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991.
Andres Roman-Urrestarazu Päivi Lindholm Irma Moilanen Vesa Kiviniemi Jouko Miettunen Erika Jääskeläinen Pirjo Mäki Tuula Hurtig Hanna Ebeling Jennifer H. Barnett Juha Nikkinen John Suckling Peter B. Jones Juha Veijola Graham K. Murray 《European child & adolescent psychiatry》2016,25(5):529-538
When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnormalities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20–24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20–24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time. 相似文献
992.
Biomarkers in amyotrophic lateral sclerosis: combining metabolomic and clinical parameters to define disease progression
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993.
A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: a multicenter,randomized, placebo-controlled trial 总被引:13,自引:0,他引:13
Hyponatremia in advanced cirrhosis and ascites or congestive heart failure (CHF) is the result of an inappropriate increase in vasopressin secretion, which acts through activation of specific V(2) receptors in the distal renal nephron to increase water reabsorption. This study investigates the efficacy and safety of 3 different doses of the V(2) receptor antagonist, VPA-985, in correcting hyponatremia over a 7-day inpatient study period. Forty-four hospitalized patients (33 patients with cirrhosis, 6 with CHF, and 5 with syndrome of inappropriate antidiuretic hormone (SIADH) were studied on a constant sodium intake, with VPA doses of 25, 125, and 250 mg twice daily or placebo. Serum sodium measurements were repeated after every daily dose, and the next dose withheld for excessive serum sodium rises. Fluid intake was adjusted according to previous 24-hour urinary outputs. Adverse events were based on clinical signs of dehydration or encephalopathy. VPA-985 produced a significant overall aquaretic response compared with placebo, with significant dose related increases in free water clearance (P <.05) and serum sodium (P <.05), without significant changes in orthostatic blood pressure or serum creatinine levels. Five patients (50%) on 250 mg twice daily had to have medication withheld on multiple occasions. End-of-study plasma vasopressin levels increased significantly in the 2 larger dose groups. In conclusion, VPA-985 appears effective and safe in appropriate doses in correcting abnormal renal water handling and hyponatremia in conditions associated with water retention. Higher doses of VPA-985 may produce significant dehydration and will require close monitoring with their use. 相似文献
994.
Nastaran Meschi Mostafa EzEldeen Andres Eduardo Torres Garcia Reinhilde Jacobs Paul Lambrechts 《Journal of endodontics》2018,44(10):1517-1525
Introduction
A regenerative endodontic procedure (REP) is a biologically based treatment to functionally replace the pulp of infected immature permanent teeth. The purpose of this retrospective case series was to assess the outcome of REPs of infected immature permanent teeth in terms of periapical bone healing (PBH), root development (RD), and pulp vitality.Methods
Five patients (1 tooth/patient) who had undergone a REP based on the cell homing concept were recalled 3, 6, 12, 24, and 36 months postoperatively. At each recall session, clinical and periapical radiographic (PR) investigations were performed. Cone-beam computed tomographic (CBCT) imaging was taken before and 36 months after REPs. Qualitative and quantitative PR assessments were performed on the teeth that underwent REPs. Quantitative CBCT analyses were performed on the teeth that underwent REP and contralateral teeth.Results
At each recall session, all teeth were asymptomatic but reacted negatively on carbon dioxide snow and electrical pulp testing. All teeth that underwent a REP showed complete PBH and further RD on PR and CBCT assessments when comparing the baseline with the final recall radiographs. CBCT analyses indicated increases in root hard tissue volume and RL for all teeth that underwent a REP, but they were 5 and 3 times less, respectively, than the contralateral teeth. The postoperative CBCT images presented bone ingrowth inside the root canal, calcification, or nonuniform RD.Conclusions
Thirty-six months after the REPs (based on the cell homing concept), this RCS resulted radiographically and clinically in functional and asymptomatic teeth with complete PBH and continued reparative RD. CBCT quantitative measurements and qualitative root development observations are more reliable and accurate than PR analysis. 相似文献995.
