Multi-modal assessment of long-term erythropoietin treatment after neonatal hypoxic-ischemic injury in rat brain.

Erythropoietin (EPO) has been recognized as a neuroprotective agent. In animal models of neonatal brain injury, exogenous EPO has been shown to reduce lesion size, improve structure and function. Experimental studies have focused on short course treatment after injury. Timing, dose and length of treatment in preterm brain damage remain to be defined. We have evaluated the effects of high dose and long-term EPO treatment in hypoxic-ischemic (HI) injury in 3 days old (P3) rat pups using histopathology, magnetic resonance imaging (MRI) and spectroscopy (MRS) as well as functional assessment with somatosensory-evoked potentials (SEP). After HI, rat pups were assessed by MRI for initial damage and were randomized to receive EPO or vehicle. At the end of treatment period (P25) the size of resulting cortical damage and white matter (WM) microstructure integrity were assessed by MRI and cortical metabolism by MRS. Whisker elicited SEP were recorded to evaluate somatosensory function. Brains were collected for neuropathological assessment. The EPO treated animals did not show significant decrease of the HI induced cortical loss at P25. WM microstructure measured by diffusion tensor imaging was improved and SEP response in the injured cortex was recovered in the EPO treated animals compared to vehicle treated animals. In addition, the metabolic profile was less altered in the EPO group. Long-term treatment with high dose EPO after HI injury in the very immature rat brain induced recovery of WM microstructure and connectivity as well as somatosensory cortical function despite no effects on volume of cortical damage. This indicates that long-term high-dose EPO induces recovery of structural and functional connectivity despite persisting gross anatomical cortical alteration resulting from HI.

CD47 knockout mice exhibit improved recovery from spinal cord injury.

Recent data have implicated thrombospondin-1 (TSP-1) signaling in the acute neuropathological events that occur in microvascular endothelial cells (ECs) following spinal cord injury (SCI) (Benton et al., 2008b). We hypothesized that deletion of TSP-1 or its receptor CD47 would reduce these pathological events following SCI. CD47 is expressed in a variety of tissues, including vascular ECs and neutrophils. CD47 binds to TSP-1 and inhibits angiogenesis. CD47 also binds to the signal regulatory protein (SIRP)α and facilitates neutrophil diapedesis across ECs to sites of injury. After contusive SCI, TSP-1(-/-) mice did not show functional improvement compared to wildtype (WT) mice. CD47(-/-) mice, however, exhibited functional locomotor improvements and greater white matter sparing. Whereas targeted deletion of either CD47 or TSP-1 improved acute epicenter vascularity in contused mice, only CD47 deletion reduced neutrophil diapedesis and increased microvascular perfusion. An ex vivo model of the CNS microvasculature revealed that CD47(-/-)-derived microvessels (MVs) prominently exhibit adherent WT or CD47(-/-) neutrophils on the endothelial lumen, whereas WT-derived MVs do not. This implicates a defect in diapedesis mediated by the loss of CD47 expression on ECs. In vitro transmigration assays confirmed the role of SIRPα in neutrophil diapedesis through EC monolayers. We conclude that CD47 deletion modestly, but significantly, improves functional recovery from SCI via an increase in vascular patency and a reduction of SIRPα-mediated neutrophil diapedesis, rather than the abrogation of TSP-1-mediated anti-angiogenic signaling.

Psychophysiological activation during preparation, performance, and recovery in high- and low-anxious music students

The present study provides a comprehensive view of (a) the time dynamics of the psychophysiological responding in performing music students (n = 66) before, during, and after a private and a public performance and (b) the moderating effect of music performance anxiety (MPA). Heart rate (HR), minute ventilation (VE), and all affective and somatic self-report variables increased in the public session compared to the private session. Furthermore, the activation of all variables was stronger during the performances than before or after. Differences between phases were larger in the public than in the private session for HR, VE, total breath duration, anxiety, and trembling. Furthermore, while higher MPA scores were associated with higher scores and with larger changes between sessions and phases for self-reports, this association was less coherent for physiological variables. Finally, self-reported intra-individual performance improvements or deteriorations were not associated with MPA. This study makes a novel contribution by showing how the presence of an audience influences low- and high-anxious musicians' psychophysiological responding before, during and after performing. Overall, the findings are more consistent with models of anxiety that emphasize the importance of cognitive rather than physiological factors in MPA.

