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Aim: Serum high mobility group box 1 protein (HMGB1) is a proinflammatory molecule that could potentially serve as a biomarker for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) due to its correlation with degree of liver fibrosis. The aim of the current study was to examine the cross-sectional and longitudinal relationships between serum HMGB1 levels and liver histology in adults and children with NAFLD participating in two large randomized controlled trials., Methods: Serum HMGB1 levels were measured at various time points in adults and children with NAFLD, who participated in PIVENS and TONIC clinical trials respectively. PIVENS trial compared vitamin E or pioglitazone to placebo in adults whereas TONIC trial compared vitamin E or metformin to placebo in children. Participants had liver biopsies at baseline and the end of treatment (96 weeks), and liver histology was reviewed by a central committee of study pathologists., Results: In the cross-sectional analyses (n = 205 for PIVENS and 109 for TONIC), there was no significant relationship between serum HMGB1 levels and histological features such as steatosis, ballooning, inflammation, fibrosis, or presence of steatohepatitis in either adults or children. Serum HMGB1 levels did not change significantly during treatment either with placebo, vitamin E therapy (P = 0.81) or pioglitazone (P = 0.09) in the PIVENS trial. Similarly, serum HMGB1 levels did not change significantly during treatment either with placebo, metformin (P = 0.15) or vitamin E (P = 0.23) in the TONIC trial. In the longitudinal analyses (n = 105 for PIVENS and 109 for TONIC), changes in serum HMGB1 levels did not correlate with histologic improvement or resolution of NASH in either adults or children. There was no relationship between serum HMGB1 and ALT levels in either adults or children with NAFLD., Conclusion: Serum HMGB1 levels were not associated with histological severity or treatment response in either children or adults with NAFLD.

Background and Aim: Hepatocyte apoptosis or necrosis from accumulation of bile salts may play an important role in the disease progression of primary sclerosing cholangitis (PSC). The aim of the current study was to measure serum markers of hepatocyte apoptosis (cytokeratin-18 fragments--K18) and necrosis (high-mobility group protein B1--HMGB1) in adults with PSC and examine the relationship with disease severity., Methods: We measured serum levels of K18 and HMGB1 in well-phenotyped PSC (N = 37) and 39 control subjects (N = 39). Severity of PSC was assessed biochemically, histologically, and PSC Mayo risk score. Quantification of hepatocyte apoptosis was performed using TUNEL assay., Results: The mean age of the study cohort was 49.7 ± 13.3 years and comprised of 67% men and 93% Caucasian. Serum K18 levels were significantly higher in the PSC patients compared to control (217.4 ± 78.1 vs. 157.0 ± 58.2 U/L, p = 0.001). However, HMGB1 levels were not different between the two groups (5.38 ± 2.99 vs. 6.28 ± 2.85 ng/mL, p = 0.15). Within the PSC group, K18 levels significantly correlated with AST (r = 0.5, p = 0.002), alkaline phosphatase (r = 0.5, p = 0.001), total bilirubin (r = 0.61, p ≤ 0.001), and albumin (r = -0.4, p = 0.02). Serum K18 levels also correlated with the level of apoptosis present on the liver biopsy (r = 0.8, p ≤ 0.001) and Mayo risk score (r = 0.4, p = 0.015)., Conclusion: Serum K18 but not HMGB1 levels were increased in PSC and associated with severity of underlying liver disease and the degree of hepatocyte apoptosis.

Background & Aims: Cross-sectional studies have associated serum levels of the keratin 18 (K18) fragment with histologic features of liver in individuals with nonalcoholic fatty liver disease (NAFLD). We investigated the relationship between changes in serum levels of K18 and changes in liver histology in adults and children with NAFLD., Methods: We measured levels of K18 in stored serum samples collected at baseline and various time points from 231 adults with nonalcoholic steatohepatitis and 152 children with NAFLD who participated in 2 separate prospective randomized clinical trials. Liver biopsy specimens collected at baseline and week 96 were reviewed centrally., Results: There were greater decreases in serum levels of K18 in adults with histologic improvement at week 96 than in those without histologic improvement at week 16 (decrease, 193 ± 293 vs 139 ± 467 U/L; P < .001), week 48 (decrease, 232 ± 360 vs 113 ± 425 U/L; P < .001), or week 96 (decrease, 269 ± 368 vs 97 ± 400 U/L; P < .001). There were greater decreases in serum levels of K18 in children with histologic improvements than in those without histologic improvements at week 48 (decrease, 197 ± 467 vs 47 ± 350 U/L; P = .005) and week 96 (decrease, 206 ± 432 vs 2 ± 474 U/L; P < .001). However, reductions in serum levels of K18 were not better than reductions in levels of alanine aminotransferase in identifying adults with histologic improvement (area under the receiver operator characteristic [AUROC], 0.71; 95% confidence interval [CI], 0.63-0.80; vs AUROC, 0.68; 95% CI, 0.61-0.79; P = .34) or children (AUROC, 0.72; 95% CI, 0.63-0.81; vs AUROC, 0.79; 95% CI, 0.70-0.87; P = .42)., Conclusions: Decreases in serum levels of K18 are associated strongly with improved liver histologies in adults or children with NAFLD. However, reductions in K18 do not perform better than those in alanine aminotransferase level in identifying histologic changes in NAFLD., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

High and low self-handicappers (as measured by E. E. Jones & F. Rhodewalt's [1982] Self-Handicapping Scale) were asked to play a game of pinball (in a competitive or noncompetitive setting) after they had practices as much as they wanted on a related task (thus, not practicing could have served as a self-handicap). High self-handicappers who did not practice much became more involved in the game and subsequently reported enjoying the game more than high self-handicappers who practiced a lot. Furthermore, the effects on enjoyment were mediated by task involvement, suggesting that the protection afforded by self-handicapping affects intrinsic motivation by allowing the individual to become absorbed in the activity instead of focusing on performance concerns. Individuals who self-handicap may be providing themselves with the "breathing room" they need to become absorbed in an activity and to experience the activity as enjoyable.

The present study was an investigation of how Ss would respond when given 2 self-handicapping options, 1 behavioral (withdrawal of practice effort) and 1 self-reported (reporting high levels of stress). Ss anticipating a diagnostic test of intellectual ability were given different instructions regarding the effects of stress and practice on test performance. Ss were told that (a) stress only, (b) practice only, (c) both stress and practice, or (d) neither stress nor practice affected test scores. Ss were then given the opportunity to self-report a handicap on a stress inventory and to behaviorally self-handicap by failing to practice before the test. High self-handicapping men and women showed evidence of self-reported handicapping, but only high self-handicapping men behaviorally self-handicapped. However, when both self-handicaps were viable, both high self-handicapping men and women preferred the self-reported over the behavioral self-handicap.

In 47 out of 61 bce's, melanocytes were detectable with the aid of Dopa-reaction. In 24 of these cases, the percentage of tumour cells was less 5%, and in 23 it was more. The melanocytes preferred the periphery of the epithelial tumour formations. Only when the proportion of melanocytes exceeded 5% were they also to be found in the central parts of the tumours. Generally the melanocytes were more numerous in the upper parts of tumours, next to the epidermis. Our findings strengthen the opinion, that bce is a tumour of the primary hair germ.