The proteomic response in glioblastoma in young patients.

Increasing age is an important prognostic variable in glioblastoma (GBM). We have defined the proteomic response in GBM samples from 7 young patients (mean age 36 years) compared to peritumoural-control samples from 10 young patients (mean age 32 years). 2-Dimensional-gel-electrophoresis, image analysis, and protein identification (LC/MS) were performed. 68 proteins were significantly altered in young GBM samples with 29 proteins upregulated and 39 proteins downregulated. Over 50 proteins are described as altered in GBM for the first time. In a parallel analysis in old GBM (mean age 67 years), an excellent correlation could be demonstrated between the proteomic profile in young GBM and that in old GBM patients (r(2) = 0.95) with only 5 proteins altered significantly (p < 0.01). The proteomic response in young GBM patients highlighted alterations in protein-protein interactions in the immunoproteosome, NFkB signalling, and mitochondrial function and the same systems participated in the responses in old GBM patients.

Interactions among mitochondrial proteins altered in glioblastoma.

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥ 2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein-protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology.

Changes in health-related quality of life (HRQoL) after discharge from intensive care unit: a protocol for a systematic review.

INTRODUCTION: Treatment on an intensive care unit (ICU) imposes a high treatment burden on patients, as well as an economic burden for the healthcare provider. Many studies have recorded health-related quality of life (HRQoL) in patients after treatment on an ICU. We propose a systematic review of these studies. METHODS: We will search the National Library of Medicine's PubMed electronic database (PubMed), the Cochrane database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and Open Grey to identify papers reporting quality of life after discharge from ICU. We will include papers including validated quality of life measures. We will examine three categories: populations of patients treated on general ICUs, patients with severe infections and patients with respiratory dysfunction. We will extract HRQoL data. We will assess papers for risk of bias using the QUADAS-2 tool. The strength of our conclusions will depend on the quality and number of papers showing uniform results. ETHICS AND DISSEMINATION: This review will use published literature and contains no primary data; so we do not need ethical approval. We will submit the outcome of the systematic review to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015024700.