Assessment of home care aides' respiratory exposure to total volatile organic compounds and chlorine during simulated bathroom cleaning: An experimental design with conventional and "green" products.

Home care (HC) aide visits to clients' homes often involve cleaning and disinfecting (C&D) bathrooms. Some ingredients in C&D household products are associated with respiratory illness, including sodium hypochlorite (bleach) and quaternary ammonium compounds (quats). "Green" products may be safer for the environment, however there are limited quantitative evaluations of their respiratory risks. This study assessed airborne concentrations and time profiles of total volatile organic compounds (TVOC) and chlorine generated during typical bathroom cleaning performed by aides using conventional and green products. Aides performed cleaning tasks in a simulated residential bathroom constructed in an environmental air sampling laboratory. A balanced experimental design involved each aide coming to the lab for four visits during which she performed two 20-min cleaning sessions using one of three C&D products (bleach-based, 1-5% sodium hypochlorite by weight; quats-based, 0.1-1% by weight quaternary ammonium compounds; and "green," 0.05% by weight thymol, a component of botanical thyme oil) or distilled water as a control. TVOC and chlorine direct reading instruments were attached to aides with sample inlets located in the breathing zone. Ten-second averages of TVOC and chlorine gas concentrations and instantaneous peak concentrations were recorded for the sessions' duration. TVOC concentrations by methods of C&D application (spraying, streaming, wiping) also were evaluated. The study completed 169 air sampling sessions with 22 aides. The quats-based product generated more than twice the average TVOC concentrations (mean = 1,210 ppb) than the bleach-based (mean = 593 ppb) or green (mean = 498 ppb) products. Each product generated TVOC concentrations that rose rapidly within the first few minutes of application. Spraying produced the highest TVOC exposures, wiping the lowest. Thirteen aides (65%) experienced peak chlorine exposures above the OSHA PEL ceiling limit (1 ppm) when using the bleach-based product. HC aides may experience respiratory hazards from use of conventional or green C&D products formulated with bleach or other respiratory irritants and sprayed in small, poorly ventilated spaces typical of bathrooms. Spraying should be avoided.

Healthy Aging Requires a Healthy Home Care Workforce: the Occupational Safety and Health of Home Care Aides.

PURPOSE OF REVIEW: To identify important home care (HC) aide occupational safety and health (OSH) hazards and examine how addressing these can improve aide health and the delivery of HC services overall. Specifically, this review seeks to answer: Why is HC aide OSH important? What are the most significant OSH challenges? How can improving HC aide OSH also improve the safety and health of their clients? What implications do the findings have for future research? RECENT FINDINGS: HC is one of the fastest growing US industries. Aides comprise its largest workforce and are increasingly needed to care for the rapidly aging population. There is an aide shortage due in part to instabilities in HC work organization and to serious job-specific hazards, resulting in aides losing work time. Recent social, economic, and technological factors are rapidly changing the nature of HC work, creating OSH hazards similar to those found in nursing homes. At the same time, aides are experiencing social and economic inequities that increase their vulnerability to OSH hazards. These hazards are also a burden on employers who are challenged to recruit, retain, and train aides. OSH injuries and illness interrupt the continuity of care delivery to clients. Many OSH hazards also put HC clients and families at risk. A new framework and methodologies are needed to assess aide and client safety together in order to guide future HC research, policies, and practices. Government, industry, and labor commitment is needed to fund and coordinate a comprehensive, multidisciplinary research program.

Mesoscale blood cell sedimentation for processing millilitre sample volumes.

We demonstrate the efficient separation of blood cells from millilitre volumes of whole blood in minutes using a simple gravity sedimentation device. Blood cell and plasma separation is often the initial step in clinical diagnostics, and reliable separation techniques have remained a major obstacle for the success of point-of-care or remote diagnostics. Unlike plasma collection devices that rely solely on microchannels that restrict sample volume and throughput, we demonstrate the use of a hybrid micro/mesoscale sedimentation chamber to enable >99% capture of cells from millilitre blood samples in less than two minutes.

Interferon-beta is a key regulator of proinflammatory events in experimental autoimmune encephalomyelitis.

BACKGROUND: Interferon (IFN)-ß is an effective therapy for relapsing-remitting multiple sclerosis, yet its mechanism of action remains ill-defined. OBJECTIVES: Our objective was to characterize the role of IFN-ß in immune regulation in experimental autoimmune encephalomyelitis (EAE). METHODS: IFN-ß(+/+) and IFN-ß(-/-) mice were immunized with myelin oligodendrocyte glycoprotein peptide in the presence or absence of IFN-ß, to induce EAE. Disease pathogenesis was monitored in the context of incidence, time of onset, clinical score, and immune cell activation in the brains, spleens and lymph nodes of affected mice. RESULTS: Compared with IFN-ß(+/+) mice, IFN-ß(-/-) mice exhibited an earlier onset and a more rapid progression of EAE, increased numbers of CD11b(+) leukocytes infiltrating affected brains and an increased percentage of Th17 cells in the central nervous system and draining lymph nodes. IFN-ß treatment delayed disease onset and reduced disease severity. Ex vivo experiments revealed that the lack of IFN-ß results in enhanced generation of autoreactive T cells, a likely consequence of the absence of IFN-ß-regulated events in both the CD4(+) T cells and antigen-presenting dendritic cells. Gene expression analysis of IFN-ß-treated bone marrow macrophages (CD11b(+)) identified modulation of genes affecting T cell proliferation and Th17 differentiation. CONCLUSIONS: We conclude that IFN-ß acts to suppress the generation of autoimmune-inducing Th17 cells during the development of disease as well as modulating pro-inflammatory mediators.

Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity.

Gene expression profiling of rheumatoid arthritis (RA) and osteoarthritis (OA) joint tissue samples provides a unique insight into the gene signatures involved in disease development and progression. Fibroblast-like synovial (FLS) cells were obtained from RA, OA and control trauma joint tissues (non-RA, non-OA) and RNA was analyzed by Affymetrix microarray. Thirty-four genes specific to RA and OA FLS cells were identified (P<0.05). HOXD10, HOXD11, HOXD13, CCL8 and LIM homeobox 2 were highly and exclusively expressed in RA and CLU, sarcoglycan-gamma, GPR64, POU3F3, peroxisome proliferative activated receptor-gamma and tripartite motif-containing 2 were expressed only in OA. The data also revealed expression heterogeneity for patients with the same disease. To address disease heterogeneity in RA FLS cells, we examined the effects of clinical disease parameters (Health Assessment Questionnaire (HAQ) score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF)) and drug therapies (methotrexate/prednisone) on RA FLS cell gene expression. Eight specific and unique correlations were identified: human leukocyte antigen (HLA)-DQA2 with HAQ score; Clec12A with RF; MAB21L2, SIAT7E, HAPLN1 and BAIAP2L1 with CRP level; RGMB and OSAP with ESR. Signature RA FLS cell gene expression profiles may provide insights into disease pathogenesis and have utility in diagnosis, prognosis and drug responsiveness.

Synergy between paclitaxel plus an exogenous methyl donor in the suppression of murine demyelinating diseases.

Progressive demyelination in multiple sclerosis (MS) reflects the negative balance between myelin damage and repair due to physical and molecular barriers, such as astrocytic glial scars, between oligodendrocytes and target neurons. In this paper, we show that combination therapy with paclitaxel (Taxol) plus the universal methyl-donor, vitamin B12CN (B12CN), dramatically limits progressive demyelination, and enhances remyelination in several independent, immune and nonimmune, in vivo and in vitro model systems. Combination therapy significantly reduced clinical signs of EAE in SJL mice, as well as the spontaneously demyelinating ND4 transgenic mouse. Astrocytosis was normalised in parallel to ultrastructural and biochemical evidence of remyelination. The combination therapy suppressed T cell expansion, reduced IFN-gamma, while enhancing IFN-beta and STAT-1 expression, STAT-1 phosphorylation and methylation of STAT-1 and MBP in the brain. Paclitaxel/B12CN has nearly identical effects to the previously described combination of IFN-beta/ B12CN, whose clinical usefulness is transient because of IFN-neutralising antibodies, not observed (or expected) with the present drug combination. This report provides a mechanistic foundation for the development of a new therapeutic strategy in humans with MS.

Interferons and viruses: signaling for supremacy.

Interferon (IFN)-alpha and IFN-beta are critical mediators of host defense against microbial challenges, directly interfering with viral infection and influencing both the innate and adaptive immune responses. IFNs exert their effects in target cells through the activation of a cell-surface receptor, leading to a cascade of signaling events that determine transcriptional and translation regulation. Understanding the circuitry associated with IFN-mediated signal transduction that leads to a specific biological outcome has been a major focus of our laboratory. Through the efforts of graduate students, postdoctoral fellows, a skilled research technologist, and important collaborations with investigators elsewhere, we have provided some insights into the complexity of the IFN system-and the elegance and simplicity of how protein-protein interactions define biological function.

Discoidin domain receptor 1 isoform-a (DDR1alpha) promotes migration of leukocytes in three-dimensional collagen lattices.

Although integrins are crucial for migration of leukocytes through endothelium, integrin-independent mechanisms appear to take over and mediate the migration of leukocytes through extracellular matrix (ECM) in a three-dimensional tissue microenvironment. Discoidin domain receptor (DDR) 1 is a receptor tyrosine kinase activated by collagen, the most abundant ECM protein. In the present study, we detected that peripheral blood mononuclear cells (PBMC) and polymorphonuclear neutrophils were induced to express DDR1 after incubation in RPMI 1640. The expression level of DDR1 in PBMC was increased further by stimulation with tumor necrosis factor-alpha, interleukin-1beta, granulocyte-macrophage colony-stimulating factor, lipopolysaccharide, or phytohemagglutinin, but not with interferon-gamma. In vivo, DDR1 mRNA was detectable in mononuclear leukocytes infiltrating human renal tumor tissue. Among three DDR1 isoforms, DDR1alpha was the major transcript in leukocytes. Functionally, overexpression of either DDR1alpha or DDR1beta in THP-1 cells resulted in increased adherence to collagen-coated plates in a beta1-integrin independent manner. However, only DDR1alpha-, but not DDR1beta-, overexpressing cells exhibited marked pseudopod extension and migrated successfully through three-dimensional collagen lattices. Consequently, we propose that the interaction of DDR1alpha with collagen of the ECM results in a requisite intracellular signaling that enables leukocytes to migrate in a tissue microenvironment and participate in host defense.