Visual activity predicts auditory recovery from deafness after adult cochlear implantation.

Modern cochlear implantation technologies allow deaf patients to understand auditory speech; however, the implants deliver only a coarse auditory input and patients must use long-term adaptive processes to achieve coherent percepts. In adults with post-lingual deafness, the high progress of speech recovery is observed during the first year after cochlear implantation, but there is a large range of variability in the level of cochlear implant outcomes and the temporal evolution of recovery. It has been proposed that when profoundly deaf subjects receive a cochlear implant, the visual cross-modal reorganization of the brain is deleterious for auditory speech recovery. We tested this hypothesis in post-lingually deaf adults by analysing whether brain activity shortly after implantation correlated with the level of auditory recovery 6 months later. Based on brain activity induced by a speech-processing task, we found strong positive correlations in areas outside the auditory cortex. The highest positive correlations were found in the occipital cortex involved in visual processing, as well as in the posterior-temporal cortex known for audio-visual integration. The other area, which positively correlated with auditory speech recovery, was localized in the left inferior frontal area known for speech processing. Our results demonstrate that the visual modality's functional level is related to the proficiency level of auditory recovery. Based on the positive correlation of visual activity with auditory speech recovery, we suggest that visual modality may facilitate the perception of the word's auditory counterpart in communicative situations. The link demonstrated between visual activity and auditory speech perception indicates that visuoauditory synergy is crucial for cross-modal plasticity and fostering speech-comprehension recovery in adult cochlear-implanted deaf patients.

Ectopic pacing at physiological rate improves postanoxic recovery of the developing heart.

Recently, rapid and transient cardiac pacing was shown to induce preconditioning in animal models. Whether the electrical stimulation per se or the concomitant myocardial ischemia affords such a protection remains unknown. We tested the hypothesis that chronic pacing of a cardiac preparation maintained in a normoxic condition can induce protection. Hearts of 4-day-old chick embryos were electrically paced in ovo over a 12-h period using asynchronous and intermittent ventricular stimulation (5 min on-10 min off) at 110% of the intrinsic rate. Sham (n = 6) and paced hearts (n = 6) were then excised, mounted in vitro, and subjected successively to 30 min of normoxia (20% O(2)), 30 min of anoxia (0% O(2)), and 60 min of reoxygenation (20% O(2)). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout the experiment. Reoxygenation-induced chrono-, dromo-, and inotropic disturbances, incidence of arrhythmias, and changes in electromechanical delay (EMD) in atria and ventricle were systematically investigated in sham and paced hearts. Under normoxia, the isolated heart beat spontaneously and regularly, and all baseline functional parameters were similar in sham and paced groups (means +/- SD): heart rate (190 +/- 36 beats/min), P-R interval (104 +/- 25 ms), mechanical atrioventricular propagation (20 +/- 4 mm/s), ventricular shortening velocity (1.7 +/- 1 mm/s), atrial EMD (17 +/- 4 ms), and ventricular EMD (16 +/- 2 ms). Under anoxia, cardiac function progressively collapsed, and sinoatrial activity finally stopped after approximately 9 min in both groups. During reoxygenation, paced hearts showed 1) a lower incidence of arrhythmias than sham hearts, 2) an increased rate of recovery of ventricular contractility compared with sham hearts, and 3) a faster return of ventricular EMD to basal value than sham hearts. However, recovery of heart rate, atrioventricular conduction, and atrial EMD was not improved by pacing. Activity of all hearts was fully restored at the end of reoxygenation. These findings suggest that chronic electrical stimulation of the ventricle at a near-physiological rate selectively alters some cellular functions within the heart and constitutes a nonischemic means to increase myocardial tolerance to a subsequent hypoxia-reoxygenation.

