Increased CXCL10 (IP-10) is associated with advanced myeloproliferative neoplasms and its loss dampens erythrocytosis in mouse models.

Key studies in pre-leukemic disorders have linked increases in pro-inflammatory cytokines with accelerated phases of the disease, but the precise role of the cellular microenvironment in disease initiation and evolution remains poorly understood. In myeloproliferative neoplasms (MPNs), higher levels of specific cytokines have been previously correlated with increased disease severity (tumor necrosis factor-alpha [TNF-α], interferon gamma-induced protein-10 [IP-10 or CXCL10]) and decreased survival (interleukin 8 [IL-8]). Whereas TNF-α and IL-8 have been studied by numerous groups, there is a relative paucity of studies on IP-10 (CXCL10). Here we explore the relationship of IP-10 levels with detailed genomic and clinical data and undertake a complementary cytokine screen alongside functional assays in a wide range of MPN mouse models. Similar to patients, levels of IP-10 were increased in mice with more severe disease phenotypes (e.g., JAK2V617F/V617F TET2-/- double-mutant mice) compared with those with less severe phenotypes (e.g., CALRdel52 or JAK2+/V617F mice) and wild-type (WT) littermate controls. Although exposure to IP-10 did not directly alter proliferation or survival in single hematopoietic stem cells (HSCs) in vitro, IP-10-/- mice transplanted with disease-initiating HSCs developed an MPN phenotype more slowly, suggesting that the effect of IP-10 loss was noncell-autonomous. To explore the broader effects of IP-10 loss, we crossed IP-10-/- mice into a series of MPN mouse models and showed that its loss reduces the erythrocytosis observed in mice with the most severe phenotype. Together, these data point to a potential role for blocking IP-10 activity in the management of MPNs.

Longitudinal Cytokine Profiling Identifies GRO-α and EGF as Potential Biomarkers of Disease Progression in Essential Thrombocythemia.

Myeloproliferative neoplasms (MPNs) are characterized by deregulation of mature blood cell production and increased risk of myelofibrosis (MF) and leukemic transformation. Numerous driver mutations have been identified but substantial disease heterogeneity remains unexplained, implying the involvement of additional as yet unidentified factors. The inflammatory microenvironment has recently attracted attention as a crucial factor in MPN biology, in particular whether inflammatory cytokines and chemokines contribute to disease establishment or progression. Here we present a large-scale study of serum cytokine profiles in more than 400 MPN patients and identify an essential thrombocythemia (ET)-specific inflammatory cytokine signature consisting of Eotaxin, GRO-α, and EGF. Levels of 2 of these markers (GRO-α and EGF) in ET patients were associated with disease transformation in initial sample collection (GRO-α) or longitudinal sampling (EGF). In ET patients with extensive genomic profiling data (n = 183) cytokine levels added significant prognostic value for predicting transformation from ET to MF. Furthermore, CD56+CD14+ pro-inflammatory monocytes were identified as a novel source of increased GRO-α levels. These data implicate the immune cell microenvironment as a significant player in ET disease evolution and illustrate the utility of cytokines as potential biomarkers for reaching beyond genomic classification for disease stratification and monitoring.

Environmental and financial impact of a hospital recycling program.

Recycling decreases greenhouse gases (GHGs) emitted from waste disposal. A recent study determined the environmental and financial impact of recycling at a 148-bed acute care hospital in Cincinnati, Ohio. The hospital added single-stream recycling to its nonhazardous waste disposal practices in September 2008. The study measured the amount of nonhazardous waste generated and disposal costs from September 2008 to March 2009 for comparison with the same 6-month period in 2007-2008, calculating the environmental benefit using the Environmental Protection Agency's Waste Reduction Model (WARM). This study revealed that recycling benefits the environment and saves money. Recycling reduced GHG emissions by 34 metric ton carbon equivalents (MTCEs) and saved 632 million BTUs of energy. Pearson correlation for waste generation (r = 0.99, P = .002) demonstrates that the amount of waste generated between the control and intervention periods were very similar. Pearson correlation for facility operations as measured by admissions, outpatient visits, emergency room visits, and number of employees (r = 0.99, P < .007) also showed the 2 time periods to be very similar. The hospital's cost to dispose of nonhazardous waste decreased more than $4,670 after single-stream recycling.

Health insurance in the United States.

About two-thirds of Americans under the age of 65 have health insurance coverage. This leaves 43 million without. Sixteen million people with insurance are underinsured. Lack of insurance and inadequate insurance have serious consequences for individuals, families, and the country. This article provides facts about the current system of health insurance in the United States and government reform efforts.

Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons.

This paper describes the evaluation of the auto-catalytic anti-oxidant behavior and biocompatibility of cerium oxide nanoparticles for applications in spinal cord repair and other diseases of the central nervous system. The application of a single dose of nano-ceria at a nano-molar concentration is biocompatible, regenerative and provides a significant neuroprotective effect on adult rat spinal cord neurons. Retention of neuronal function is demonstrated from electrophysiological recordings and the possibility of its application to prevent ischemic insult is suggested from an oxidative injury assay. A mechanism is proposed to explain the auto-catalytic properties of these nanoparticles.

A defined system to allow skeletal muscle differentiation and subsequent integration with silicon microstructures.

This work documents the development of an in vitro cell culture model consisting of a novel serum-free medium and a non-biological growth substrate, N-1[3 (trimethoxysilyl) propyl] diethylenetriamine (DETA), to enable functional myotube integration with cantilevers fabricated using MEMS technology. This newly developed, defined in vitro model was used to study the differentiation of fetal rat skeletal muscle and it promoted the formation of myotubes from the dissociated rat fetal muscle cells. The myotubes were characterized by morphological analysis, immunocytochemistry and electrophysiology. Further, it was demonstrated that when the dissociated muscle cells were plated on fabricated microcantilevers, the muscle cells aligned along the major axis of the cantilever and formed robust myotubes. This novel system could not only find applications in skeletal muscle differentiation and biocompatibility studies but also in bioartificial muscle engineering, hybrid actuation system development, biorobotics and for a better understanding of myopathies and neuromuscular disorders.