Effects of human IL-8 isoforms on bovine neutrophil function in vitro.

Interleukin 8 (IL-8) is a potent chemotactic and activating agent for human neutrophils and bovine IL-8 is chemotactic for bovine neutrophils; however, it is unclear whether IL-8 activates bovine neutrophils. Two isoforms of human recombinant (hr) IL-8 protein (77 and 72 amino acid) were used to stimulate bovine neutrophils in vitro. Bovine neutrophils exhibited significant migration in the presence of 0.1, 0.5, 1.0 and 5.0ngml(-1) hr IL-8 when incubated for 30min at 37 degrees C in a modified Boyden chamber assay. Both the 77 and 72 aa forms were equally effective in inducing migration in this assay. At the highest doses of IL-8 examined (1 and 5ngml(-1)), migration was similar to migration in the presence of 20% zymosan-activated serum (ZAS) or 12h lipopolysaccharide (LPS)-stimulated blood monocyte supernatants (CM). Significant (p<0. 05) release of alkaline phosphatase (ALK-P) (from specific granules) occurred but myeloperoxidase (MPO) release and superoxide anion production were not enhanced in bovine neutrophils by either form of hrIL-8 at any of the doses tested. Significant (p<0.05) alkaline phosphatase release was observed in the presence of 10 and 100ngml(-1) for the 72 aa form of IL-8 and only at the higher dose for the 77 aa form of IL-8. The ZAS and CM significantly enhanced neutrophil degranulation of ALK-P and MPO as well as inducing superoxide anion production. These results suggest that IL-8 may play a role in both neutrophil recruitment and activation during bovine inflammatory processes.

A preliminary study on the usefulness of huIL-8 in cervical relaxation of the ewe for artificial insemination and for embryo transfer.

The efficacy of using human interleukin 8 (huIL-8) as an agent for inducing cervical relaxation in estrous and diestrous sheep was assessed in a small pilot study. Multiparous, estrus-synchronized ewes were treated for either 2 or 5 consecutive days with vaginal suppositories with or without 5 micrograms cytokine. Cervical penetration with an insemination instrument was then assessed in vivo. After euthanasia, physical, histological and enzymological properties of the cervix were examined. Treatment of diestrous sheep with huIL-8 did not result in recruitment of neutrophils into the cervix. Treatment of estrous sheep with huIL-8 usually led to neutrophil recruitment to the cervix and to either full or partial penetration of the cervix. However, some animals receiving placebo treatment had neutrophil infiltration of both the vagina and cervix and, in one of these, partial penetration of the cervix was also achieved. Thus, treatment with IL-8 as the sole agent in the vaginal suppository was not sufficient to relax the cervix of the nonpregnant ewe in this study.

Comparison of in vitro function of neutrophils from cattle deficient in plasma factor XI activity and from normal animals.

Cattle, homozygous for the genetic disorder of factor XI (FXI) deficiency, exhibit less than 2% of normal plasma FXI activity, display an increased bleeding tendency and are more prone to infectious diseases. FXI is one of the protein components of the contact activation system of coagulation that assembles on the surface of circulating neutrophils. Because of the central role of neutrophils in inflammation, the in vitro responses of neutrophils from normal and FXI deficient cattle were compared. Neutrophil degranulation was evaluated by measuring the release of myeloperoxidase and alkaline phosphatase, and the respiratory burst was evaluated by determining superoxide anion production. Neutrophils from FXI deficient animals exhibited a significant increase (P < 0.05) in the spontaneous release of granule contents compared to the cells from normal cattle. Following stimulation with C5a complement derived from normal serum, the neutrophils from the FXI deficient animals exhibited a greater increase (P < 0.05) in both alkaline phosphatase release and superoxide production. In these neutrophils, following stimulation with C3b complement from normal serum, the relative increase in myeloperoxidase release compared to the unstimulated neutrophils was lower than that observed in the neutrophils from normal animals. There was minimal superoxide production in unactivated neutrophils from either normal or FXI deficient cattle and the response to phorbol ester stimulation was similar in both groups of animals. The C5a complement from FXI deficient serum was more effective (P < 0.05) in stimulating alkaline phosphatase release and superoxide production in normal neutrophils than the equivalent fraction from FXI deficient serum while the C3b complement from the FXI deficient serum was less effective than the normal serum fraction at inducing myeloperoxidase release from normal neutrophils. The results indicate that the differences in the in vitro neutrophil function are likely related to a variation in the function of the contact activation system on the neutrophil surface between normal and FXI deficient animals.