Melinda E. Varney Madeline Niederkorn Hiroyasu Konno Takayuki Matsumura Jin Gohda Nobuaki Yoshida Taishin Akiyama Susanne Christie Jing Fang David Miller Andres Jerez Aly Karsan Jaroslaw P. Maciejewski Ruhikanta A. Meetei Jun-ichiro Inoue Daniel T. Starczynowski 《The Journal of experimental medicine》2015,212(11):1967-1985
TRAF-interacting protein with forkhead-associated domain B (TIFAB) is a haploinsufficient gene in del(5q) myelodysplastic syndrome (MDS). Deletion of Tifab results in progressive bone marrow (BM) and blood defects, including skewed hematopoietic stem/progenitor cell (HSPC) proportions and altered myeloid differentiation. A subset of mice transplanted with Tifab knockout (KO) HSPCs develop a BM failure with neutrophil dysplasia and cytopenia. In competitive transplants, Tifab KO HSPCs are out-competed by wild-type (WT) cells, suggesting a cell-intrinsic defect. Gene expression analysis of Tifab KO HSPCs identified dysregulation of immune-related signatures, and hypersensitivity to TLR4 stimulation. TIFAB forms a complex with TRAF6, a mediator of immune signaling, and reduces TRAF6 protein stability by a lysosome-dependent mechanism. In contrast, TIFAB loss increases TRAF6 protein and the dynamic range of TLR4 signaling, contributing to ineffective hematopoiesis. Moreover, combined deletion of TIFAB and miR-146a, two genes associated with del(5q) MDS/AML, results in a cooperative increase in TRAF6 expression and hematopoietic dysfunction. Re-expression of TIFAB in del(5q) MDS/AML cells results in attenuated TLR4 signaling and reduced viability. These findings underscore the importance of efficient regulation of innate immune/TRAF6 signaling within HSPCs by TIFAB, and its cooperation with miR-146a as it relates to the pathogenesis of hematopoietic malignancies, such as del(5q) MDS/AML.Myelodysplastic syndrome (MDS) refers to a group of hematopoietic stem cell (HSC) disorders associated with ineffective hematopoiesis, blood cytopenias, myeloid dysplasia, genomic instability, and predisposition to acute myeloid leukemia (AML) or bone marrow failure (BMF). Recent classifications of MDS describe eight subtypes based on biological, genetic, and morphological features (Cazzola and Malcovati, 2010). Independent of classification, MDS is propagated by rare and defective HSCs, and is defined by recurring cytogenetic changes and somatic point mutations. The most common cytogenetic alteration in MDS is deletion of chromosome (chr) 5q (del(5q)). In the absence of other cytogenetic alterations, MDS patients with a del(5q) exhibit refractory anemia, neutropenia, and elevated platelets associated with hypolobulated megakaryocytes (Giagounidis et al., 2006). Del(5q) is found in 25% of therapy-related MDS cases, which occur as a result of treatment with alkylating agents for unrelated conditions, and is strongly correlated with progression to AML (Haase et al., 2007; Haase, 2008; Qian et al., 2010). Although two commonly deleted regions (CDRs) have been mapped on chr 5q each spanning ∼1 Mb, a distal locus at 5q33.1, and a proximal locus at 5q31.1(Zhao et al., 1997), there are multiple genes that likely contribute to the pathogenesis of del(5q) MDS (Le Beau et al., 1989; Willman et al., 1993; Boultwood et al., 1994, 1997, 2000, 2002, 2007; Jaju et al., 1998). Clonal dominance of del(5q) cells is driven by haploid expression of CSNK1A1 (Schneider et al., 2014), whereas the erythroid defect has been attributed to RPS14 genes located within the distal CDR (Ebert et al., 2008; Barlow et al., 2010). Thrombocytosis associated with megakaryocytic dysplasia, neutropenia, and clonal dominance, are caused by loss of two miRNAs, miR-145 and miR-146a, in del(5q) MDS patients (Kumar et al., 2009; Starczynowski et al., 2010). Germline knockout of mouse miR-146a results in an early onset of myeloid expansion in the BM, and progression to more aggressive diseases such as lymphomas, BMF, and myeloid leukemia (Lu et al., 2010; Boldin et al., 2011; Zhao et al., 2011). Furthermore, overexpression of TRAF6, a miR-146a target gene, in mouse HSPCs mimics certain hematopoietic defects observed in miR-146a–deficient mice, including neutropenia, dysplasia, and myeloid leukemia. Overexpression of TRAF6, however, also results in elevated platelets. Some of the effects are mediated by IL-6, as overexpression of TRAF6 in Il6-deficient HSPCs restores platelets and neutrophil counts. DIAPH1, which encodes mDia1, is located on 5q31.3, which resides between the two commonly deleted regions in del(5q) MDS. mDia1-deficient mice