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991.
Aimee L. Cunningham Kim Minh Dang Jieh-Juen Yu M. Neal Guentzel Hans W. Heidner Karl E. Klose Bernard P. Arulanandam 《Vaccine》2014
Oral vaccination with the defined live attenuated Francisella novicida vaccine strain U112ΔiglB has been demonstrated to induce protective immunity against pulmonary challenge with the highly human virulent Francisella tularensis strain SCHU S4. However, this vaccination regimen requires a booster dose in mice and Exhibits 50% protective efficacy in the Fischer 344 rat model. To enhance the efficacy of this vaccine strain, we engineered U112ΔiglB to express the Salmonella typhimurium FljB flagellin D1 domain, a TLR5 agonist. The U112ΔiglB::fljB strain was highly attenuated for intracellular macrophage replication, and although the FljB protein was expressed within the cytosol, it exhibited TLR5 activation in a TLR5-expressing HEK cell line. Additionally, infection of splenocytes and lymphocytes with U112ΔiglB::fljB induced significantly greater TNF-α production than infection with U112ΔiglB. Oral vaccination with U112ΔiglB::fljB also induced significantly greater protection than U112ΔiglB against pulmonary SCHU S4 challenge in rats. The enhanced protection was accompanied by higher IgG2a production and serum-mediated reduction of Francisella infectivity. Thus, the U112ΔiglB::fljB strain may serve as a potential vaccine candidate against pneumonic tularemia. 相似文献
992.
Guillaume Fond Anderson Loundou Sebastien Guillaume Xavier Quantin Alexandra Macgregor Régis Lopez Philippe Courtet Paquito Bernard Daniel Bailly Mocrane Abbar Marion Leboyer Laurent Boyer 《European archives of psychiatry and clinical neuroscience》2014,264(5):379-389
It is unclear whether adult smokers with childhood attention-deficit/hyperactivity disorder history (CH) have more severe smoking behavior than non-CH smokers, while it is clearly suggested that CH adolescents have more severe smoking behavior than CH adolescents. The aim of the present comprehensive meta-analysis is to determine whether CH smokers have more severe smoking behavior characteristics than those without and the effect of age on the association between CH and smoking behavior. We included all case–control studies and first round data collection of observational studies addressing the difference in smoking behavior characteristics of CH smokers versus non-CH smokers, with validated scales or structured interviews, without any language or date restriction. Nine studies (including 365 smokers with CH and 1,708 smokers without) were included. Compared to non-CH smokers, CH smokers smoked significantly more cigarettes [standardized mean differences (SMD) = 0.15, 95 % CI 0.01–0.28, p = 0.04] and began to regularly smoke earlier (SMD = ?0.28, 95 % CI ?0.49; ?0.07, p = 0.01) but were not significantly more nicotine dependent (SMD = 0.23, 95 % CI ?0.04 to 0.48, p = 0.08). After removing the single adolescent study, the significant association between CH and number of daily smoked cigarettes disappeared, and subgroups analyses confirmed that the significant association between CH and number of daily smoked cigarettes disappeared as age increased. Our meta-analysis illustrates a clinically important link between CH and tobacco smoking in adolescence but not later in life. Further high-quality studies are needed to confirm this finding, as only two studies included participants with a mean age below 20 years. 相似文献
993.
Prejaas Tewarie Martijn D. Steenwijk Betty M. Tijms Marita Daams Lisanne J. Balk Cornelis J. Stam Bernard M.J. Uitdehaag Chris H. Polman Jeroen J.G. Geurts Frederik Barkhof Petra J.W. Pouwels Hugo Vrenken Arjan Hillebrand 《Human brain mapping》2014,35(12):5946-5961
Both gray matter atrophy and disruption of functional networks are important predictors for physical disability and cognitive impairment in multiple sclerosis (MS), yet their relationship is poorly understood. Graph theory provides a modality invariant framework to analyze patterns of gray matter morphology and functional coactivation. We investigated, how gray matter and functional networks were affected within the same MS sample and examined their interrelationship. Magnetic resonance imaging and magnetoencephalography (MEG) were performed in 102 MS patients and 42 healthy controls. Gray matter networks were computed at the group‐level based on cortical thickness correlations between 78 regions across subjects. MEG functional networks were computed at the subject level based on the phase‐lag index between time‐series of regions in source‐space. In MS patients, we found a more regular network organization for structural covariance networks and for functional networks in the theta band, whereas we found a more random network organization for functional networks in the alpha2 band. Correlation analysis revealed a positive association between covariation in thickness and functional connectivity in especially the theta band in MS patients, and these results could not be explained by simple regional gray matter thickness measurements. This study is a first multimodal graph analysis in a sample of MS patients, and our results suggest that a disruption of gray matter network topology is important to understand alterations in functional connectivity in MS as regional gray matter fails to take into account the inherent connectivity structure of the brain. Hum Brain Mapp 35:5946–5961, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
994.
