Background: In this report we describe, for the first time, the activation of the peripheral immune compartment in a patient with a CRB1 linked retinal degenerative disease, masquerading as intermediate uveitis.
Methods: To monitor the immune system during systemic immunosuppressive treatment, given for the initial diagnosis of intermediate uveitis, blood samples were taken before and during therapy, for analysis of peripheral blood mononuclear cell-subsets and circulating immune mediators.
Results: The levels of various pro-inflammatory immune mediators (including MIF, TSLP, CCL2/MCP-1, CXCL9, CXCL10, IFN-β, IL-6, IL-17, IL-21, IL-22, and IL-23) were elevated in serum at the first time point, and decreased under immunosuppressive treatment. In parallel, the frequency of activated (CD86+) CD1c+ myeloid dendritic cells in blood was proportional to the central foveal thickness measured by optical coherence tomography.
Conclusions: These observations challenge the current view on the distinct pathophysiology of retinal degenerative and retinal inflammatory conditions in this patient. 相似文献
Rho GTPases are small proteins that act as binary molecular switches in a wide range of signalling pathways upon stimulation of cell surface receptors. Three different classes of regulatory proteins control their activity. In the activated state small GTPases are able to bind a variety of effector proteins and initiate downstream signalling. Rho GTPases regulate important cellular processes ranging from cytoskeletal remodelling and gene expression to cell proliferation and membrane trafficking. Therefore it is not surprising that deregulated Rho signalling can contribute to disturbed cellular phenotypes in a wide range of diseases. The main focus of this review will be the diversity of functions of Rho GTPases and the effects of aberrant Rho GTPase signalling in various aspects of cancer. 相似文献
Pigs have been suggested to be a potential reservoir for locally acquired human hepatitis E virus (HEV) infections in the Netherlands. To study possible trends in HEV prevalence in the Dutch pig population, 97 pig farms have been screened for the presence of HEV in stools. The prevalence rate of HEV was estimated at 55% (53/97) in 2005, indicating a significant increase as compared to the prevalence rate of 22% (25/115) as was reported in 1999. The current data suggest that this increase is due to the inclusion of appropriate quality assurance controls such as internal amplification controls for RT-PCR. The abundant presence of pigs excreting HEV raises concerns on potential zoonotic transmission of the virus, either by exposure through the environment or by consumption of contaminated pork products. Moreover, one of the detected strains belonged to a European cluster which was not detected in the Netherlands before, suggesting that HEV strains spread through European countries. These data demonstrate the need to include appropriate controls in diagnostic assays, especially in complex matrices such as feces which are known to contain PCR inhibitory substances. 相似文献
BACKGROUND: Exhaled breath contains thousands of volatile organic compounds (VOCs) that could serve as biomarkers of lung disease. Electronic noses can distinguish VOC mixtures by pattern recognition. OBJECTIVE: We hypothesized that an electronic nose can discriminate exhaled air of patients with asthma from healthy controls, and between patients with different disease severities. METHODS: Ten young patients with mild asthma (25.1 +/- 5.9 years; FEV(1), 99.9 +/- 7.7% predicted), 10 young controls (26.8 +/- 6.4 years; FEV(1), 101.9 +/- 10.3), 10 older patients with severe asthma (49.5 +/- 12.0 years; FEV(1), 62.3 +/- 23.6), and 10 older controls (57.3 +/- 7.1 years; FEV(1), 108.3 +/- 14.7) joined a cross-sectional study with duplicate sampling of exhaled breath with an interval of 2 to 5 minutes. Subjects inspired VOC-filtered air by tidal breathing for 5 minutes, and a single expiratory vital capacity was collected into a Tedlar bag that was sampled by electronic nose (Cyranose 320) within 10 minutes. Smellprints were analyzed by linear discriminant analysis on principal component reduction. Cross-validation values (CVVs) were calculated. RESULTS: Smellprints of patients with mild asthma were fully separated from young controls (CVV, 100%; Mahalanobis distance [M-distance], 5.32), and patients with severe asthma could be distinguished from old controls (CVV, 90%; M-distance, 2.77). Patients with mild and severe asthma could be less well discriminated (CVV, 65%; M-distance, 1.23), whereas the 2 control groups were indistinguishable (CVV, 50%; M-distance, 1.56). The duplicate samples replicated these results. CONCLUSION: An electronic nose can discriminate exhaled breath of patients with asthma from controls but is less accurate in distinguishing asthma severities. CLINICAL IMPLICATION: These findings warrant validation of electronic noses in diagnosing newly presented patients with asthma. 相似文献
We studied the association between the short/long promotor-based length polymorphism of the serotonin transporter gene (5-HTTLPR)
and neuroticism, anxiety and depression. Subjects included twins, their siblings and parents from the Netherlands Twin Register
(559 parents and 1,245 offspring). Subjects had participated between one and five times in a survey study measuring neuroticism,
anxiety and depression. Offspring of these families were also approached to participate in a psychiatric interview diagnosing
DSM-IV major depression. Within-family and total association between 5-HTTLPR and these traits were tested. Only three of
the 36 tests showed a significant effect of 5-HTTLPR (P < 0.05). These effects were in opposite directions, i.e. both negative and positive regression coefficients were found for
the s allele. No additive effect of the s allele was found for DSM-IV depression. Our results strongly suggest that there is no straightforward association between
5-HTTLPR and neuroticism, anxiety and depression.
