End stage renal disease (ESRD) is associated with defective T-cell mediated immunity. A diverse T-cell receptor (TCR) Vβ repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR Vβ repertoire was assessed.
Results
A higher proportion of ESRD patients (68.9 %) had a skewed TCR Vβ repertoire compared to age and cytomegalovirus (CMV) – IgG serostatus matched healthy individuals (31.4 %, P?<?0.001). Age, CMV serostatus and ESRD were independently associated with an increase in shifting of the TCR Vβ repertoire. More differentiated CD8+ T cells were observed in young ESRD patients with a shifted TCR Vβ repertoire. CD31-expressing naive T cells and relative telomere length of T cells were not significantly related to TCR Vβ skewing.
Conclusions
ESRD significantly skewed the TCR Vβ repertoire particularly in the elderly population, which may contribute to the uremia-associated defect in T-cell mediated immunity.
Polarimetric measurements in multiphoton microscopy can reveal information about the local molecular order of a sample. However, the presence of a dichroic through which the excitation beam propagates will generally scramble its polarization. We propose a simple scheme whereby a second properly‐oriented compensation dichroic is used to negate any alteration regardless of the wavelength and the initial polarization. We demonstrate how this robust and rapid approach simplifies polarimetric measurements in second‐harmonic generation, two‐photon excited fluorescence and coherent anti‐Stokes Raman scattering.
Illustration of the polarization maintaining strategy with the compensating dichroic oriented such that its s‐ and p‐axes are interchanged with these of the primary dichroic. 相似文献
IntroductionUpper limb evaluation of patients with Duchenne Muscular Dystrophy is crucially important to evaluations of efficacy of new treatments in non-ambulant patients. In patients who have lost ambulation, there are few validated and informative outcome measures. In addition, longitudinal data demonstrating sensitivity to clinical evolution of outcome measures over short-term periods are lacking.ResultsOur study confirmed preliminary data previously reported regarding feasibility of use and of reliability of the MyoSet and the correlation at baseline between distal strength and clinical outcomes such as FVC, Brooke score, age, and duration since loss of ambulation. A significant correlation was observed between the distal upper limb strength and clinical variables. The sensitive dynamometers (MyoGrip and MyoPinch) and MoviPlate captured a 12-month change in non-ambulant Duchenne muscular dystrophy patients of all ages.
Rehabilitation of animals followed by reintroduction into the wild can benefit conservation by supplementing depleted wild populations or reintroducing a species in an area where it has been extirpated or become extinct. The western lowland gorilla (WLG, Gorilla g. gorilla) is persistently poached; infants are often illegally traded and used as pets. Some are confiscated and rehabilitated, then kept in sanctuaries or reintroduced into the wild. Prior to reintroduction, the ability of the orphans to survive independently in their environment needs to be assessed. Here, we performed a multivariate analysis, including diet composition, activity-budget, and pattern of strata using of a group of five juvenile WLG in the process of rehabilitation and distinguished three sub-periods of ecological significance: the high furgivory period, the Dialium fruits consumption period, and the high folivory period. The consequences of these variations on their well-being (play behaviour) and the group cohesion (spatial proximity and social interactions) were examined. Like wild WLGs, diets shifted seasonally from frugivorous to folivorous, while the same staple foods were consumed and large amounts of Dialium fruits were seasonally gathered high in trees. When succulent fruit intake was the highest, thus providing high energy from sugar, juveniles spent less time feeding, more time playing and group cohesion was the highest. Conversely, the cohesion decreased with increasing folivory, individuals spent more time feeding and less time playing together. Nonetheless, the group cohesion also decreased after the death of one highly social, wild-born orphan. This may underscore the importance of skilled individuals in the cohesion and well-being of the entire group and, ultimately, to rehabilitation success. This study evaluates the rehabilitation success with regards to the methods used and highlights the need to consider a set of individual and environmental factors for enhancing rehabilitation while preserving the local biodiversity and individual well-being. 相似文献
Invasion of new territories by insect vector species that can transmit pathogens is one of the most important threats for human health. The spread of the mosquito Aedes albopictus in Europe is emblematic, because of its major role in the emergence and transmission of arboviruses such as dengue or chikungunya. Here, we modeled the spread of this mosquito species in France through a statistical framework taking advantage of a long-term surveillance dataset going back to the first observation of Ae. albopictus in the Metropolitan area. After validating the model, we show that human activities are especially important for mosquito dispersion while land use is a major factor for mosquito establishment. More importantly, we show that Ae. albopictus invasion is accelerating through time in this area, resulting in a geographic range extending further and further year after year. We also show that sporadic “jump” of Ae. albopictus in a new location far from the colonized area did not succeed in starting a new invasion front so far. Finally, we discuss on a potential adaptation to cooler climate and the risk of invasion into Northern latitudes. 相似文献
BackgroundIt is anticipated that current and future preventive therapies will likely be more effective in the early stages of dementia, when everyday functioning is not affected. Accordingly the early identification of people at risk is particularly important. In most cases, when subjects visit an expert and are examined using neuropsychological tests, the disease has already been developed. Contrary to this cognitive games are played by healthy, well functioning elderly people, subjects who should be monitored for early signs. Further advantages of cognitive games are their accessibility and their cost-effectiveness.PurposeThe aim of the investigation was to show that computer games can help to identify those who are at risk. In order to validate games analysis was completed which measured the correlations between results of the ''Find the Pairs'' memory game and the volumes of the temporal brain regions previously found to be good predictors of later cognitive decline.ResultsThere was a correlation between the number of attempts and the time required to complete the memory game and the volume of the entorhinal cortex, the temporal pole, and the hippocampus. There was also a correlation between the results of the Paired Associates Learning (PAL) test and the memory game.ConclusionsThe results gathered support the initial hypothesis that healthy elderly subjects achieving lower scores in the memory game have increased level of atrophy in the temporal brain structures and showed a decreased performance in the PAL test. Based on these results it can be concluded that memory games may be useful in early screening for cognitive decline. 相似文献
Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model.
