Eliminating Age Differences in Children’s and Adults’ Suggestibility and Memory Conformity Effects

We examined whether typical developmental trends in suggestion-induced false memories (i.e., age-related decrease) could be changed. Using theoretical principles from the spontaneous false memory field, we adapted two often-used false memory procedures: misinformation (Experiment 1) and memory conformity (Experiment 2). In Experiment 1, 7/9-year old children (n = 33) and adults (n = 39) received stories containing associatively-related details. They then listened to misinformation in the form of short narrative preserving the meaning of the story. Children and adults were equally susceptible to the misinformation effect. In Experiment 2, younger (7/8-yearolds, n = 30) and older (11/12-year-olds, n = 30) children and adults (n = 30) viewed pictures containing associatively-related details. They viewed these pictures in pairs. Although the pictures differed, participants believed they had viewed the same pictures. Participants had to report what they could recollect during collaborative and individual recall tests. Children and adults were equally susceptible to memory conformity effects. When correcting for response bias, adults’ false memory scores were even higher than children’s. Our results show that age trends in suggestion-induced false memories are not developmentally invariant

Роми України і Миколаївщини

У статті розглянуто історію появи ромів на території України. Наприкінці ХVIII ст. 9-а ревізія виявила ромськенаселення уХерсонськійгубернії (територія сучасної Миколаївщини). Зараз у цьому регіоні проживає понад 1500 ромів.В статье рассмотрена история появления ромов на территории Украины. В конце ХVIII ст. 9-я ревизия зафиксировала наличие цыганского населения в Херсонской губернии (территория современной Николаевщины). Сейчас в этом регионе проживает более 1500 ромов.History of appearance of Romanies on the territory of Ukraine is considered in the thesis. At the end of 18th century Romanies are fixed in the 9th revision on the territory of Kherson province (modern Mykolaiv region). There are more than 1500 Romanies in this region now

Targeted enrichment of genomic DNA regions for next-generation sequencing

In this review, we discuss the latest targeted enrichment methods and aspects of their utilization along with second-generation sequencing for complex genome analysis. In doing so, we provide an overview of issues involved in detecting genetic variation, for which targeted enrichment has become a powerful tool. We explain how targeted enrichment for next-generation sequencing has made great progress in terms of methodology, ease of use and applicability, but emphasize the remaining challenges such as the lack of even coverage across targeted regions. Costs are also considered versus the alternative of whole-genome sequencing which is becoming ever more affordable. We conclude that targeted enrichment is likely to be the most economical option for many years to come in a range of settings

THE USE OF SANDWICH-CULTURED RAT HEPATOCYTES TO DETERMINE THE INTRINSIC CLEARANCE OF COMPOUNDS WITH DIFFERENT EXTRACTION RATIOS: 7-ETHOXYCOUMARIN AND WARFARIN