Defective TNF-alpha-mediated hepatocellular apoptosis and liver damage in acidic sphingomyelinase knockout mice

This study addressed the contribution of acidic sphingomyelinase (ASMase) in TNF-alpha-mediated hepatocellular apoptosis. Cultured hepatocytes depleted of mitochondrial glutathione (mGSH) became sensitive to TNF-alpha, undergoing a time-dependent apoptotic cell death preceded by mitochondrial membrane depolarization, cytochrome c release, and caspase activation. Cyclosporin A treatment rescued mGSH-depleted hepatocytes from TNF-alpha-induced cell death. In contrast, mGSH-depleted hepatocytes deficient in ASMase were resistant to TNF-alpha-mediated cell death but sensitive to exogenous ASMase. Furthermore, although in vivo administration of TNF-alpha or LPS to galactosamine-pretreated ASMase(+/+) mice caused liver damage, ASMase(-/-) mice exhibited minimal hepatocellular injury. To analyze the requirement of ASMase, we assessed the effect of glucosylceramide synthetase inhibition on TNF-alpha-mediated apoptosis. This approach, which blunted glycosphingolipid generation by TNF-alpha, protected mGSH-depleted ASMase(+/+) hepatocytes from TNF-alpha despite enhancement of TNF-alpha-stimulated ceramide formation. To further test the involvement of glycosphingolipids, we focused on ganglioside GD3 (GD3) because of its emerging role in apoptosis through interaction with mitochondria. Analysis of the cellular redistribution of GD3 by laser scanning confocal microscopy revealed the targeting of GD3 to mitochondria in ASMase(+/+) but not in ASMase(-/-) hepatocytes. However, treatment of ASMase(-/-) hepatocytes with exogenous ASMase induced the colocalization of GD3 and mitochondria. Thus, ASMase contributes to TNF-alpha-induced hepatocellular apoptosis by promoting the mitochondrial targeting of glycosphingolipids.

State of Iowa Long-Term Economic Recovery Strategy

The "State of Iowa Long-Term Economic Recovery Strategy" was prepared for the Economic Development Administration, U.S. Department of Commerce. In July, 2008 Iowa received a $3 million grant from the Economic Development Administration to create an Economic Recovery Strategy for recovering from the devastating floods and tornadoes that impacted the state earlier that summer. This report outlines the final version of that strategy. It includes the methods, goals, objectives, measures and key projects that the state has undertaken and will continue into the future to ensure the state‘s complete recovery.

Iowa Disaster Recovery Framework

This Iowa Disaster Recovery Framework (IDRF) is meant to detail a lasting, flexible structure and system to coordinate and manage disaster recovery in the long-term. The IDRF provides a structure to engage stakeholders such as individual Iowans, local and tribal governments, businesses, voluntary, faith-based and community organizations as well as state and federal agencies to identify and resolve recovery challenges both before and after disaster events. It applies to all disasters, recovery partners, and recovery activities.

Iowa Disaster Recovery Tabletop Exercise - After Action Report / Improvement Plan

On June 24, 2010, the Rebuild Iowa Office (RIO) held a discussion-based tabletop exercise for the purpose of creating a framework to support disaster recovery coordination within the State of Iowa. The purpose of this report is to provide an overview of the tabletop exercise, summarize and analyze exercise results, identify strengths which should be maintained and built upon, identify areas for further improvement, and support development of recommendations and corrective actions.

Rebuild Iowa Office Federal Recovery Framework Recommendations, Updated August 31, 2010.

The Rebuild Iowa Office and its' state and local partners recommendations about improving and streamlining the state and federal disaster recovery framework.

Supplement Information to the August 2008 Infrastructure and Transportation Task Force Report, August 2008

The Rebuild Iowa Infrastructure and Transportation Task Force is acutely aware of the critical role infrastructure plays in Iowa’s communities, the lives of the residents, and the economic well-being of the state. With encouragement to the Rebuild Iowa Advisory Commission (RIAC) for its consideration of great need for infrastructure and transportation repairs, the Task Force provides its assessment and recommendations. As the RIAC fulfills its obligations to guide the recovery and reconstruction in Iowa, infrastructure and transportation must be recognized for its impact on all Iowans. The tornadoes, storms, and floods were devastating to infrastructure and transportation systems across the state. The damage did not distinguish between privately-owned and public assets. The significance of the damage emerges further with the magnitude of the damage estimates. Infrastructure includes components that some might initially overlook, such as communication systems, landfills, and water treatment. The miles of damaged roads and bridges are more evident to many Iowans. Given the reliance on infrastructure systems, many repairs are already underway, though gaps have emerged in the funding for repairs to certain infrastructure systems. Supplement Information to the August 2008

Supplemental Information to the August 2008 Public Health and Health Care Task Force Report, August 2008

