Inhibition of embryonic development by microcystin-LR in zebrafish, Danio rerio.

Microcystin-LR (MC-LR), a cyanobacterial toxin, is a potent inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A). PP1 and PP2A are critical regulators in embryonic development. However, the effects of MC-LR in embryonic development have been controversial. MC-LR has been demonstrated to be highly toxic in medaka, but not in zebrafish or rabbit embryos. The causes of difference may be due to membrane impermeability that impaired the delivery of MC-LR into cytoplasm of zebrafish and rabbit embryos. Therefore, we microinjected MC-LR directly into developing zebrafish embryos and investigated the effects of MC-LR on embryonic development. We demonstrated that MC-LR induced the lethality of zebrafish embryos in a dose- and time-dependent manner. MC-LR also induced the loss of blastomere coherence via the interference of beta-catenin and cadherins distributions. Furthermore, the MC-LR treated fry revealed various developmental defects. These results suggested that MC-LR might affect the phosphorylation equilibrium of signaling molecules, including beta-catenin and cadherins, required early in zebrafish embryonic development.     

The Relationship Between Quality of Life and Psychiatric Impairment for a Taiwanese Community Post-Earthquake

This purpose of this study was to investigate the relationship between quality of life and psychiatric impairment in a Taiwanese community located near the epicenter of the 1999 earthquake, as assessed four to six months after the natural catastrophe. Trained assistants interviewed the 4223 respondents using the disaster-related psychological screening test (DRPST), an instrument specifically designed and validated by senior psychiatrists for assessment of psychiatric impairment after natural catastrophe. Additionally, the 36-Item Short-Form Health Survey (SF-36) was used to evaluate quality of life. The collected results were analyzed using Windows SPSS 10.0 software. Psychiatric impairment rated moderate to severe was assessed for 1448 (34.3%) of the responding residents. The 4223 respondents were divided into 4 psychiatric-impairment groups based on DPRST score: healthy (n = 952); mild impairment (n = 1823); moderate impairment (n = 1126); and, severe impairment (n = 322). The four groups were compared for a number of salient factors, including gender, age, current marital status and psychiatric-impairment score, to determine impact on quality of life. Respondents assessed as psychiatrically impaired tended to be older, female, divorced/widowed, and less educated, and they were more likely to have experienced major familial financial loss as an immediate consequence of the earthquake. Further, the greater the severity of the psychiatric impairment, the lower the scores for quality of life, for both the physical and mental aspects of this important general indicator.     

Emotional intelligence and smoking risk factors in adolescents: interactions on smoking intentions.

PURPOSE: To examine interactions between emotional intelligence (EI) and smoking risk factors on smoking intentions in adolescents. METHODS: EI ios defined as the ability to: accurately perceive, appraise, and express emotion; access and/or generate feelings in facilitating thought; understand emotion and emotional knowledge; and regulate emotions. EI of 416 6th graders (53% girls) from middle schools in the Los Angeles area (mean age = 11.3 years; 32% Latino, 29% Asian/Pacific Islander, 13% white, 19% Multiethnic, 6% Other) was assessed with an abbreviated version of the Multifactor Emotional Intelligence Scale, Adolescent Version (MEIS). This was a competence-based measure assessing an individual's ability to perceive, understand, and manage emotion. Logistic regression models were fit to test interactions between EI and ever trying cigarettes, hostility, and perceived ability to refuse a cigarette from someone just met, on intentions to smoke in the next year. RESULTS: High EI adolescents were more likely to intend to smoke in the next year if they had previously experimented with smoking. Those with low EI were more likely to intend to smoke if their perceived ability to refuse a cigarette offer from a person they just met was low or hostility level was high. CONCLUSIONS: These preliminary results indicate that EI interacts with risk factors to reduce smoking intentions, and contributes evidence to a link between EI and smoking in adolescents.     

