Human Embryonic and Rat Adult Stem Cells with Primitive Endoderm-Like Phenotype Can Be Fated to Definitive Endoderm, and Finally Hepatocyte-Like Cells

Stem cell-derived hepatocytes may be an alternative cell source to treat liver diseases or to be used for pharmacological purposes. We developed a protocol that mimics mammalian liver development, to differentiate cells with pluripotent characteristics to hepatocyte-like cells. The protocol supports the stepwise differentiation of human embryonic stem cells (ESC) to cells with characteristics of primitive streak (PS)/mesendoderm (ME)/definitive endoderm (DE), hepatoblasts, and finally cells with phenotypic and functional characteristics of hepatocytes. Remarkably, the same protocol can also differentiate rat multipotent adult progenitor cells (rMAPCs) to hepatocyte-like cells, even though rMAPC are isolated clonally from cultured rat bone marrow (BM) and have characteristics of primitive endoderm cells. A fraction of rMAPCs can be fated to cells expressing genes consistent with a PS/ME/DE phenotype, preceding the acquisition of phenotypic and functional characteristics of hepatocytes. Although the hepatocyte-like progeny derived from both cell types is mixed, between 10–20% of cells are developmentally consistent with late fetal hepatocytes that have attained synthetic, storage and detoxifying functions near those of adult hepatocytes. This differentiation protocol will be useful for generating hepatocyte-like cells from rodent and human stem cells, and to gain insight into the early stages of liver development

Expert consensus document:Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted

Measuring moisture absorption in structural adhesive joints with fibre Bragg grating sensors

The increased joint efficiency, distribution of loads and decrease in stress concentrations have led to the increased use of adhesives for structural bonding. However, there are a limited number of techniques for verifying and monitoring the integrity and durability of adhesive bonds. This article studies the potential of estimating the curing and ageing of adhesive bulk samples with embedded fibre Bragg grating sensors through measuring the strain associated with hygroscopic expansion. This is achieved by relating the output of a fibre Bragg grating sensor to the deformation of the structure in which it is embedded. This work considers the possibility of mapping the changing structural resistance to mechanical loading (stiffness) of adhesive bonds as a function of time, under the influence of temperature and moisture as environmental factors. The goal is to map the influence of these environmental factors separately on the one hand, and their combined effect on adhesive bonds, on the other hand. This study subjects several bulk specimens to various environmental ageing loads. The swelling, associated to moisture absorption and that results in mechanical strain, is measured with fibre Bragg grating sensors. The moisture absorption behaviour at different temperatures and environmental relative humidity conditions determined in this way is verified using classical test methods (e.g. differential scanning calorimetry, gravimetric) on multiple fibreless specimens.status: publishe

Questionnaires are better than laboratory tests to screen for current alcohol abuse or dependence in a male inpatient population

OBJECTIVE: To assess the diagnostic performance of the CAGE and AUDIT (Alcohol Use Disorder Identification Test) and its derivatives, and laboratory tests for screening alcohol abuse or dependence in a male medical hospital population. DESIGN: A diagnostic cross-sectional prevalence study. SETTING: Three general hospitals and one university hospital. PATIENTS: All male patients older than 18 years admitted to the hospitals, during a period of 6 weeks, were consecutively included in the study (N = 233). MEASUREMENTS: Calculation of diagnostic measurements with 95% CI and ROC curves for different scores of CAGE, AUDIT and derivatives, laboratory tests and % Carbohydrate Deficient Transferrin (CDT), using DSM-III-R as the reference standard, derived from the CIDI. RESULTS: A current diagnosis of alcohol abuse or dependence was found in 29 medical male inpatients, representing 12.4% (95% CI: 8.6-17.5). Ten of these (4.2%) fulfilled criteria of alcohol abuse and 19 (8.2%) the criteria of alcohol dependence. Laboratory tests are useless as screening tools with sensitivities between 10% (%CDT) and 52% (GammaGT). Only the Fiveshot questionnaire seems to yield reasonable diagnostic parameters at the recommended cutpoint of > or = 2.5 with a sensitivity of 79.3% and a specificity of 87.7%. CONCLUSIONS: With a prevalence of 12.4%, our results are similar with other published studies for alcohol abuse and dependence according DSM criteria. The AUDIT as well as the Fiveshot seems to have the best diagnostic properties in this male medical inpatient population, and regarding to brief interventions, these questionnaires can be used as screening instruments as well as opportunities to talk about alcohol problems with admitted patients.status: publishe

Is there a difference between CAGE interviews and written CAGE questionnaires?