exhibit an age-dependent granulocytopenia, and myeloid dysplasia in the BM, in part through increased TLR4 signaling. The proximal CDR at 5q31.1 is associated with aggressive forms of del(5q) and includes ∼12 coding genes. Two of these genes, CTNNA1 and EGR1, are thought to contribute to cell survival and myeloproliferation, respectively (Joslin et al., 2007; Liu et al., 2007). HSPA9 and PPP2CA have also been implicated in aspects of the del(5q) MDS/AML phenotype. Despite this recent progress, detailed molecular, cellular, and genetic analyses of candidate genes on chr 5q are required to completely understand the pathogenesis of del(5q) MDS/AML.Derepression of TRAF6, as a result of miR-146a haploinsufficiency, is one molecular consequence of del(5q) (Starczynowski et al., 2010; Boldin et al., 2011). TRAF6 is an E3 ubiquitin ligase and signal transducer of the innate immune signaling pathway in response to pathogens and host damage-associated molecules (Wu and Arron, 2003). A search of annotated genes within or near the CDR in del(5q) revealed a relatively uncharacterized gene, TRAF-interacting protein with forkhead-associated domain B (TIFAB). TIFAB resides within the proximal CDR on band 5q31.1, and belongs to a family of forkhead-associated domain proteins that also includes TIFA. TIFA was originally identified as a TRAF6-interacting protein in a yeast two-hybrid screen (Kanamori et al., 2002; Takatsuna et al., 2003), whereas TIFAB was identified as a TIFA-related protein by an in silico homology screen (Matsumura et al., 2004, 2009). To investigate whether loss of TIFAB is important to the pathophysiology of del(5q) MDS/AML, in this study, we characterized a germline Tifab knockout (KO) mouse. Tifab−/− mice exhibit progressive hematopoietic defects, including skewed HSPC proportions, altered myeloid differentiation, and a BMF-like disease associated with BM dysplasia and cytopenia. Tifab−/− BM cells are hypersensitive to Toll-like receptor 4 (TLR4) stimulation, suggesting that loss of TIFAB alters the innate immune pathway. Independent of TRAF6 mRNA, TIFAB loss results in stabilization of TRAF6 protein. Moreover, combined deletion of TIFAB and miR-146a results in a cooperative increase in TRAF6 expression and hematopoietic dysfunction in vivo. This provides a potential molecular explanation for altered TLR4 sensitivity and the BMF phenotype. Collectively, our results provide evidence that deletion of TIFAB contributes to an MDS-like hematopoietic phenotype in mice by changing the dynamic range of the innate immune pathway in HSPCs through the regulation of TRAF6 protein stability. 相似文献
996.
997.
998.
Larissa Marinho AZEVEDO Leslie Carol CASAS-APAYCO Carlos Andres VILLAVICENCIO ESPINOZA Linda WANG Maria Fidela de Lima NAVARRO Maria Teresa ATTA 《Journal of applied oral science : revista FOB》2015,23(3):315-320
Interface integrity can be maintained by setting the composite in a layering technique and using liners.
Objective
The aim of this in vitro study was to verify the effect of resin-modified glass-ionomer cement (RMGIC) lining and composite layering technique on the bond strength of the dentin/resin adhesive interface of lateral walls of occlusal restorations.Material and Methods
Occlusal cavities were prepared in 52 extracted sound human molars, randomly assigned into 4 groups: Group 2H (control) – no lining + two horizontal layers; Group 4O: no lining + four oblique layers; Group V-2H: RMGIC lining (Vitrebond) + two horizontal layers; and Group V-4O: RMGIC lining (Vitrebond) + four oblique layers. Resin composite (Filtek Z250, 3M ESPE) was placed after application of an adhesive system (Adper™ Single Bond 2, 3M ESPE) dyed with a fluorescent reagent (Rhodamine B) to allow confocal microscopy analysis. The teeth were stored in deionized water at 37oC for 24 hours before being sectioned into 0.8 mm slices. One slice of each tooth was randomly selected for Confocal Laser Scanning Microscopy (CLSM) analysis. The other slices were sectioned into 0.8 mm x 0.8 mm sticks to microtensile bond strength test (MPa). Data were analyzed by two-way ANOVA and Fisher’s test.Results
There was no statistical difference on bond strength among groups (p>0.05). CLSM analysis showed no significant statistical difference regarding the presence of gap at the interface dentin/resin among groups.Conclusions
RMGIC lining and composite layering techniques showed no effect on the microtensile bond strength and gap formation at the adhesive interface of lateral walls of high C-factor occlusal restorations. 相似文献999.