Correlation of minimal residual disease by assessing Wilms tumor gene expression and engraftment by variable number of tandem repeats in children with leukemia posthematopoietic stem cell transplantation.

An important measure to ensure successful follow-up in patients with allogeneic stem cell transplant is to evaluate for engraftment. Recent studies have shown that detecting minimal residual disease is important in order to predict early clinical relapse. We followed 88 leukemic patients with pre- and posttransplant Wilms tumor gene (WT1) levels to predict relapse and variable number of tandem repeats (VNTR) for engraftment. We have found that high pretransplant WT1 levels correlated significantly with relapse in all patient groups, but more significantly in the acute nonlymphoblastic leukemia (ANLL) patients. Posttransplant WT1 level correlated with VNTR status such that low WT1 is associated invariably with VNTR of 100% donor origin, while high WT1 is associated with VNTR of 20%. The association is significant in all patients, specifically in ANLL patients. In this preliminary study, we demonstrate that patients harboring detectable levels of WT1 prior to stem cell transplant have a higher chance of relapse, and posttransplant WT1 and VNTR status appeared to be dependent parameters predicting relapse when present in the posttransplant period. By combining 2 highly sensitive molecular techniques, we have found that this combined technique provided us with a promising alternative for overcoming the limitations imposed by each separate procedure. More studies are necessary before we can come to any significant conclusions.     

Erythropoietin and erythropoietin receptor expression in head and neck cancer: relationship to tumor hypoxia.

PURPOSE: Erythropoietin, an oxygen-regulated glycoprotein hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor [erythropoietin receptor (EPOR)]. The recombinant form of human erythropoietin is used to prevent or treat anemia in cancer patients. However, in a recent randomized, placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck, erythropoietin treatment was associated with poorer locoregional progression-free survival. The purpose of our study was to determine whether EPOR and its ligand erythropoietin are expressed in primary head and neck cancer. We also investigated the hypothesis that erythropoietin expression in malignant cells may be associated with the presence of tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness, and poor prognosis. EXPERIMENTAL DESIGN: Twenty-one patients received an i.v. infusion of the hypoxia marker pimonidazole hydrochloride before multiple tumor biopsies. Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for EPOR and erythropoietin expression and pimonidazole binding. RESULTS: EPOR expression was present in tumor cells in 97% of the biopsies. Coexpression of erythropoietin was observed in 90% of biopsies. Erythropoietin and pimonidazole adduct staining did not always colocalize within tumors, but there was a significant positive correlation between levels of microregional erythropoietin expression and pimonidazole binding. CONCLUSIONS: The coexpression of erythropoietin and EPOR in tumor cells suggests that erythropoietin may potentially function as an autocrine or paracrine factor in head and neck cancer. The expression of the hypoxia-inducible protein erythropoietin in tumor cells correlates with levels of tumor hypoxia.     

Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer.

PURPOSE: Mutations in epidermal growth factor receptor (EGFR) can be used to predict the tumor response of patients receiving gefitinib for non-small cell lung cancer (NSCLC). We investigated the association between mutations in EGFR tyrosine kinase domain and tumor response and survival in gefitinib-treated NSCLC patients. EXPERIMENTAL DESIGN: EGFR mutations in exons 18 to 21 were analyzed by DNA sequencing of paraffin-embedded tumor tissues from gefitinib-treated NSCLC patients. The results were correlated with clinical variables. RESULTS: EGFR mutations were found in 61.1% (33 of 54) of cases; response rate and disease control rate were 56.8% and 68.5%, respectively. There was no significant difference in mutation rates between adenocarcinoma (29 of 43) and nonadenocarcinoma (4 of 11; P = 0.085). However, all four nonadenocarcinomas with EGFR mutations had no response to gefitinib. Presence of EGFR mutations was the only independent predictor for disease control (P = 0.003) and tumor response (P = 0.017) in multivariate analysis; positive predictive values were 87.9% and 70.8% and negative predictive values were 61.9% and 69.2%, respectively. In comparison with patients whose tumor was negative for EGFR mutations, patients with EGFR mutations had better progression-free survival (median, 7.6 versus 1.7 months; P = 0.011) and overall survival (median, 14.7 versus 4.7 months; P = 0.046). CONCLUSIONS: Mutations in EGFR tyrosine kinase correlate with treatment response and survival in gefitinib-treated NSCLC patients and can be used as a predictive and prognostic factor. Thus, analysis of EGFR tyrosine kinase mutations in lung adenocarcinoma is of clinical significance, as it can permit the customization of treatment with EGFR tyrosine kinase inhibitors.     

