Calyculin A from Discodermia Calyx Is a Dual ActionToxin that Blocks Calcium Influx and Inhibits Protein Ser/Thr Phosphatases

Calyculin A (Caly A) is cell permeable toxin widely used in cell biology research as an inhibitor of type 1 and type 2A protein Ser/Thr phosphatases of the PPP family. Here we tested effects of low concentrations of Caly A on proliferation of human cancer and non-cancer cell lines. We found that long-term 0.3 nM Caly A prevented G1 to S phase cell cycle progression in human Hs-68 fibroblasts and ARPE19 epithelial cells, but not human breast cancer MDA-MB-468, MDA-MB-231 and MCF7 cells. These conditions produced no change in cyclin D1 levels or in the phosphorylation of endogenous proteins. However, acute application of 0.3 nM Caly A blocked serum-induced increase in intracellular calcium levels in Hs-68 fibroblasts, but not in MDA-MB-468 breast cancer cells. We propose that subnanomolar Caly A prevents cell cycle progression because it blocks calcium uptake by fibroblasts. This probably involves non-selective cation channels and cancer cell proliferation was not affected because calcium enters these cells by other channels. Our results suggest that calyculin A has dual actions and acts as a channel blocker, in addition to its well-established effects as a phosphatase inhibitor.     

Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease

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Prevention of bacteremia caused by α-hemolytic streptococci by roxithromycin (RU-28 965) in granulocytopenic patients receiving ciprofloxacin

Summary We previously demonstrated that ciprofloxacin prevents infections caused by gram-negative bacilli in patients with granulocytopenia. However, in patients with intensive cytotoxic treatment leading to severe mucosal damage a high incidence of bacteremias caused by -hemolytic streptococci was seen. In the present study 45 consecutive patients undergoing intensive cytotoxic treatment received a short course of roxithromycin (10 days) in addition to ciprofloxacin for prevention of bacteremias caused by -hemolytic streptococci. The results of this study were compared with the results obtained in previous comparable patients receiving ciprofloxacin alone. During the days with addition of roxithromycin no infections caused by -hemolytic streptococci occurred, while in the control group of 80 patients 16 bacteremias (20%) were seen. Although roxithromycin was shown to antagonize bactericidal action of ciprofloxacin on gram-negative bacilliin vitro, in vivo study based on serum bactericidal titers and on results of surveillance cultures showed no antagonistic interactions.

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Roxithromycin (RU-28 965) zur Prävention der Bakteriämie durch alpha-hämolytische Streptokokken bei granulozytopenischen Patienten unter Ciprofloxacin-Prophylaxe

Zusammenfassung In früheren Studien konnte die präventive Wirksamkeit von Ciprofloxacin gegen Infektionen durch gramnegative Bakterien bei granulozytopenischen Patienten belegt werden. Jedoch traten bei Patienten, die mit intensiven Zytostatikaschemata behandelt wurden, häufig Bakteriämien durch alpha-hämolytische Streptokokken auf. In der vorliegenden Studie erhielten 45 Patienten, die nacheinander eingewiesen wurden und eine hochdosierte Zytostatikatherapie durchmachten, zehn Tage lang Roxithromycin als Zusatz zu einer Prophylaxe mit Ciprofloxacin, um das Auftreten septischer Infektionen durch alpha-hämolytische Streptokokken zu verhüten. Die Ergebnisse dieser Studie wurden denjenigen einer vorausgegangenen Studie mit vergleichbaren Patienten unter Prophylaxe mit Ciprofloxacin allein gegenübergestellt. Während in der Vergleichsgruppe bei 16 von 80 Patienten Bakteriämien durch alpha-hämolytische Streptokokken aufgetreten waren, kam es bei den Patienten, die Roxithromycin erhielten, zu keiner einzigen solchen Infektion, solange dieses Antibiotikum verabreicht wurde. Im Gegensatz zuIn vitro-Beobachtungen, die darauf schließen lassen, daß Roxithromycin die bakterizide Aktivität von Ciprofloxacin gegen gramnegative Bakterien antagonisiert, waren antagonistische Interaktionen in einerIn vivo-Studie anhand der Serumbakterizidietiter und Ergebnisse von Überwachungskulturen nicht festzustellen.

     

Cognitive dysfunction in children with brain tumors at diagnosis

Background

Survivors of brain tumors have a high risk for a wide range of cognitive problems. These dysfunctions are caused by the lesion itself and its surgical removal, as well as subsequent treatments (chemo‐ and/or radiation therapy). Multiple recent studies have indicated that children with brain tumors (BT) might already exhibit cognitive problems at diagnosis, i.e., before the start of any medical treatment. The aim of the present study was to investigate the baseline neuropsychological profile in children with BT compared to children with an oncological diagnosis not involving the central nervous system (CNS).

Methods

Twenty children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1–16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient's age. Furthermore, the child and his/her parent(s) completed self‐report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as surgery, chemotherapy, or irradiation. Groups were comparable with regard to age, gender, and socioeconomic status.

Results

Compared to the control group, patients with BTs performed significantly worse in tests of working memory, verbal memory, and attention (effect sizes between 0.28 and 0.47). In contrast, the areas of perceptual reasoning, processing speed, and verbal comprehension were preserved at the time of measurement.

Conclusion

Our results highlight the need for cognitive interventions early in the treatment process in order to minimize or prevent academic difficulties as patients return to school. Pediatr Blood Cancer 2015;62:1805–1812. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc.     

Diversity and education of the nursing workforce 2006–2016

Background

The Institute of Medicine (IOM) report, The Future of Nursing, included recommendations to increase nurse diversity, the percent of nurses obtaining a bachelor’s degree, and inter-professional education.