19 research outputs found

    Aspirin therapy for cancer: It is never too late

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    Increased seroreactivity in tic disorder patients to a 60 kDa protein band from a neuronal cell line

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    In tic disorders, increased seroreactivity against neuronal antigens has been demonstrated, without performing molecular characterization of antigens. Here, unselected patients with a tic disorder were compared with healthy controls, autistic disorder (AD), and obsessive-compulsive disorder (OCD) patients. Seroreactivity against neuroblastoma cells was analyzed by Western blot. Anti-60 kDa binding occurred significantly more frequently in tic disorder patients (67.1%) than in AD (40.0%), OCD (40.0%) and healthy controls (41.9%). Sequence analysis of the 60 kDa protein band identified this as a ubiquitous heat shock protein. However, the involvement of other autoantigens with a molecular weight of 60 kDa cannot be excluded. (C) 2003 Elsevier B.V. All rights reserved

    Permeability of the windows of the brain: feasibility of dynamic contrast-enhanced MRI of the circumventricular organs

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    Abstract Background Circumventricular organs (CVOs) are small structures without a blood–brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood–brain barrier absence. Methods Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter. Results In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter. Conclusions Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures. Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-2

    Parent of origin effects on age at colorectal cancer diagnosis

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    Genomic imprinting refers to a parent-of-origin specific effect on gene expression. At least 1% of genes in the human genome are modulated in this manner. We sought evidence for genomic imprinting in colorectal cancer by studying the ages at diagnosis in the offspring of 2,061 parent-child pairs in which both parent and child were affected by nonsyndromic colorectal cancer. Families were ascertained through the colon Cancer Family Registry [http://epi.grants.cancer.gov/CFR/] from both population-based and clinic-based sources. We found that the affected offspring of affected fathers were on average younger than offspring of affected mothers (55.8 vs. 53.7 years; p = 0.0003), but when divided into sons and daughters, this difference was driven entirely by younger age at diagnosis in daughters of affected fathers compared to sons (52.3 years vs. 55.1 years; p = 0.0004). A younger age at diagnosis in affected daughters of affected fathers was also observable in various subsets including families that met Amsterdam II Criteria, families that did not meet Amsterdam Criteria, and in families with documented normal DNA mismatch repair in tumors. Imprinting effects are not expected to be affected by the sex of the offspring. Possible explanations for these unexpected findings include: (i) an imprinted gene on the pseudoautosomal regions of the X chromosome; (ii) an imprinted autosomal gene that affects a sex-specific pathway; or (iii) an X-linked gene unmasked because of colonic tissue-specific preferential inactivation of the maternal X chromosome.Noralane M. Lindor, Kari G. Rabe, Gloria M. Petersen, Helen Chen, Bharati Bapat, John Hopper, Joanne Young, Mark Jenkins, John Potter, Polly Newcomb, Allyson Templeton, Loic LeMarchand, John Grove, Michael R. Burgio, Robert Haile, Jane Green, Michael O. Woods, Daniela Seminara, Paul J. Limburg, and Stephen N. Thibodea

    Effects of the KEIGAAF intervention on the BMI z-score and energy balance-related behaviors of primary school-aged children

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    Abstract The aim of the current study was to evaluate the one- and two-year effectiveness of the KEIGAAF intervention, a school-based mutual adaptation intervention, on the BMI z-score (primary outcome), and energy balance-related behaviors (secondary outcomes) of children aged 7–10 years. A quasi-experimental study was conducted including eight intervention schools and three control schools located in low socioeconomic neighborhoods in the Netherlands. Baseline measurements were conducted in March and April 2017 and repeated after one and 2 years. Data were collected on children’s BMI z-score, sedentary behavior (SB), physical activity (PA) behavior, and nutrition behavior through the use of anthropometric measurements, accelerometers, and questionnaires, respectively. All data were supplemented with demographics, and weather conditions data was added to the PA data. Based on the comprehensiveness of implemented physical activities, intervention schools were divided into schools having a comprehensive PA approach and schools having a less comprehensive approach. Intervention effects on continuous outcomes were analyzed using multiple linear mixed models and on binary outcome measures using generalized estimating equations. Intervention and control schools were compared, as well as comprehensive PA schools, less comprehensive PA schools, and control schools. Effect sizes (Cohen’s d) were calculated. In total, 523 children participated. Children were on average 8.5 years old and 54% were girls. After 2 years, intervention children’s BMI z-score decreased (B = -0.05, 95% CI -0.11;0.01) significantly compared to the control group (B = 0.20, 95% CI 0.09;0.31). Additionally, the intervention prevented an age-related decline in moderate-to-vigorous PA (MVPA) (%MVPA: B = 0.95, 95% CI 0.13;1.76). Negative intervention effects were seen on sugar-sweetened beverages and water consumption at school, due to larger favorable changes in the control group compared to the intervention group. After 2 years, the comprehensive PA schools showed more favorable effects on BMI z-score, SB, and MVPA compared to the other two conditions. This study shows that the KEIGAAF intervention is effective in improving children’s MVPA during school days and BMI z-score, especially in vulnerable children. Additionally, we advocate the implementation of a comprehensive approach to promote a healthy weight status, to stimulate children’s PA levels, and to prevent children from spending excessive time on sedentary behaviors. Trial registration Netherlands Trial Register, NTR6716 ( NL6528 ), Registered 27 June 2017 – retrospectively registered
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