Edited by Stacey Cherny 相似文献
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die Ausbreitung von Antibiotikaresistenzen wurde in den letzten Jahren zunehmend als Problem im Bereich globale Gesundheit... 相似文献
Hospitalizations and lower limb amputations related to diabetes mellitus (DM) are considered to be potentially avoidable. Appropriate outpatient care of diabetes prevents complications. Rates on potentially avoidable hospitalizations for diabetes are core indicators of the German diabetes surveillance program. International comparisons showed high hospitalization rates in Germany for both indicators.
Objectives
The objective of this analysis is to describe time trends on hospitalizations and inpatient lower limb amputations (major amputations) for DM. Furthermore, we analyze small area variations.
Materials and methods
Based on the German diagnosis related groups (DRGs) dataset we calculated age-standardized rates covering 2005–2015. Calculations rely on the Organisation for Economic Co-operation and Development (OECD) indicator definitions. Time trends are obtained by linear regression modelling. We also stratified into age groups and analyzed 2015 small-area variations using age-adjusted rates.
Results
Crude hospitalization rates were 310 admissions per 100,000 inhabitants in men (amputation rate: 15.6) and 216 admissions per 100,000 inhabitants in women (amputation rate: 7.1) in 2015. Age-adjusted hospitalizations and amputations rates in women decreased over time (10.3 and 1.2 cases per 100,000 inhabitants and year, respectively). In men, the amputation rate decreased significantly (1.5 cases per 100,000 inhabitants and year). We found higher rates for men than for women in almost all age categories. In eastern Germany and parts of Bavaria and North Rhine-Westphalia rates are particularly high.
Conclusions
A decrease in hospitalization rates may indicate improvements in ambulatory diabetes care over time. Future studies should consider age-specific differences and small-area variations.
When proven effective, decision making regarding reimbursement of new health technology typically involves ethical, social, legal, and health economic aspects and constraints. Nevertheless, when applying standard value of information (VOI) analysis, the value of collecting additional evidence is typically estimated assuming that only cost-effectiveness outcomes guide such decisions.
Objectives
To illustrate how decision makers’ constraints can be incorporated into VOI analyses and how these may influence VOI outcomes.
Methods
A simulation study was performed to estimate the cost-effectiveness of a new hypothetical technology compared with usual care. Constraints were defined for the new technology on 1) the maximum acceptable rate of complications and 2) the maximum acceptable additional budget. The expected value of perfect information (EVPI) for the new technology was estimated in various scenarios, both with and without incorporating these constraints.
Results
For a willingness-to-pay threshold of €20,000 per quality-adjusted life-year, the probability that the new technology was cost-effective equaled 57%, with an EVPI of €1868 per patient. Applying the complication rate constraint reduced the EVPI to €1137. Similarly, the EVPI reduced to €770 when applying the budget constraint. Applying both constraints simultaneously further reduced the EVPI to €318.
Conclusions
When decision makers explicitly apply additional constraints, beyond a willingness-to-pay threshold, to reimbursement decisions, these constraints can and should be incorporated into VOI analysis as well, because they may influence VOI outcomes. This requires continuous interaction between VOI analysts and decision makers and is expected to improve both the relevance and the acceptance of VOI outcomes. 相似文献