A Radical Approach to Ebola: Saving Humans and Other Animals

As the usual regulatory framework did not fit well during the last Ebola outbreak, innovative thinking still needed. In the absence of an outbreak, randomised controlled trials of clinical efficacy in humans cannot be done, while during an outbreak such trials will continue to face significant practical, philosophical, and ethical challenges. This article argues that researchers should also test the safety and effectiveness of novel vaccines in wild apes by employing a pluralistic approach to evidence. There are three reasons to test vaccines in wild populations of apes: i) protect apes; ii) reduce Ebola transmission from wild animals to humans; and iii) accelerate vaccine development and licensing for humans. Data obtained from studies of vaccines among wild apes and chimpanzees may even be considered sufficient for licensing new vaccines for humans. This strategy will serve to benefit both wild apes and humans

Absolute Lymphocyte Count (ALC) after Induction Treatment Predicts Survival of Pediatric Patients with Acute Lymphoblastic Leukemia

Absolute Lymphocyte Count (ALC) has been recently established as a prognostic factor of survival in pediatric Acute Lymphoblastic Leukemia (ALL). A retrospective analysis of 132 patients treated according the BFM - ALLIC 2002 protocol was performed in a single institution. A possible association between ALC values and Overall Survival (OS) or Event-Free Survival (EFS) was evaluated at multiple time points during induction chemotherapy. ALC higher than 350 cells/muL measured on the 33th day of induction was associated with better Overall- and Event-Free Survival in both Kaplan-Meier (OS 88.6% vs. 40%; p 10 years). With help of day 33 ALC values of 350 cells/muL cutoff it was possible to refine day 33 flow cytometry (FC) Minimal Residual Disease (MRD) results within the negative cohort: higher ALC values were significantly associated with better survival. ALC on day 33 (350 cells/muL) remained prognostic for OS and EFS in multivariate analysis after adjusting it for age, cytogenetics, immunophenotype and FC MRD of induction day 33. According to these findings ALC on day 33 of induction is a strong predictor of survival in pediatric ALL

Identification of Hydroxysteroid (17β) dehydrogenase type 12 (HSD17B12) as a CD8+ T-cell-defined human tumor antigen of human carcinomas

Hydroxysteroid (17β) dehydrogenase type 12 (HSD17B12) is a multifunctional isoenzyme functional in the conversion of estrone to estradiol (E2), and elongation of long-chain fatty acids, in particular the conversion of palmitic to archadonic (AA) acid, the precursor of sterols and the inflammatory mediator, prostaglandin E(2). Its overexpression together with that of COX-2 in breast carcinoma is associated with a poor prognosis. We have identified the HSD17B12(114-122) peptide (IYDKIKTGL) as a naturally presented HLA-A*0201 (HLA-A2)-restricted CD8(+) T-cell-defined epitope. The HSD17B12(114-122) peptide, however, is poorly immunogenic in its in vitro ability to induce peptide-specific CD8(+) T cells. Acting as an optimized peptide , a peptide (TYDKIKTGL), which is identical to the HSD17B12(114-122) peptide except for threonine at residue 1, was required for inducing in vitro the expansion of CD8(+) T-cell effectors cross-reactive against the HSD17B12(114-122) peptide. In IFN-γ ELISPOT assays, these effector cells recognize HSD17B12(114-122) peptide-pulsed target cells, as well as HLA-A2(+) squamous cell carcinoma of the head and neck (SCCHN) and breast carcinoma cell lines overexpressing HSD17B12 and naturally presenting the epitope. Whereas growth inhibition of a breast carcinoma cell line induced by HSD17B12 knockdown was only reversed by AA, in a similar manner, the growth inhibition of the SCCHN PCI-13 cell line by HSD17B12 knockdown was reversed by E2 and AA. Our findings provide the basis for future studies aimed at developing cancer vaccines for targeting HSD17B12, which apparently can be functional in critical metabolic pathways involved in inflammation and cancer

Validation of the German version of the short form of the dysfunctional beliefs and attitudes about sleep scale (DBAS-16)

Research shows that dysfunctional sleep-related cognitions play an important role in the development, maintenance and exacerbation of insomnia. This study examines the factorial validity, psychometric properties and both concurrent and predictive validity of the German version of the 16-item DBAS (dysfunctional beliefs and attitudes about sleep) scale. Data was collected in 864 vocational students from the German-speaking part of Switzerland (43% females, M age = 17.9 years). Data collection took place twice within a 10-month interval. The students completed a German translation of the DBAS-16, the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), and provided information about their psychological functioning. Descriptive statistics, factorial validity, internal consistency, gender differences, concurrent, and predictive validity were examined. Confirmatory factor analysis supported the 4-factor structure of the DBAS-16. All factors (consequences, worry/helplessness, expectations, medication) were positively correlated and had acceptable psychometric properties. Females reported higher scores across all DBAS measures. Weak-to-moderate correlations were found between dysfunctional sleep-related beliefs, insomnia and poor sleep quality. Dysfunctional sleep-related beliefs were also associated with decreased psychological functioning, and consistently predicted insomnia and poor psychological functioning at follow-up, even after controlling for socio-demographic background and baseline levels. The present study provides support for the validity and psychometric properties of the German version of the DBAS-16. Most importantly, it corroborates the relevance of cognitive-emotional factors in the onset and maintenance of insomnia and psychological symptoms among young people