. Furthermore this demonstrates that in other zoonotic systems, it may be useful to consider the distribution and location of suitable habitat for both host and vector species at this fine scale to accurately predict future epizootics. 相似文献1000.
Christopher P. Landowski Anne Huuskonen Ramon Wahl Ann Westerholm-Parvinen Anne Kanerva Anna-Liisa H?nninen Noora Salovuori Merja Penttil? Jari Natunen Christian Ostermeier Bernhard Helk Juhani Saarinen Markku Saloheimo 《PloS one》2015,10(8)
The filamentous fungus Trichoderma reesei has tremendous capability to secrete proteins. Therefore, it would be an excellent host for producing high levels of therapeutic proteins at low cost. Developing a filamentous fungus to produce sensitive therapeutic proteins requires that protease secretion is drastically reduced. We have identified 13 major secreted proteases that are related to degradation of therapeutic antibodies, interferon alpha 2b, and insulin like growth factor. The major proteases observed were aspartic, glutamic, subtilisin-like, and trypsin-like proteases. The seven most problematic proteases were sequentially removed from a strain to develop it for producing therapeutic proteins. After this the protease activity in the supernatant was dramatically reduced down to 4% of the original level based upon a casein substrate. When antibody was incubated in the six protease deletion strain supernatant, the heavy chain remained fully intact and no degradation products were observed. Interferon alpha 2b and insulin like growth factor were less stable in the same supernatant, but full length proteins remained when incubated overnight, in contrast to the original strain. As additional benefits, the multiple protease deletions have led to faster strain growth and higher levels of total protein in the culture supernatant. 相似文献