The Rebuild Iowa Public Health and Health Care Task Force respectfully submits its report to the Rebuild Iowa Advisory Commission (RIAC) for its consideration of the impacts of the tornadoes, storms, and flooding on Iowans. As the RIAC fulfills its obligations to guide the recovery and reconstruction in Iowa, the impact on the health and well-being of Iowans should be of primary concern. With many areas of the state experiencing devastating damage to their communities, public health and health care are but one of the major challenges. There are critical immediate needs to address the health, safety, and well-being of affected Iowans. This report provides background information on the damages incurred in Iowa from the disasters and additional context for policy and rebuilding discussions. It also offers recommendations to the RIAC for steps that might be taken to address these significant and important challenges.

Education Task Force Report, August 2008

The Rebuild Iowa Public Health and Health Care Task Force respectfully submits its report to the Rebuild Iowa Advisory Commission (RIAC) for its consideration of the impacts of the tornadoes, storms, and flooding on Iowans. As the RIAC fulfills its obligations to guide the recovery and reconstruction in Iowa, the impact on the health and well-being of Iowans should be of primary concern. With many areas of the state experiencing devastating damage to their communities, public health and health care are but one of the major challenges. There are critical immediate needs to address the health, safety, and well-being of affected Iowans. This report provides background information on the damages incurred in Iowa from the disasters and additional context for policy and rebuilding discussions. It also offers recommendations to the RIAC for steps that might be taken to address these significant and important challenges.

Education Task Force Report, August 2008

The Rebuild Iowa Education Task Force is composed of Iowans with experience and expertise related to the impact of the tornadoes, storms, and floods of 2008 on the educational system in Iowa. The massive damage greatly impacted educational facilities and enrollment, resulting in thousands of displaced students and significant long-term rebuilding needs. In addition, the education system is a “community center,” and in many ways acts as a first responder to Iowans experiencing the disasters. It is important to also recognize this role and the need for “non-educational” (and often non-quantifiable) supports as a part of the overall recovery effort. There are a few parts of the state that sustained significant structural and other damage as a result of the disasters. However, many school districts and educational institutions throughout the state experienced damage that resulted in re-allocating building usage, enrollment issues (because of housing and relocation issues in the community), or use of school facilities to assist in the recovery efforts (by housing displaced community agencies and providing temporary shelter for displaced Iowans). At this time, damage estimates are only estimates and numbers are revised often. Estimates of damage are being developed by multiple agencies, including FEMA, the Iowa Department of Education, insurance companies, and schools themselves, since there are many different types of damage to be assessed and repaired. In addition to structural damage, educational institutions and communities are trying to find ways to quantify sometimes unquantifiable data, such as future revenue capabilities, population declines, and impact on mental health in the long-term. The data provided in this report is preliminary and as up to date as possible; information is updated on a regular basis as assessments continue and damage estimates are finalized.

Supplemental Information to the August 2008 Education Task Force Report, August 2008

The Rebuild Iowa Education Task Force is composed of Iowans with experience and expertise related to the impact of the tornadoes, storms, and floods of 2008 on the educational system in Iowa. The massive damage greatly impacted educational facilities and enrollment, resulting in thousands of displaced students and significant long-term rebuilding needs. In addition, the education system is a “community center,” and in many ways acts as a first responder to Iowans experiencing the disasters. It is important to also recognize this role and the need for “non-educational” (and often non-quantifiable) supports as a part of the overall recovery effort. There are a few parts of the state that sustained significant structural and other damage as a result of the disasters. However, many school districts and educational institutions throughout the state experienced damage that resulted in re-allocating building usage, enrollment issues (because of housing and relocation issues in the community), or use of school facilities to assist in the recovery efforts (by housing displaced community agencies and providing temporary shelter for displaced Iowans). At this time, damage estimates are only estimates and numbers are revised often. Estimates of damage are being developed by multiple agencies, including FEMA, the Iowa Department of Education, insurance companies, and schools themselves, since there are many different types of damage to be assessed and repaired. In addition to structural damage, educational institutions and communities are trying to find ways to quantify sometimes unquantifiable data, such as future revenue capabilities, population declines, and impact on mental health in the long-term. The data provided in this report is preliminary and as up to date as possible; information is updated on a regular basis as assessments continue and damage estimates are finalized. Supplemental Information to the August 2008 Education Task Force Report