Perturbations in neuroinflammatory pathways are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors.

Paclitaxel is a common chemotherapy drug associated with the development of chronic paclitaxel-induced peripheral neuropathy (PIPN). PIPN is associated with neuroinflammatory mechanisms in pre-clinical studies. Here, we evaluated for differential gene expression (DGE) in peripheral blood between breast cancer survivors with and without PIPN and for neuroinflammatory (NI) related signaling pathways and whole-transcriptome profiles from other experiments. Pathway impact analysis identified 8 perturbed NI related pathways. Expression profile analysis found 15 experiments having similar whole-transcriptome profiles of DGE related to neuroinflammation and PIPN. These findings suggest that perturbations in pathways associated with neuroinflammation are found in cancer survivors with PIPN

Evaluation of an Occupational Health and Safety Management System Performance Measurement Tool-III: Measurement of Initiation Elements

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91920/1/Redinger4.pd

Loss of foundation species revisited: conceptual framework with lessons learned from eastern hemlock and whitebark pine

Ecologists and conservation biologists often prioritize the study of species that are declining, threatened, or endangered over species that are abundant and ecologically important, such as foundation species (FS ). Because entire ecosystems and their biodiversity depend on FS , we argue that they have high conservation priority. A citation analysis reveals that FS are studied, but often are characterized ambiguously. More effort is needed to identify FS before they, and the ecosystems they define, are at risk of decline or loss. We suggest a new conceptual framework that includes: informed identification of FS in ecosystems; documentation of ecosystem services provided by FS ; a long‐term monitoring strategy to detect threats to FS within specified ecosystems; and, if threats are identified, a comprehensive conservation and adaptive management strategy for FS . We use two widely distributed, rapidly declining North American foundation tree species (Tsuga canadensis [eastern hemlock] and Pinus albicaulis [whitebark pine]) to illustrate this framework. These species exemplify the importance of identifying FS early and conserving or restoring them when they are threatened

Iron deposition is independent of cellular inflammation in a cerebral model of multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Perivenular inflammation is a common early pathological feature in multiple sclerosis (MS). A recent hypothesis stated that CNS inflammation is induced by perivenular iron deposits that occur in response to altered blood flow in MS subjects. In order to evaluate this hypothesis, an animal model was developed, called cerebral experimental autoimmune encephalomyelitis (cEAE), which presents with CNS perivascular iron deposits. This model was used to investigate the relationship of iron deposition to inflammation.</p> <p>Methods</p> <p>In order to generate cEAE, mice were given an encephalitogen injection followed by a stereotactic intracerebral injection of TNF-α and IFN-γ. Control animals received encephalitogen followed by an intracerebral injection of saline, or no encephalitogen plus an intracerebral injection of saline or cytokines. Laser Doppler was used to measure cerebral blood flow. MRI and iron histochemistry were used to localize iron deposits. Additional histological procedures were used to localize inflammatory cell infiltrates, microgliosis and astrogliosis.</p> <p>Results</p> <p>Doppler analysis revealed that cEAE mice had a reduction in cerebral blood flow compared to controls. MRI revealed T2 hypointense areas in cEAE animals that spatially correlated with iron deposition around vessels and at some sites of inflammation as detected by iron histochemistry. Vessels with associated iron deposits were distributed across both hemispheres. Mice with cEAE had more iron-labeled vessels compared to controls, but these vessels were not commonly associated with inflammatory cell infiltrates. Some iron-laden vessels had associated microgliosis that was above the background microglial response, and iron deposits were observed within reactive microglia. Vessels with associated astrogliosis were more commonly observed without colocalization of iron deposits.</p> <p>Conclusion</p> <p>The findings indicate that iron deposition around vessels can occur independently of inflammation providing evidence against the hypothesis that iron deposits account for inflammatory cell infiltrates observed in MS.</p

P1‐567: Cognitive Impairment And Community Resource Needs For Older Mexican Americans: The Brain Attack Surveillance In Corpus Christi (Basic)‐Cognitive Project

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152518/1/alzjjalz2019061172.pd

Deferiprone modulates in vitro responses by peripheral blood T cells from control and relapsing remitting multiple sclerosis subjects

T cells are important mediators of autoimmune inflammation in relapsing remitting multiple sclerosis (RRMS). Previous studies found that deferiprone, an iron chelator, suppressed disease activity in a mouse model of multiple sclerosis, and inhibition of T cell proliferation was implicated as a putative mechanism. The objective of the present study was to examine the effects of deferiprone on suppressing in vitro responses of T cells from control and RRMS subjects. Peripheral blood T cells were co-stimulated with anti-CD3 + anti-CD28 and cultured with or without interleukin 2 (IL-2). Proliferating CD4+ T cells from control and RRMS subjects, cultured with or without IL-2, decreased in response to 75 μM deferiprone, although the extent of decreased proliferation of CD4+ T cells from RRMS subjects was less than for control subjects. Proliferating CD8+ T cells from control subjects, cultured with or without IL-2, also decreased in response to 75 μM deferiprone, and this decrease was seen in proliferating CD8+ T cells from RRMS cultured with IL-2. CD4+CD25+ and CD8+CD25+ cells from control subjects, cultured with or without IL-2, declined in 75 M deferiprone, but the decrease was smaller than for the CD4+ and CD8+ proliferative responses. CD4+CD25+ and CD8+CD25+ cells from RRMS subjects showed more variability than for control subjects, but CD4+CD25+ cultured with IL-2 and CD8+CD25+ cells cultured without IL-2 significantly declined in 75 μM deferiprone. CD4+FoxP3+ and CD4+CD25+FoxP3+ cells tended to remain constant or increase. In summary, deferiprone induced declines in proliferative responses at a dosage that is within peak serum pharmacological concentrations

Evidence Based Review: Risk of Cardiac Rhythm Problems During Spaceflight

Very little research has systematically evaluated the prevalence (or potential risk) of cardiac arrhythmias during space flight. There are several observational reports of non life-threatening but potentially concerning arrhythmias. At least two potential risk factors for arrhythmias have been reported either during or immediately after space flight: cardiac atrophy and a prolonged QTc interval. The potential severity of the mission impact of a serious arrhythmia requires that a systematic evaluation be conducted of the risk of arrhythmia due to space flight