ABSTRACT: The application of sandwich-cultured rat hepatocytes for the identification of the hepatic intrinsic clearance of compounds with widely varying extraction ratios was investigated. We previously showed the applicability of this in vitro system, in combination with a model describing molecular diffusion, hepatocyte/medium partition, and nonsaturated metabolism, which resulted in a successful identification of this parameter for tolbutamide. This approach is further validated using the compounds 7-ethoxycoumarin and warfarin, covering a 100-fold range of extraction ratios. Clearance of these two substrates could be reliably determined, but only if the depletion of the parent compound in medium as well as in the hepatocyte sandwich was measured. Sensitivity analyses showed that the time course of depletion of the parent compound in medium, especially for warfarin, is insensitive to the partition and diffusion parameter values, whereas depletion in the hepatocyte sandwich was far more sensitive. When varying the volumes of collagen in the sandwich culture, it appears that the most reliable kinetic parameters could be obtained by fitting the data with the smaller collagen volume and that these parameters obtained from fitting to data of the larger volumes generally cannot be verified satisfactorily with the data of the smaller volumes. The values of hepatic clearance that were obtained after extrapolation of the intrinsic clearance to the hepatic clearance from blood were comparable within a factor of 2 to hepatic clearance data in the literature. This indicates that this sandwich culture and modeling system can be applied for the identification of the hepatic intrinsic clearance rate of the total range from low to high clearance compounds. Predicting the kinetic parameters of compounds in vivo using data from in vitro experiments is a fast developing area of research Recently, we have successfully developed the alternative approach of using sandwich-cultured rat hepatocytes in determining the in vitro intrinsic clearance of the slowly metabolized compound tolbutamide In this alternative approach, the use of data on substrate depletion was chosen rather than the use of data on metabolite formation. Using data on metabolite formation may cause practical problems when analytical methods or standards to study the kinetics of metabolite Article, publication date, and citation information can be found at http://dmd.aspetjournals.org. doi:10.1124/dmd.105.004390. ABBREVIATIONS: CL bile , biliary clearance (ml/min/kg body weight); CL hep , hepatic clearance (ml/min/kg body weight); CL int , intrinsic clearance (ml/min); C m , concentration medium (M); C s , concentration sandwich (M); D m , diffusion coefficient in medium (cm 2 /min); D s , diffusion coefficient in sandwich (cm 2 /min); f a , fraction of cell activity; f m , free fraction medium; f h , free fraction hepatocytes; f n , fraction of cells; f s , free fraction sandwich; f u , free fraction in blood; f v , fraction of viable cells; K h , specific clearance (Ϫ/min); K l , specific intrinsic clearance of the liver (Ϫ/min; Ϫ/h); K m , Michaelis-Menten constant (M); K ow , partition coefficient octanol-water; K s , first-order metabolism (Ϫ/min); L m , medium layer thickness (cm); L s , sandwich layer thickness (cm); PBPK, physiologically based pharmacokinetics; P cm , collagen-medium partition coefficient; P hm , hepatoyctemedium partition coefficient; P sm , sandwich-medium partition coefficient; P, parameter value; Q h , hepatic blood flow (l/h); s, sensitivity; SRW, standard rat body weight (250 g); V c , volume of collagen (ml); V h , volume of hepatocytes (ml); V m , volume of medium (ml); V max , maximum rate of metabolism (M/min); V s , volume sandwich (ml); DMEM, Dulbecco's modified Eagle's medium; FCS, fetal calf serum; HPLC, high-performance liquid chromatography

Randomised controlled trial of adjunctive inspiratory muscle training for patients with COPD.

BACKGROUND: This study aimed to investigate whether adjunctive inspiratory muscle training (IMT) can enhance the well-established benefits of pulmonary rehabilitation (PR) in patients with COPD. METHODS: 219 patients with COPD (FEV1: 42%±16% predicted) with inspiratory muscle weakness (PImax: 51±15 cm H2O) were randomised into an intervention group (IMT+PR; n=110) or a control group (Sham-IMT+PR; n=109) in this double-blind, multicentre randomised controlled trial between February 2012 and October 2016 (ClinicalTrials.gov NCT01397396). Improvement in 6 min walking distance (6MWD) was a priori defined as the primary outcome. Prespecified secondary outcomes included respiratory muscle function and endurance cycling time. FINDINGS: No significant differences between the intervention group (n=89) and the control group (n=85) in improvements in 6MWD were observed (0.3 m, 95% CI -13 to 14, p=0.967). Patients who completed assessments in the intervention group achieved larger gains in inspiratory muscle strength (effect size: 1.07, p<0.001) and endurance (effect size: 0.79, p<0.001) than patients in the control group. 75 s additional improvement in endurance cycling time (95% CI 1 to 149, p=0.048) and significant reductions in Borg dyspnoea score at isotime during the cycling test (95% CI -1.5 to -0.01, p=0.049) were observed in the intervention group. INTERPRETATION: Improvements in respiratory muscle function after adjunctive IMT did not translate into additional improvements in 6MWD (primary outcome). Additional gains in endurance time and reductions in symptoms of dyspnoea were observed during an endurance cycling test (secondary outcome) TRIAL REGISTRATION NUMBER: NCT01397396; Results