A systematic review on the effectiveness of sex offender risk assessment tools in predicting sexual recidivism of adult male sex offenders

PurposeThis study aimed to systematically review the effectiveness of risk assessment tools in predicting sexual recidivism of adult male offenders.BackgroundSex offender risk assessment aids risk management within the criminal justice system. Some tools follow an actuarial approach and some adopt structured professional judgement. There has not been a systematic review evaluating and comparing the effectiveness of those tools and appraising the overall quality of the primary research.MethodsSix electronic databases and reference lists of relevant meta-analyses were searched. Three experts were contacted to obtain relevant studies. Inclusion criteria were applied to the identified references and the included studies were quality assessed, using pre-defined criteria, prior to data extraction and synthesis.ResultsElectronic search yielded 4949 hits. Of these, 1419 duplicates, 1 meta-analysis and 3382 irrelevant hits were excluded. 14 publications identified from previous meta-analyses were included. 2 non-English language duplications of publications were excluded. 89 publications that did not meet inclusion criteria and 15 inaccessible publications were excluded. 11 studies that did not meet minimum threshold criteria and 1 study that re-analysed an already included sample were then excluded, leaving 43 publications containing 43 studies.ConclusionsAll included tools demonstrated at least moderate predictive accuracy, with two reporting a large effect size (VRS-SO and SRA), although these two came under much less empirical scrutiny than the others and may have been the subject of developer bias in the research that is available. The VRS-SO was found to have the highest mean quality score, this again being limited by the number of studies and developer bias. The quality of the primary research is variable. More independent high quality research is needed, particularly on structured professional judgement incorporating dynamic risk factors.     

Serum creatinine to cystatin C ratio is associated with major adverse cardiovascular events in patients with obstructive coronary artery disease

Background & aimsSarcopenia is a clinical syndrome that features muscle atrophy and weakness, and has been associated with cardiovascular events and poor clinical outcomes. Recently, the sarcopenia index (SI) was developed as a simple screening tool based upon the serum creatinine to cystatin C (CysC) ratio. We investigated the association between SI and the prevalence of major adverse cardiovascular events (MACE) in patients with obstructive CAD.Methods & ResultsBetween January 2010 and December 2018, patients with angina pectoris and obstructive CAD requiring coronary artery intervention were enrolled. Serum levels of CysC and other biomarkers were assessed. Patients were divided into two groups according to the SI ([Cr/CysC] x 100). Demographic characteristics and clinical outcomes of the two groups were evaluated. A total of 427 patients (79.6% men, mean age 69.55 ± 12.04 years) were enrolled. Patients with SI < 120 (n = 214, 28%) were older, more likely to be of the female gender, and to have more hypertension and congestive heart failure (all p < 0.05). The prevalence of major adverse cardiovascular events (MACE) composed of myocardial infarction, stroke, and all-cause mortality was higher in patients with lower SI (p = 0.026). After adjusting for potential confounding factors, multivariate Cox regression (hazard ratio 2.08, p = 0.045) and Kaplan–Meier analyses (log-rank p = 0.0371) revealed that lower SI was significantly associated with a higher prevalence of MACE.ConclusionsSerum creatinine to cystatin C ratio (SI) may be a useful surrogate marker to predict the future prevalence of MACE in patients with obstructive CAD.