Pegylated IFN-α sensitizes melanoma cells to chemotherapy and causes premature senescence in endothelial cells by IRF-1-mediated signaling

Pegylated interferon-α2b (pIFN-α) is an integral part of the drug regimen currently employed against melanoma. Interferon regulatory factor-1 (IRF-1) has an important role in the transcriptional regulation of the IFN response, cell cycle and apoptosis. We have studied pIFN-α-induced responses when combined with the chemotherapy agent, vinblastine (VBL), in tumor and endothelial cell lines and the connection to IRF-1 signaling. Levels of IRF-1/IRF-2 protein expression were found to be decreased in tumor versus normal tissues. pIFN-α induced IRF-1 signaling in human melanoma (M14) and endothelial (EA.hy926) cells and enhanced cell death when combined with VBL. Upon combined IFN-α and VBL treatment, p21 expression, poly (ADP-ribose) polymerase cleavage and activated Bak levels were increased in M14 cells. An increase in p21 and cyclin D1 expression occurred in EA.hy926 cells after 6 h of treatment with pIFN-α, which dissipated by 24 h. This biphasic response, characteristic of cellular senescence, was more pronounced upon combined treatment. Exposure of the EA.hy926 cells to pIFN-α was associated with an enlarged, multinucleated, β-galactosidase-positive senescent phenotype. The overall therapeutic mechanism of IFN-α combined with chemotherapy may be due to both direct tumor cell death via IRF-1 signaling and by premature senescence of endothelial cells and subsequent effects on angiogenesis in the tumor microenvironment

The lived experience of adults with myasthenia gravis: a phenomenological study

Myasthenia gravis (MG) is a disorder of the neuromuscular junction (NMJ) that causes fatigue and fluctuating muscle weakness. The physiology of this disease is well understood and there are numerous medically focused articles that outline historical data, randomized controlled trials of treatment options and unusual case studies. There is limited nursing literature about MG; most nurse-led research focuses on fatigue. No published research examines the life experiences of people with MG. The aim of this study was to examine and understand the lived experiences of adults with MG. An interpretive phenomenological approach has been used that applies the research methodology of van Manen (1990). Seven people living with MG were interviewed and their experiences of the disease recorded. Questions were broadly worded about various topics related to MG, that included diagnosis, symptoms, treatments and coping strategies, and were guided by individual experiences. Thematic analysis revealed that MG affects every aspect of a person’s ‘lifeworld’: their sense of time, body, space and their relationships with others. The findings of this study highlight three main themes embedded in the data that a person with MG experiences: living with uncertainty, living with weakness and living with change. These experiences have been interpreted and discussed to gain a deep understanding of the meaning of the disease. This study raises awareness of MG for nurses and other health professionals. It provides a unique view of the disease and explores the meaning of MG, from a perspective where a paucity of such literature exists

Conservation and ecology of African Raptors

Africa supports breeding populations of over 20% of all raptor species globally and over 20 regular Palearctic migratory raptors. Here, we discuss the importance of Africa in terms of the diversity of both resident and migrant species, the ecosystem services they provide, and the threats they face. We examine the state of knowledge of African raptors, including monitoring to determine trends, and describe ongoing research. African raptors provide important ecosystem services, by bringing in tourism revenues, functioning as bio-indicator species, and controlling the spread of pathogens and pest species. Many species are under pressure from growing human populations and associated habitat loss, persecution, and pollution. Most are declining, with some exceptions, some catastrophically so, such as vultures. Of 66 African species, 26% are currently on the IUCN Red List. For many species, there is a need for their conservation status to be re-evaluated, but rigorous monitoring for most of Africa is generally lacking. A systematic literature review showed considerable variation in the number of studies per species, 36% of 67 species having been relatively “well-studied” (12 or more studies), but 64% with less than 10 studies. There has been a general and consistent increase in the numbers of studies on African raptors, the majority from Southern Africa (n = 466, 62%). We found most studies focused on feeding ecology (n= 247) and distribution and abundance, with the least number of studies on behaviour and movement ecology. We list some ongoing studies and conclude that developing future leadership in research and conservation will be critical for successful raptor conservation in Africa