Putting the parts together: Combining in vitro methods to test for skin sensitizing potentials

Allergic contact dermatitis is a common skin disease and is elicited by repeated skin contact with an allergen. In the regulatory context, currently only data from animal experiments are acceptable to assess the skin sensitizing potential of substances. Animal welfare and EU Cosmetic Directive/Regulation call for the implementation of animal-free alternatives for safety assessments. The mechanisms that trigger skin sensitization are complex and various steps are involved. Therefore, a single in vitro method may not be able to accurately assess this endpoint. Non-animal methods are being developed and validated and can be used for testing strategies that ensure a reliable prediction of skin sensitization potentials. In this study, the predictivities of four in vitro assays, one in chemico and one in silico method addressing three different steps in the development of skin sensitization were assessed using 54 test substances of known sensitizing potential. The predictivity of single tests and combinations of these assays were compared. These data were used to develop an in vitro testing scheme and prediction model for the detection of skin sensitizers based on protein reactivity, activation of the Keap-1/Nrf2 signaling pathway and dendritic cell activation.     

Different neural melatonin-target tissues are critical for encoding and retrieving day length information in Siberian hamsters

Siberian hamsters exhibit several seasonal rhythms in physiology and behaviour, including reproduction, energy balance, body mass, and pelage colouration. Unambiguous long- and short day lengths stimulate and inhibit reproduction, respectively. Whether gonadal growth or regression occurs in an intermediate day length (e.g. 14 h L : 10 h D; 14L), depends on whether the antecedent day lengths were shorter (10L) or longer (16L). Variations in day length are encoded by the duration of nocturnal pineal melatonin secretion, which is decoded at several neural melatonin target tissues to control testicular structure and function. We assessed participation of three such structures in the acquisition and retrieval of day length information. Elimination of melatonin signalling to the nucleus reuniens (NRe), but not to the suprachiasmatic nucleus (SCN) or paraventricular thalamus (PVt), interfered with the acquisition of a long day reproductive response, whereas the obscuring of melatonin signals to the SCN and the NRe, but not to the PVt, interfered with the photoperiod history response. The SCN and NRe contribute in different ways to the melatonin-based system that mediates seasonal rhythms in male reproduction.     

BRCA1 und BRCA2: Mutationen und andere genetische Veränderungen – praktische Relevanz

Zusammenfassung. Bei 5–10 % aller an Mammacarcinom erkrankten Frauen ist die Erkrankung auf eine genetische Disposition zurückzuführen. Innerhalb der letzten 10 Jahre sind die wichtigsten disponierenden Gene für Mammacarcinom, BRCA1 und BRCA2, identifiziert worden. Beide Gene sind Tumorsuppressorgene, deren Funktion bislang noch nicht vollst?ndig aufgekl?rt ist. Die Gendiagnostik von BRCA1 und BRCA2 bildet die Grundlage, das Erkrankungsrisiko für Frauen aus Risikofamilien mit Mammacarcinom zu bestimmen und wird wichtige Informationen zur Pr?vention und Behandlung von erblichem Mammacarcinom geben.      

Duck hepatitis B virus infection of non-hepatocytes

One hundred and seventeen ducklings, 42 inoculated with duck hepatitis B virus (DHBV) 2 days after hatching and 55 connatally infected, were studied over a 6-month period in parallel with 20 ducklings without DHBV infection. Using immunohistochemical, in situ and blot hybridization analyses, the natural course of hepatic and extrahepatic infection was examined. DHBV infection started in the liver 2-4 days post-inoculation. There, DHBV was found not only in hepatocytes, but also in bile duct epithelial cells. Further, DHBV infection occurred in exocrine and endocrine pancreas (beginning 6-10 days and 20 days post-inoculation, respectively) and in germinal centers of the spleen (beginning 8 weeks post-inoculation). Occasionally viral DNA was also found in kidney glomeruli. Using strand-specific RNA probes, viral DNA in pancreas and spleen was clearly demonstrated to be replicating intermediates. Hepatic and extrahepatic infection with DHBV was not associated with histologic inflammation or pathologic changes in these tissues or the liver. These data indicate that DHBV can infect cells other than hepatocytes. The biological significance of non-hepatocyte infection for the life-cycle of the virus and its potential significance for viral persistence remain to be determined.     

Social cognitive or learning theory use to improve self-efficacy in musculoskeletal rehabilitation: A systematic review and meta-analysis

Objective: To review the rehabilitation research methodological quality and intervention effectiveness of studies that used social cognitive or learning theory principles to improve self-efficacy in patients with orthopedic or musculoskeletal conditions. Design: A systematic literature review and meta-analysis of peer reviewed studies published in English was performed using the OVID and SPORTDiscus databases. Initial search terms were “social cognitive theory” or “social learning theory” combined with “rehabilitation”. Results: From the 25 total studies that contributed to this review, 23 contributed patient outcome information and 20 contributed to effect size determination. Of 1947 total study participants, most (n = 1537, 78.9%) were women. Participants were primarily late middle-age (64.8 ± 17 years). Studies included participants with hip or knee osteoarthritis (OA) or who were post-hip or knee arthroplasty (11/25, 44%), post-femur or tibia fracture (6/25, 24%), adults in assisted living or inpatient rehabilitation facilities (2/25, 8%), independent community dwelling older adults (2/25, 8%), college-age recreational athletes post-sports injury (2/25, 8%), older women with osteoporosis risk (1/25, 4%) or middle-aged adults post-traumatic hand injury (1/25, 4%). For the 20 studies that contributed to effect size determination, a large overall mean effect size (Cohen’s d = 0.98, 95% CI 0.42–1.86) was observed. Conclusions: Studies that used social cognitive or learning theory principles to improve self-efficacy in patients with orthopedic or musculoskeletal conditions generally displayed moderate to large effect sizes supporting this intervention. Sound research methodological quality and low risk of intervention-related injury or other adverse events were also generally observed. Findings suggest that these interventions may also benefit individuals with conditions that have not progressed to end-stage salvage surgery such as younger, more athletically active individuals for knee OA prevention.