Baseline clinical characteristics of predicted structural and pain progressors in the IMI-APPROACH knee OA cohort

[Abstract] Objectives: To describe the relations between baseline clinical characteristics of the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) participants and their predicted probabilities for knee osteoarthritis (OA) structural (S) progression and/or pain (P) progression. Methods: Baseline clinical characteristics of the IMI-APPROACH participants were used for this study. Radiographs were evaluated according to Kellgren and Lawrence (K&L grade) and Knee Image Digital Analysis. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Numeric Rating Scale (NRS) were used to evaluate pain. Predicted progression scores for each individual were determined using machine learning models. Pearson correlation coefficients were used to evaluate correlations between scores for predicted progression and baseline characteristics. T-tests and χ2 tests were used to evaluate differences between participants with high versus low progression scores. Results: Participants with high S progressions score were found to have statistically significantly less structural damage compared with participants with low S progression scores (minimum Joint Space Width, minJSW 3.56 mm vs 1.63 mm; p<0.001, K&L grade; p=0.028). Participants with high P progression scores had statistically significantly more pain compared with participants with low P progression scores (KOOS pain 51.71 vs 82.11; p<0.001, NRS pain 6.7 vs 2.4; p<0.001). Conclusions: The baseline minJSW of the IMI-APPROACH participants contradicts the idea that the (predicted) course of knee OA follows a pattern of inertia, where patients who have progressed previously are more likely to display further progression. In contrast, for pain progressors the pattern of inertia seems valid, since participants with high P score already have more pain at baseline compared with participants with a low P score

Direct effects of doxorubicin on skeletal muscle contribute to fatigue

Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation followed in time by contraction impediment, which could be explained by DOX-induced changes in Ca2+ responses of myotubes in vitro. The Ca2+ responses in skeletal muscle, however, could not be explained by oxidative stress

Neuropathic Pain in the IMI-APPROACH Knee Osteoarthritis Cohort: Prevalence and Phenotyping

The study is registered under clinicaltrials.gov nr: NCT03883568.[Abstract] Objectives: Osteoarthritis (OA) patients with a neuropathic pain (NP) component may represent a specific phenotype. This study compares joint damage, pain and functional disability between knee OA patients with a likely NP component, and those without a likely NP component. Methods: Baseline data from the Innovative Medicines Initiative Applied Public-Private Research enabling OsteoArthritis Clinical Headway knee OA cohort study were used. Patients with a painDETECT score ≥19 (with likely NP component, n=24) were matched on a 1:2 ratio to patients with a painDETECT score ≤12 (without likely NP component), and similar knee and general pain (Knee Injury and Osteoarthritis Outcome Score pain and Short Form 36 pain). Pain, physical function and radiographic joint damage of multiple joints were determined and compared between OA patients with and without a likely NP component. Results: OA patients with painDETECT scores ≥19 had statistically significant less radiographic joint damage (p≤0.04 for Knee Images Digital Analysis parameters and Kellgren and Lawrence grade), but an impaired physical function (p<0.003 for all tests) compared with patients with a painDETECT score ≤12. In addition, more severe pain was found in joints other than the index knee (p≤0.001 for hips and hands), while joint damage throughout the body was not different. Conclusions: OA patients with a likely NP component, as determined with the painDETECT questionnaire, may represent a specific OA phenotype, where local and overall joint damage is not the main cause of pain and disability. Patients with this NP component will likely not benefit from general pain medication and/or disease-modifying OA drug (DMOAD) therapy. Reserved inclusion of these patients in DMOAD trials is advised in the quest for successful OA treatments