Methods
First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG).
Results
Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4).
Conclusions
We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques. 相似文献
Despite the success of tamoxifen since its introduction, about one-third of patients with estrogen (ER) and/or progesterone receptor (PgR) - positive breast cancer (BC) do not benefit from therapy. Here, we aim to identify molecular mechanisms and protein biomarkers involved in tamoxifen resistance.
Results
Using iTRAQ and Immobilized pH gradient-isoelectric focusing (IPG-IEF) mass spectrometry based proteomics we compared tumors from 12 patients with early relapses (<2 years) and 12 responsive to therapy (relapse-free > 7 years). A panel of 13 proteins (TCEAL4, AZGP1, S100A10, ALDH6A1, AHNAK, FBP1, S100A4, HSP90AB1, PDXK, GFPT1, RAB21, MX1, CAPS) from the 3101 identified proteins, potentially separate relapse from non-relapse BC patients. The proteins in the panel are involved in processes such as calcium (Ca2+) signaling, metabolism, epithelial mesenchymal transition (EMT), metastasis and invasion. Validation of the highest expressed proteins in the relapse group identify high tumor levels of CAPS as predictive of tamoxifen response in a patient cohort receiving tamoxifen as only adjuvant therapy.
Conclusions
This data implicate CAPS in tamoxifen resistance and as a potential predictive marker.
Electronic supplementary material
The online version of this article (doi:10.1186/s12014-015-9080-y) contains supplementary material, which is available to authorized users. 相似文献
Foodborne diseases are globally important, resulting in considerable morbidity and mortality. Parasitic diseases often result in high burdens of disease in low and middle income countries and are frequently transmitted to humans via contaminated food. This study presents the first estimates of the global and regional human disease burden of 10 helminth diseases and toxoplasmosis that may be attributed to contaminated food.
Methods and Findings
Data were abstracted from 16 systematic reviews or similar studies published between 2010 and 2015; from 5 disease data bases accessed in 2015; and from 79 reports, 73 of which have been published since 2000, 4 published between 1995 and 2000 and 2 published in 1986 and 1981. These included reports from national surveillance systems, journal articles, and national estimates of foodborne diseases. These data were used to estimate the number of infections, sequelae, deaths, and Disability Adjusted Life Years (DALYs), by age and region for 2010. These parasitic diseases, resulted in 48.4 million cases (95% Uncertainty intervals [UI] of 43.4–79.0 million) and 59,724 (95% UI 48,017–83,616) deaths annually resulting in 8.78 million (95% UI 7.62–12.51 million) DALYs. We estimated that 48% (95% UI 38%-56%) of cases of these parasitic diseases were foodborne, resulting in 76% (95% UI 65%-81%) of the DALYs attributable to these diseases. Overall, foodborne parasitic disease, excluding enteric protozoa, caused an estimated 23.2 million (95% UI 18.2–38.1 million) cases and 45,927 (95% UI 34,763–59,933) deaths annually resulting in an estimated 6.64 million (95% UI 5.61–8.41 million) DALYs. Foodborne Ascaris infection (12.3 million cases, 95% UI 8.29–22.0 million) and foodborne toxoplasmosis (10.3 million cases, 95% UI 7.40–14.9 million) were the most common foodborne parasitic diseases. Human cysticercosis with 2.78 million DALYs (95% UI 2.14–3.61 million), foodborne trematodosis with 2.02 million DALYs (95% UI 1.65–2.48 million) and foodborne toxoplasmosis with 825,000 DALYs (95% UI 561,000–1.26 million) resulted in the highest burdens in terms of DALYs, mainly due to years lived with disability. Foodborne enteric protozoa, reported elsewhere, resulted in an additional 67.2 million illnesses or 492,000 DALYs. Major limitations of our study include often substantial data gaps that had to be filled by imputation and suffer from the uncertainties that surround such models. Due to resource limitations it was also not possible to consider all potentially foodborne parasites (for example Trypanosoma cruzi).
Conclusions
Parasites are frequently transmitted to humans through contaminated food. These estimates represent an important step forward in understanding the impact of foodborne diseases globally and regionally. The disease burden due to most foodborne parasites is highly focal and results in significant morbidity and mortality among vulnerable populations. 相似文献
