Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands cohort study on diet and cancer

Sporadic colorectal cancer (CRC) is characterized by genetic and epigenetic changes such as regional DNA hypermethylation and global DNA hypomethylation. Epidemiological and animal studies suggest that aberrant DNA methylation is associated with low dietary folate intake, which is aggravated by high alcohol intake. The relationship between promoter methylation of genes involved in CRC carcinogenesis and folate and alcohol intake was investigated. Methylation of the APC-1A, p14(ARF), p16(INK4A), hMLH1, O(6)-MGMT, and RASSF1A promoters was studied using methylation-specific PCR in 122 sporadic CRCs, derived from patients with folate and alcohol intake at either the lower or the higher quintiles of the distribution. Overall, promoter hypermethylation frequencies observed were: 39% for APC; 33% for p14(ARF); 31% for p16(INK4A); 29% for hMLH1; 41% for O(6)-MGMT; and 20% for RASSF1A. For each of the tested genes, the prevalence of promoter hypermethylation was higher in CRCs derived from patients with low folate/high alcohol intake (n = 61) when compared with CRCs from patients with high folate/low alcohol intake (n = 61), but the differences were not statistically significant. The number of CRCs with at least one gene methylated was higher (84%) in the low folate intake/high alcohol intake group when compared with the high folate intake/low alcohol intake group (70%; P = 0.085). Despite the size limitations of this study, these data suggest that folate and alcohol intake may be associated with changes in promoter hypermethylation in CRC.     

Enhanced pitch sensitivity in individuals with autism: a signal detection analysis

Past research has shown a superiority of participants with high-functioning autism over comparison groups in memorizing picture-pitch associations and in detecting pitch changes in melodies. A subset of individuals with autism, known as "musical savants," is also known to possess absolute pitch. This superiority might be due to an abnormally high sensitivity to fine-grained pitch differences in sounds. To test this hypothesis, psychoacoustic tasks were devised so as to use a signal detection methodology. Participants were all musically untrained and were divided into a group of 12 high-functioning individuals with autism and a group of 12 normally developing individuals. Their task was to judge the pitch of pure tones in a "same-different" discrimination task and in a "high-low" categorization task. In both tasks, the obtained psychometric functions revealed higher pitch sensitivity for subjects with autism, with a more pronounced advantage over control participants in the categorization task. These findings confirm that pitch processing is enhanced in "high-functioning" autism. Superior performance in pitch discrimination and categorization extends previous findings of enhanced visual performance to the auditory domain. Thus, and as predicted by the enhanced perceptual functioning model for peaks of ability in autism (Mottron & Burack, 2001), autistic individuals outperform typically developing population in a variety of low-level perceptual tasks.     

Impact of birth weight and genetic liability on psychopathology in children of bipolar parents

OBJECTIVE: To test different models for ways in which birth weight and familial loading influence the risk for psychopathology in bipolar offspring. METHOD: DSM-IV diagnoses of 140 bipolar offspring (12-21 years of age) were assessed with the K-SADS-PL. Parents were interviewed using the Family History-Research Diagnostic Criteria to determine familial loading of mood and substance use disorders. Parents reported the birth weight of their offspring. Age- and sex-adjusted hazard ratios were calculated. RESULTS: Low birth weight was associated with mood and non-mood disorders in bipolar offspring (hazard ratio = 0.6, confidence interval = 0.4-0.8), even after controlling for familial loading of unipolar disorder, bipolar disorder, or substance use disorder. There were no significant interactions between birth weight and familial loading of unipolar disorder, familial loading of bipolar disorder, and familial loading of substance use disorder. CONCLUSIONS: Birth weight is associated with mood as well as non-mood disorders. This association is independent from the association of familial loading of mood and substance use disorder with mood- and non-mood disorders in bipolar offspring.     

Cardio-metabolic risk in 5-year-old children prenatally exposed to maternal psychosocial stress: the ABCD study

Background  

Recent evidence, both animal and human, suggests that modifiable factors during fetal and infant development predispose for cardiovascular disease in adult life and that they may become possible future targets for prevention. One of these factors is maternal psychosocial stress, but so far, few prospective studies have been able to investigate the longer-term effects of stress in detail, i.e. effects in childhood. Therefore, our general aim is to study whether prenatal maternal psychosocial stress is associated with an adverse cardio-metabolic risk profile in the child at age five.     