Emilio Andres Buschiazzo Emilce Edith Schneeberger Fernando Andres Sommerfleck Cesar Ledesma Gustavo Citera 《Clinical rheumatology》2016,35(9):2229-2233
Some reports describe an increased mortality in patients with ankylosing spondylitis (AS) compared to the general population. The aims of this study were to evaluate the cumulative survival in patients with AS and to establish possible factors associated with mortality. In cross-sectional retrospective study, AS patients were included according to 1984 modified NY criteria, in the 2000–2010 period, the prevalence of mortality was determined by review of medical records, telephone contact, family reports, and death certificates, and it was compared with mortality in Argentina’s general population. One hundred twenty-seven patients were studied, 96 (75.6 %) were male, median age 49 years (interquartile range (IQR) 34–60) and median disease duration 8 years (IQR 4–17). During the follow-up period, 9 patients died (7.1 %). The median estimated survival from diagnosis of AS was 39 years (IQR 34–50) and median cumulative survival was 76 years (IQR 74–85). Cardiovascular disease was the most frequent cause of death (5/9 patients). Deceased patients had a mean age and a mean AS disease duration significantly higher than living patients (68.1?±?12.4 years vs 46.4?±?15.09 years, p?=?0.0001 and 33?±?13.7 years vs 12?±?10.7 years, p?=?0.001, respectively), higher frequency of total surgeries [3/5 (60 %) vs 5/105 (4.76 %), p?=?0.002] and cauda equina syndrome [3/6 (50 %) vs 2/116 (1.72 %), p?=?0.001], respectively. Frequency of mortality in AS patients was higher than the crude mortality rate of Argentina’s general population in the same period, with cardiovascular cause being the most frequent one. 相似文献
1000.
Blockade of CD40–TRAF2,3 or CD40–TRAF6 is sufficient to inhibit pro‐inflammatory responses in non‐haematopoietic cells
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Jose‐Andres C. Portillo Jennifer A. Greene Isaac Schwartz Maria Cecilia Subauste Carlos S. Subauste 《Immunology》2015,144(1):21-33
Inhibition of the CD40–CD154 pathway controls inflammatory disorders. Unfortunately, administration of anti‐CD154 monoclonal antibodies causes thromboembolism. Blockade of signalling downstream of CD40 may represent an approach to treat CD40‐driven inflammatory disorders. Blocking tumour necrosis factor receptor‐associated factor 6 (TRAF6) signalling downstream of CD40 in MHC II+ cells diminishes inflammation. However, CD40–TRAF6 blockade may cause immunosuppression. We examined the role of CD40–TRAF2,3 and CD40–TRAF6 signalling in the development of pro‐inflammatory responses in human non‐haematopoietic and monocytic cells. Human aortic endothelial cells, aortic smooth muscle cells, renal proximal tubule epithelial cells, renal mesangial cells and monocytic cells were transduced with retroviral vectors that encode wild‐type CD40, CD40 with a mutation that prevents TRAF2,3 recruitment (ΔT2,3), TRAF6 recruitment (ΔT6) or both TRAF2,3 plus TRAF6 recruitment (ΔT2,3,6). Non‐haematopoietic cells that expressed CD40 ΔT2,3 exhibited marked inhibition in CD154‐induced up‐regulation of vascular cell adhesion molecule 1, intercellular adhesion molecule 1 (ICAM‐1), monocyte chemotactic protein 1 (MCP‐1), tissue factor and matrix metalloproteinase 9. Similar results were obtained with cells that expressed CD40 ΔT6. Although both mutations impaired ICAM‐1 up‐regulation in monocytic cells, only expression of CD40 ΔT6 reduced MCP‐1 and tissue factor up‐regulation in these cells. Treatment of endothelial and smooth muscle cells with cell‐permeable peptides that block CD40–TRAF2,3 or CD40–TRAF6 signalling impaired pro‐inflammatory responses. In contrast, while the CD40–TRAF2,3 blocking peptide did not reduce CD154‐induced dendritic cell maturation, the CD40–TRAF6 blocking peptide impaired this response. Hence, preventing CD40–TRAF2,3 or CD40–TRAF6 interaction inhibits pro‐inflammatory responses in human non‐haematopoietic cells. In contrast to inhibition of CD40–TRAF6 signalling, inhibition of CD40–TRAF2,3 signalling did not impair dendritic cell maturation. Blocking CD40–TRAF2,3 signalling may control CD40–CD154‐dependent inflammatory disorders. 相似文献