Alireza Kashani Isabelle Thiffault Marie-Emmanuelle Dilenge Christine Saint-Martin Kether Guerrero Luan T. Tran Eric Shoubridge Marjo S. van der Knaap Nancy Braverman Geneviève Bernard 《Neurogenetics》2014,15(3):161-164
We report a case of mild cavitating leukoencephalopathy associated with a homozygous c.755A > G (p.Asp252Gly) NDUFS1 mutation in a 7-year old boy. Biochemical analysis confirmed an isolated reduction in complex I activity. Magnetic resonance imaging of the brain showed a diffuse cystic leukoencephalopathy with the involvement of the corpus callosum and sparing of the gray matter. The clinical course was marked by an acute presentation of neurological deficits at 24 months followed by recurrent episodes of mild neurological deterioration, subsequent remissions, and prolonged periods of stability. This is one of the mildest known clinical presentations of complex I deficiency secondary to mutations in NDUFS1, expanding the clinical spectrum and natural history of this disorder. Consideration of clinical variability needs to be taken into account in patient management and family counseling. 相似文献
995.
Mark S. Freedman Nicola De Stefano Frederik Barkhof Chris H. Polman Giancarlo Comi Bernard M. J. Uitdehaag Florence Casset-Semanaz Brian Hennessy Lorenz Lehr Bettina Stubinski Dominic L. Jack Ludwig Kappos 《Journal of neurology》2014,261(3):490-499
The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics (age, sex, use of steroids at the first event, classification of first event as mono- or multifocal, presence/absence of gadolinium-enhancing lesions, count of <9 or ≥9 T2 lesions), and by diagnosis of MS using the revised McDonald 2010 MS criteria. Patients were randomized to the serum-free formulation of IFN β-1a, 44 μg sc three times weekly or once weekly, or placebo, for 24 months or until diagnosis of CDMS. Treatment effects of sc IFN β-1a on McDonald 2005 MS and CDMS in the predefined subgroups were similar to effects found in the intent-to-treat population. McDonald 2010 MS was retrospectively diagnosed in 37.7 % of patients at baseline. Both regimens of sc IFN β-1a significantly reduced the risk versus placebo of McDonald 2005 MS and CDMS, irrespective of McDonald 2010 status at baseline (risk reductions between 29 and 51 %). The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics, or baseline presence/absence of McDonald 2010 MS. 相似文献
996.
Bertrand Vabres Yan Chérel David Minault Jérémy Hervouet Yvette Ducournau Anne Moreau Véronique Daguin Flora Coulon Annaïck Pallier Sophie Brouard Simon C. Robson Mark B. Nottle Peter J. Cowan Eric Venturi Pascal Mermillod Philippe Brachet Cesare Galli Irina Lagutina Roberto Duchi Jean‐Marie Bach Bernard Vanhove 《Xenotransplantation》2014,21(5):431-443
997.
Bernard T. Haylen Joseph Lee Chris Maher Jan Deprest Robert Freeman 《International urogynecology journal》2014,25(6):751-754
Introduction and hypothesis
Results of interobserver reliability studies for the International Urogynecological Association–International Continence Society (IUGA-ICS) Complication Classification coding can be greatly influenced by study design factors such as participant instruction, motivation, and test-question clarity. We attempted to optimize these factors.Methods
After a 15-min instructional lecture with eight clinical case examples (including images) and with classification/coding charts available, those clinicians attending an IUGA Surgical Complications workshop were presented with eight similar-style test cases over 10 min and asked to code them using the Category, Time and Site classification. Answers were compared to predetermined correct codes obtained by five instigators of the IUGA-ICS prostheses and grafts complications classification. Prelecture and postquiz participant confidence levels using a five-step Likert scale were assessed.Results
Complete sets of answers to the questions (24 codings) were provided by 34 respondents, only three of whom reported prior use of the charts. Average score [n (%)] out of eight, as well as median score (range) for each coding category were: (i) Category: 7.3 (91 %); 7 (4–8); (ii) Time: 7.8 (98 %); 7 (6–8); (iii) Site: 7.2 (90 %); 7 (5–8). Overall, the equivalent calculations (out of 24) were 22.3 (93 %) and 22 (18–24). Mean prelecture confidence was 1.37 (out of 5), rising to 3.85 postquiz. Urogynecologists had the highest correlation with correct coding, followed closely by fellows and general gynecologists.Conclusions
Optimizing training and study design can lead to excellent results for interobserver reliability of the IUGA-ICS Complication Classification coding, with increased participant confidence in complication-coding ability. 相似文献998.
999.
1000.
Agnès Garcias López Vasileios Bekiaris Katarzyna Müller Luda Julia Hütter Isabel Ulmert Konjit Getachew Muleta Joy Nakawesi Knut Kotarsky Bernard Malissen Meredith O'Keeffe Bernhard Holzmann William Winston Agace Katharina Lahl 《European journal of immunology》2020,50(10):1525-1536
Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF-α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches. 相似文献