Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival.</p> <p>Methods</p> <p>A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers.</p> <p>Results</p> <p>A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively) or with other cancers (10, 19, and 15 genes, respectively) and the rest (16, 4, and 10 genes, respectively) are novel associations. <it>Pik3r1</it>, <it>E2f3, Akr1c3</it>, <it>Csf1</it>, <it>Jag2</it>, <it>Plcg1</it>, <it>Rpl37a</it>, <it>Sod2</it>, <it>Topors</it>, <it>Hras</it>, <it>Mdm2, Camk2g</it>, <it>Fstl1</it>, <it>Il13ra1</it>, <it>Mtap </it>and <it>Tp53 </it>were associated with multiple survival events.</p> <p>Most genes (from 90 to 96%) were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for <it>Syne1</it>, <it>Pdcd4</it>, <it>Ighg1</it>, <it>Tgfa</it>, <it>Pla2g7</it>, and <it>Paics</it>. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. <it>C2</it>, <it>Egfr</it>, <it>Prkcb</it>, <it>Igf2bp3</it>, and <it>Gdf10 </it>had gender-dependent associations; <it>Sox10</it>, <it>Rps20</it>, <it>Rab31</it>, and <it>Vav3 </it>had race-dependent associations; <it>Chi3l1</it>, <it>Prkcb</it>, <it>Polr2d</it>, and <it>Apool </it>had therapy-dependent associations. Biological processes associated glioblastoma survival included morphogenesis, cell cycle, aging, response to stimuli, and programmed cell death.</p> <p>Conclusions</p> <p>Known biomarkers of glioblastoma survival were confirmed, and new general and clinical-dependent gene profiles were uncovered. The comparison of biomarkers across glioblastoma phases and functional analyses offered insights into the role of genes. These findings support the development of more accurate and personalized prognostic tools and gene-based therapies that improve the survival and quality of life of individuals afflicted by glioblastoma multiforme.</p

Amputations in Diabetic Patients: A Plea for Footsparing Surgery

The authors observed a rather high rate of primary major amputation (above-knee or below-knee) performed for diabetic foot problems as well as an important revision rate for minor amputations (forefoot or toe) in diabetics. They reviewed their experience in order to compare it with more recent data from the literature, pleading for foot-sparing surgery. From 1993 to 1998, 186 amputations were performed on 146 diabetic patients. The cause of foot ulcers was neuropathy in 43 of them (51 episodes of diabetic foot problems) while in the remaining 103 patients (135 episodes of diabetic foot problems), diabetic macroangiopathy (absent ankle pulses) was on cause. For neuropathic foot problems, amputations were almost minor, resulting in a limb salvage rate of 90%. Only five of these patients (12%) had primary major limb amputation versus 43 of the dysvascular patients (42%). The reasons for major amputation by first intention were extensive tissue loss, intractable infection or non-reconstructible occlusive vessel disease, as judged by the surgeon. A foot-sparing surgery was attempted in 92 dysvascular cases. In only 44 of them, a preliminary vascular repair was performed. Twenty eight percent of the primary toe amputations and 24% of the forefoot amputations required secondary revision to a more proximal level. Minor amputations in case of diabetic neuropathy were characterized by a more favourable outcome: only 14% of the toe and 9% of the forefoot amputations failed. During follow-up, only 63% of the major amputations regained an autonomic walking capability with their prosthesis. Wound healing problems in diabetic foot are mainly due to infection and poor tissue perfusion. An aggressive control of the infection and distal revascularization of calf- or foot arteries, whenever possible, could improve the results of diabetic foot surgery. The poor functional recovery after major amputation (only 63% autonomic gait with limb prosthesis) argues for foot-sparing surgery whenever possible

Continuous dissolved gas tracing of fracture‐matrix exchanges

International audienceTransport in fractured media plays an important role in a range of processes, from rock weathering and microbial processes to contaminant transport, and energy extraction and storage. Diffusive transfer between the fracture fluid and the rock matrix is often a key element in these applications. But the multiscale heterogeneity of fractures renders the field assessment of these processes extremely challenging. This study explores the use of dissolved gases as tracers of fracture‐matrix interactions, which can be measured continuously and highly accurately using mobile mass spectrometers. Since their diffusion coefficients vary significantly, multiple gases are used to probe different scales of fracture‐matrix exchanges. Tracer tests with helium, xenon and argon were performed in a fractured chalk aquifer and resulting tracer breakthrough curves are modelled. Results show that continuous dissolved gas tracing with multiple tracers provide key constrains on fracture matrix interactions and reveal unexpected scale effects in fracture‐matrix exchange rates