Emergency preparedness of families of children with developmental disabilities: what public health and safety emergency planners need to know.

OBJECTIVE: To assess the emergency preparedness knowledge, behaviors, and training needs of families of children with developmental disabilities (DD). DESIGN: An online survey. PARTICIPANTS: A sample of 314 self-selecting US parents/guardians of children with DD, aged birth-21 years. MAIN OUTCOME MEASURES: 1) Preparedness self-assessment; 2) self-report regarding the extent to which families followed 11 specific preparedness action steps derived from publicly available preparedness guides; and 3) parent training and support needs. RESULTS: Although most participants assessed themselves to be somewhat to moderately well prepared, even those who reported being "very well prepared" had taken fewer than half of 11 recommended action steps. Most participants expressed a need for preparedness support; virtually all the respondents felt that training was either important or very important. CONCLUSIONS: Children with disabilities are known to be particularly vulnerable to negative disaster impacts. Overall, parents in this study appeared under-prepared to meet family disaster needs, although they recognized its importance. The results suggest opportunities and methods for public health and safety planning, education and outreach to parents of children with DD who would benefit from targeted training such as information and skill building to develop effective family preparedness plans and connections to local emergency management and responders.

Emergency preparedness of families of children with developmental disabilities: what public health and safety emergency planners need to know.

OBJECTIVE: To assess the emergency preparedness knowledge, behaviors, and training needs of families of children with developmental disabilities (DD). DESIGN: An online survey. PARTICIPANTS: A sample of 314 self-selecting US parents/guardians of children with DD, aged birth-21 years. MAIN OUTCOME MEASURES: 1) Preparedness self-assessment; 2) self-report regarding the extent to which families followed 11 specific preparedness action steps derived from publicly available preparedness guides; and 3) parent training and support needs. RESULTS: Although most participants assessed themselves to be somewhat to moderately well prepared, even those who reported being "very well prepared" had taken fewer than half of 11 recommended action steps. Most participants expressed a need for preparedness support; virtually all the respondents felt that training was either important or very important. CONCLUSIONS: Children with disabilities are known to be particularly vulnerable to negative disaster impacts. Overall, parents in this study appeared under-prepared to meet family disaster needs, although they recognized its importance. The results suggest opportunities and methods for public health and safety planning, education and outreach to parents of children with DD who would benefit from targeted training such as information and skill building to develop effective family preparedness plans and connections to local emergency management and responders.

Educating first responders to provide emergency services to individuals with disabilities.

OBJECTIVE: Individuals with disabilities experience more negative outcomes due to natural and manmade disasters and emergencies than do people without disabilities. This vulnerability appears to be due in part to knowledge gaps among public health and safety emergency planning and response personnel (responders). We assessed the effectiveness of an online program to increase emergency responder knowledge about emergency planning and response for individuals with disabilities. METHODS: Researchers developed an online course designed to teach public health, emergency planning and management, and other first response personnel about appropriate, efficient, and equitable emergency planning, response, interaction, and communication with children and adults with disabilities before, during, and after disasters or emergencies. Course features included an ongoing storyline, exercises embedded in the form of real-life scenarios, and game-like features such as points and timed segments. RESULTS: Evaluation measures indicated significant pre- to post-test gains in learner knowledge and simulated applied skills. CONCLUSION: An online program using scenarios and simulations is an effective way to make disability-related training available to a wide variety of emergency responders across geographically disparate areas.

LIGHT (TNFSF14/CD258) is a decisive factor for recovery from experimental autoimmune encephalomyelitis.

The TNF superfamily ligand LIGHT (lymphotoxin-like, exhibits inducible expression and competes with HSV glycoprotein D for herpesvirus entry mediator [HVEM], a receptor expressed by T lymphocytes) has been shown to play a role in T cell costimulation and be involved in apoptosis of mononuclear cells. As both T cells and monocytes are key components in the development and progression of experimental autoimmune encephalomyelitis (EAE), we studied the role of LIGHT in EAE. Following immunization with myelin oligodendrocyte glycoprotein peptide (35-55), LIGHT-deficient mice developed severe EAE that resulted in an atypically high mortality rate. Histological examinations revealed intensive activation of microglia/macrophages in the CNS and higher numbers of apoptotic cells within the CNS parenchyma of LIGHT-deficient mice. However, myelin oligodendrocyte glycoprotein peptide-specific CD4(+) T cells from LIGHT-deficient mice showed reduced IFN-γ and IL-17 production and migration. Serum levels of reactive nitrogen intermediates and CNS transcripts of several proinflammatory cytokines and chemokines were also substantially decreased in the absence of LIGHT. EAE adoptive transfer experiments and bone marrow chimeras indicated that expression of LIGHT on donor cells is not required for disease induction. However, its expression on CNS host cells is a decisive factor to limit disease progression and tissue damage. Together, these data show that LIGHT expression is crucially involved in controlling activated macrophages/microglia during autoimmune CNS inflammation.

Central nervous system expression and PET imaging of the translocator protein in relapsing-remitting experimental autoimmune encephalomyelitis.