SDS-PAGE analysis of protein and lipopolysaccharide of extracellular vesicules and Sarkosyl-insoluble membranes from Bacteroides gingivalis

We have compared outer membranes (OM) of Bacteroides gingivalis ATCC 33277 isolated by the following 3 techniques: 1) high speed centrifugation after mechanical cell shearing; 2) sonication of the bacteria, followed by solubilization of the cytoplasmic membrane with N-Laurylsarconsinate (Sarkosyl), after which the Sarkosyl-insoluble membranes were recovered by centrifugation; 3) ammonium sulfate precipitation of extracellular vesicules from culture supernatant, followed by centrifugation and dialysis. Electron microscopy showed that the 3 preparations consisted of closed vesicules. Analysis by SDS-PAGE revealed that all 3 contained up to 28 polypeptides, most of which were common to each extract. The extracellular vesicules and Sarkosyl-insoluble preparation yielded similar protein patterns, although quantitative differences were observed. The sheared-cell preparation contained 8 additional proteins. The level of contamination of OM material by peptidoglycan and cytosol components was 1.8% in the sheared-cell preparation, and was null or lower than 0.8% in the other preparations. All 3 preparations showed the presence of LPS with a multiple banding pattern typical of smooth LPS. The sheared-cell preparation had a slightly lower LPS content than the other 2 preparations. Since extracellular vesicules are naturally released during bacterial growth, and are relatively simple to obtain, such native entities seem an appropriate source of OM components for use in studying the immunobiology of B. gingivalis surface antigens.     

Improvement in the routine screening performance of cytotechnologists over time

BACKGROUND:

Documenting the performance of gynecologic screening in actual practice settings is difficult to achieve. In the current study, the screening performance of 11 individual cytotechnologists as well as that of the overall laboratory over 2 consecutive time periods was examined using the rapid prescreening (RPS) method.

METHODS:

RPS was performed by all cytotechnologists in a single laboratory over 2 separate 8‐month periods. The sensitivity of screening for individual and groups of cytotechnologists was examined. For purposes of comparison, cytotechnologists were divided into 2 groups: screeners with an overall routine sensitivity ≥95% and screeners with an overall sensitivity <95%.

RESULTS:

Atypical squamous cells (ASC) were used as a threshold, and routine screening sensitivity was found to vary from 68.3% to 96.8%. The overall sensitivity of the laboratory for RPS and routine screening was 43.6% and 88.4%, respectively. Over time, the overall laboratory sensitivity of routine screening improved from 85.3% to 91.3% (P = .01). During this same time frame, the sensitivity of the screeners with an overall sensitivity <95% improved from 79.3% to 91.2% (P < .001), whereas the sensitivity of screeners with an overall routine sensitivity ≥95% remained the same (96.1% to 96.4%; P = .6).

CONCLUSIONS:

In addition to improved overall performance of the laboratory by detecting and correcting errors, the results of the current study indicate that using RPS consistently over time might play a role leading to improved performance of cytotechnologists with an overall routine sensitivity <95% but not of cytotechnologists with an overall routine sensitivity ≥95%. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

CFTR rescue with VX-809 and VX-770 favors the repair of primary airway epithelial cell cultures from patients with class II mutations in the presence of Pseudomonas aeruginosa exoproducts

Background

Progressive airway damage due to bacterial infections, especially with Pseudomonas aeruginosa remains the first cause of morbidity and mortality in CF patients. Our previous work revealed a repair delay in CF airway epithelia compared to non-CF. This delay was partially prevented after CFTR correction (with VRT-325) in the absence of infection. Our goals were now to evaluate the effect of the Orkambi combination (CFTR VX-809 corrector?+?VX-770 potentiator) on the repair of CF primary airway epithelia, in infectious conditions.

Pain-related psychological issues in hand therapy

Study Design

Literature review.

Differentiation of MSC and annulus fibrosus cells on genetically engineered silk fleece‐membrane‐composites enriched for GDF‐6 or TGF‐β3

Intervertebral disc (IVD) repair is a high‐priority topic in our active and increasingly ageing society. Since a high number of people are affected by low back pain treatment options that are able to restore the biological function of the IVD are highly warranted. Here, we investigated whether the feasibility of genetically engineered (GE)‐silk from Bombyx mori containing specific growth factors to precondition human bone‐marrow derived mesenchymal stem cells (hMSC) or to activate differentiated human annulus fibrosus cells (hAFC) prior transplantation or for direct repair on the IVD. Here, we tested the hypothesis that GE‐silk fleece can thrive human hMSC towards an IVD‐like phenotype. We aimed to demonstrate a possible translational application of good manufacturing practice (GMP)‐compliant GE‐silk scaffolds in IVD repair and regeneration. GE‐silk with growth and differentiation factor 6 (GDF‐6‐silk) or transforming growth factor β3 (TGF‐β3, TGF‐β3‐silk) and untreated silk (cSilk) were investigated by DNA content, cell activity assay and glycosaminoglycan (GAG) content and their differentiation potential by qPCR analysis. We found that all silk types demonstrated a very high biocompatibility for both cell types, that is, hMSC and hAFC, as revealed by cell activity, and DNA proliferation assay. Further, analyzing qPCR of marker genes revealed a trend to differentiation toward an NP‐like phenotype looking at the Aggrecan/Collagen 2 ratio which was around 10:1. Our results support the conclusion that our GE‐silk scaffold treatment approach can thrive hMSC towards a more IVD‐like phenotype or can maintain the phenotype of native hAFC. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1324–1333, 2018.