Identification of diagnostic serum protein profiles of glioblastoma patients

Diagnosis of a glioblastoma (GBM) is triggered by the onset of symptoms and is based on cerebral imaging and histological examination. Serum-based biomarkers may support detection of GBM. Here, we explored serum protein concentrations of GBM patients and used data mining to explore profiles of biomarkers and determine whether these are associated with the clinical status of the patients. Gene and protein expression data for astrocytoma and GBM were used to identify secreted proteins differently expressed in tumors and in normal brain tissues. Tumor expression and serum concentrations of 14 candidate proteins were analyzed for 23 GBM patients and nine healthy subjects. Data-mining methods involving all 14 proteins were used as an initial evaluation step to find clinically informative profiles. Data mining identified a serum protein profile formed by BMP2, HSP70, and CXCL10 that enabled correct assignment to the GBM group with specificity and sensitivity of 89 and 96%, respectively (p < 0.0001, Fischer’s exact test). Survival for more than 15 months after tumor resection was associated with a profile formed by TSP1, HSP70, and IGFBP3, enabling correct assignment in all cases (p < 0.0001, Fischer’s exact test). No correlation was found with tumor size or age of the patient. This study shows that robust serum profiles for GBM may be identified by data mining on the basis of a relatively small study cohort. Profiles of more than one biomarker enable more specific assignment to the GBM and survival group than those based on single proteins, confirming earlier attempts to correlate single markers with cancer. These conceptual findings will be a basis for validation in a larger sample size

In Vivo Human Apolipoprotein E Isoform Fractional Turnover Rates in the CNS

Apolipoprotein E (ApoE) is the strongest genetic risk factor for Alzheimer’s disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4) each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer’s disease (AD). Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ) peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS), we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Musculoskeletal pain in overweight and obese children

This review seeks to provide a current overview of musculoskeletal pain in overweight and obese children. Databases searched were Academic Search Complete, CINAHL, Medline, Proquest Health and Medical Complete, Scopus, Google Scholar, SPORTDiscuss and Trove for studies published between 1 January 2000 and 30 December 2012. We used a broad definition of children within a 3- to 18-year age range. The search strategy included the following terms: obesity, morbid obesity, overweight, pain, musculoskeletal pain, child, adolescent, chronic pain, back pain, lower back pain, knee pain, hip pain, foot pain and pelvic pain. Two authors independently assessed each record, and any disagreement was resolved by the third author. Data were analysed using a narrative thematic approach owing to the heterogeneity of reported outcome measures. Ninety-seven records were initially identified using a variety of terms associated with children, obesity and musculoskeletal pain. Ten studies were included for thematic analysis when predetermined inclusion criteria were applied. Bone deformity and dysfunction, pain reporting and the impact of children being overweight or obese on physical activity, exercise and quality of life were the three themes identified from the literature. Chronic pain, obesity and a reduction in physical functioning and activity may contribute to a cycle of weight gain that affects a child’s quality of life. Future studies are required to examine the sequela of overweight and obese children experiencing chronic musculoskeletal pain