UNLABELLED: Glial neuroinflammation is associated with the development and progression of multiple sclerosis. PET imaging offers a unique opportunity to evaluate neuroinflammatory processes longitudinally in a noninvasive and clinically translational manner. (18)F-PBR111 is a newly developed PET radiopharmaceutical with high affinity and selectivity for the translocator protein (TSPO), expressed on activated glia. This study aimed to investigate neuroinflammation at different phases of relapsing-remitting (RR) experimental autoimmune encephalomyelitis (EAE) in the brains of SJL/J mice by postmortem histologic analysis and in vivo by PET imaging with (18)F-PBR111. METHODS: RR EAE was induced by immunization with PLP(139-151) peptide in complete Freund's adjuvant. Naive female SJL/J mice and mice immunized with saline-complete Freund's adjuvant were used as controls. The biodistribution of (18)F-PBR111 was measured in 13 areas of the central nervous system and compared with PET imaging results during different phases of RR EAE. The extents of TSPO expression and glial activation were assessed with immunohistochemistry, immunofluorescence, and a real-time polymerase chain reaction. RESULTS: There was significant TSPO expression in all of the central nervous system areas studied at the peak of the first clinical episode and, importantly, at the preclinical stage. In contrast, only a few TSPO-positive cells were observed at the second episode. At the third episode, there was again an increase in TSPO expression. TSPO expression was associated with microglial cells or macrophages without obvious astrocyte labeling. The dynamics of (18)F-PBR111 uptake in the brain, as measured by in vivo PET imaging and biodistribution, followed the pattern of TSPO expression during RR EAE. CONCLUSION: PET imaging with the TSPO ligand (18)F-PBR111 clearly reflected the dynamics of microglial activation in the SJL/J mouse model of RR EAE. The results are the first to highlight the discrepancy between the clinical symptoms of EAE and TSPO expression in the brain, as measured by PET imaging at the peaks of various EAE episodes. The results suggest a significant role for PET imaging investigations of neuroinflammation in multiple sclerosis and allow for in vivo follow-up of antiinflammatory treatment strategies.

Evaluation of [¹²³I]-CLINDE as a potent SPECT radiotracer to assess the degree of astroglia activation in cuprizone-induced neuroinflammation.

PURPOSE: The purpose of this study was to assess the feasibility and sensitivity of the high-affinity translocator protein (TSPO) ligand [(123)I]-CLINDE in imaging TSPO changes in vivo and characterise and compare astroglial and TSPO changes in the cuprizone model of demyelination and remyelination in C57BL/6 mice. METHODS: C57BL/6 mice were fed with cuprizone for 4 weeks to induce demyelination followed by 2-4 weeks of standard diet (remyelination). Groups of mice were followed by in vivo single photon emission computed tomography (SPECT)/CT imaging using [(123)I]-CLINDE and uptake correlated with biodistribution, autoradiography, immunohistochemistry, immunofluorescence and real-time polymerase chain reaction (RT-PCR). RESULTS: The uptake of [(123)I]-CLINDE in the brain as measured by SPECT imaging over the course of treatment reflects the extent of the physiological response, with significant increases observed during demyelination followed by a decrease in uptake during remyelination. This was confirmed by autoradiography and biodistribution studies. A positive correlation between TSPO expression and astrogliosis was found and both activated astrocytes and microglial cells expressed TSPO. [(123)I]-CLINDE uptake reflects astrogliosis in brain structures such as corpus callosum, caudate putamen, medium septum and olfactory tubercle as confirmed by both in vitro and in vivo results. CONCLUSION: The dynamics in the cuprizone-induced astroglial and TSPO changes, observed by SPECT imaging, were confirmed by immunofluorescence, RT-PCR and autoradiography. The highly specific TSPO radioiodinated ligand CLINDE can be used as an in vivo marker for early detection and monitoring of a variety of neuropathological conditions using noninvasive brain imaging techniques.

Demyelination caused by the copper chelator cuprizone halts T cell mediated autoimmune neuroinflammation.

Myelin reactive T cells are central in the development of the autoimmune response leading to CNS destruction in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis (EAE). Investigations on the mechanisms underlying the activation and expansion of myelin reactive T have stressed the importance of non-autoimmune conditions impinging the autoimmune repertoire potentially involved in the disease. Here, we show that CNS injury caused by the toxic cuprizone results in the generation of immunoreactivity towards several myelin components. Paradoxically, exposure to CNS injury does not increase the susceptibility to develop EAE, but render mice protected to the pathogenic autoimmune response against myelin antigens.

The innate immune response to adjuvants dictates the adaptive immune response to autoantigens.

To elucidate the role of innate immunity in susceptibility to the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we induced EAE by immunization with spinal cord homogenate (SCH) plus complete Freund adjuvant or carbonyl iron in 3 inbred rat strains. Lewis are considered "susceptible," PVG/c-Rt7a (PVG) as "semisusceptible," and Brown Norway (BN) as "resistant" to EAE. Immunization with SCH-carbonyl iron resulted in clinical disease in all 3 strains, but the pathologic features of EAE in the resistant BN and the semisusceptible PVG rats differed from those in the Lewis and PVG model of EAE induced with SCH-complete Freund adjuvant. In BN and PVG rats, there were numerous inflammatory lesions with prominent involvement of microglia and, to a lesser extent, perivascular macrophages. These data suggest that different levels of activation of the innate immune system by different adjuvants determine whether EAE will or will not develop. Accordingly, the widely accepted scale of susceptibility to EAE development (Lewis > PVG > BN) should be revised because it does not take into account the important contribution of the composition of the adjuvant to the quality and quantity of the innate immune response and, consequently, to the generation and extent of the pathogenic T-cell-mediated, that is, adaptive, autoimmune disease.

Nitric oxide contributes to the resistance of young SJL/J mice to experimental autoimmune encephalomyelitis.

EAE development in SJL/J mice is age and sex dependent: young males are EAE resistant; females and adult males are EAE susceptible. By studying splenocytes' IFNgamma and NO production and the induction or the suppression of actively induced EAE by manipulating NO systemic levels, we provide evidence that the failure of young male SJL/J mice to develop EAE lies in the activation of the innate immune system by the immunising stimulus.