BACKGROUND: The CAGE questionnaire is a frequently studied and used instrument for screening of alcohol problems. It was developed and tested as a written questionnaire, but, clinically, it is often used as an oral interview. No comparisons have been made between the results of a written and an oral CAGE. This study attempted to (1) compare the results of a written CAGE questionnaire and a CAGE interview, and (2) compare the efficiency of using a simple open-ended question about drinking habits before asking the CAGE and asking the CAGE without an introduction. METHODS: All patients who attended a general internal medicine, cardiology, or hepatology clinic were classified according to the week of the consultation, as follows: group I (week 1), patients completed a written CAGE and were subsequently interviewed during a normal consultation by a physician, who also asked the CAGE questions; group II (week 2), a physician first interviewed the patients, including the CAGE, and subsequently patients completed a written CAGE; and group III (week 3), patients completed a CAGE interview after an open-ended introduction ("What do you drink during the day?"). Kappa values were used to compare the answers of the written and oral CAGE interviews (groups II and I). Nonparametric ANOVA was used to compare the results of group III and the oral interview of group II. RESULTS: Mean age was comparable between the groups, gender ratio was comparable between groups I and III, but there were fewer males in group II. Comparison of all written CAGEs with the oral CAGEs in the same patients resulted in an accuracy of 0.91 and a kappa value of 0.75 (95% CI, 0.66-0.84). No significant difference could be found between the results of the oral CAGE with or without an open-ended introduction (p = 0.46). CONCLUSIONS: We found no difference between the oral and the written versions of the CAGE. This is important because most research results originate from written questionnaires. Our results do not support the finding that a different approach to the CAGE questions results in an increasing number of patients in which alcohol problems were detected.status: publishe

Screening properties of questionnaires and laboratory tests for the detection of alcohol abuse or dependence in a general practice population

BACKGROUND: Early identification of alcohol abuse or dependence is important in general practice because many diseases are influenced by alcohol. General practitioners, however, fail to recognise most patients with alcohol problems. AIM: To assess the diagnostic performance of the CAGE and AUDIT questionnaires, their derivatives, and laboratory tests in screening for alcohol abuse or dependence in a primary care population (male and female patients), attending their general practitioner (GP). DESIGN OF STUDY: A diagnostic cross-sectional study. SETTING: A random sample of patients who were over 18 years of age (n = 1992) attending 69 general practices situated in the same region in Belgium. METHOD: Alcohol questionnaires (CIDI 1.1, section I, CAGE, AUDIT, AUDIT-C, Five-Shot, and AUDIT Piccinelli) were completed, demographic information was recorded, and patients underwent conventional blood tests, including mean corpuscular volume, liver function tests, the gamma-glutamyl transferase test, and carbohydrate-deficient transferrin (CDT, estimated using %CDT). Calculations of sensitivity, specificity, positive predictive value, negative predictive value, odds ratios with their 95% CIs, and receiver operating characteristic (ROC) curves for different scores of the questionnaires and laboratory tests, using DSM-III-R as the reference standard. RESULTS: The past-year prevalence of alcohol abuse or dependence in this population was 8.9% (178/1992) of which there were 132 male and 45 female patients attending a general practice. The GPs identified 33.5% of patients with alcohol abuse or dependence. Among male patients, all questionnaires had reasonable sensitivities between 68% and 93% and hence at lower cut-points than recommended. Only the sensitivity of the CAGE, even at its lowest cut-point of > or = 1 was lower (62%). In female patients the sensitivities were lower; however, odds ratios were higher for different questionnaires. The receiver operating characteristic (ROC) curves did not differ between the questionnaires. The laboratory tests had low diagnostic accuracy with areas under the ROC curves (AUCs) between 0.60 and 0.67 for female patients and 0.57 and 0.65 for male patients. CONCLUSIONS: This is one of the largest known studies on alcohol abuse or dependence among family care practices. We confirm earlier results that the AUDIT questionnaire seems equally appropriate for males and females; however, screening properties among male patients are higher. Nevertheless, the Five-Shot questionnaire is shorter and easier to use in a general practice setting and has nearly the same diagnostic properties in male and female general practice patient populations. We confirm that conventional laboratory tests are of no use for detecting alcohol abuse or dependence in a primary care setting. Also, the %CDT cannot been used as a screening instrument in this general practice population.status: publishe