Neurorehabilitation across the Continuum: From the Neurocritical care unit to home.

Children admitted to neurocritical care units often experience new neurodevelopmental disabilities due to both their acquired neurologic injuries and deconditioning from prolonged hospitalizations. Rehabilitation for critically ill children is multifactorial and begins in the intensive care unit itself. The goals of rehabilitation include prevention of complications associated with immobilization and evolving tone, comprehensive evaluation and treatment of functional deficits, and implementation of adaptive strategies with the goal of maximizing recovery. As a child progresses along the medical continuum from the neurocritical care unit to acute care to post-hospitalization settings, their rehabilitative needs and interventions should also evolve. A child in the neurocritical care unit is likely to have sustained an acquired brain injury. Whether resulting from traumatic or non-traumatic causes, all etiologies of pediatric acquired brain injury can result in significant challenges for the child and their family. Post-intensive care syndrome-pediatrics is a clinical construct that that systematically organizes the range of physical, cognitive, psychological, and social symptoms that emerge in both a child and their family members following a critical illness. Ideally, outpatient care for this population evaluates and supports all areas of post-intensive care syndrome-pediatrics through an interdisciplinary clinical care model. Proactive and comprehensive rehabilitation across the continuum provides the opportunity to support the child and their family in all areas affected, thereby minimizing distress, maximizing function, and optimizing outcomes.

Group A Streptococcus-Induced Activation of Human Plasminogen Is Required for Keratinocyte Wound Retraction and Rapid Clot Dissolution.

Invasive outcomes of Group A Streptococcus (GAS) infections that involve damage to skin and other tissues are initiated when these bacteria colonize and disseminate via an open wound to gain access to blood and deeper tissues. Two critical GAS virulence factors, Plasminogen-Associated M-Protein (PAM) and streptokinase (SK), work in concert to bind and activate host human plasminogen (hPg) in order to create a localized proteolytic environment that alters wound-site architecture. Using a wound scratch assay with immortalized epithelial cells, real-time live imaging (RTLI) was used to examine dynamic effects of hPg activation by a PAM-containing skin-trophic GAS isolate (AP53R+S-) during the course of infection. RTLI of these wound models revealed that retraction of the epithelial wound required both GAS and hPg. Isogenic AP53R+S- mutants lacking SK or PAM highly attenuated the time course of retraction of the keratinocyte wound. We also found that relocalization of integrin ß1 from the membrane to the cytoplasm occurred during the wound retraction event. We devised a combined in situ-based cellular model of fibrin clot-in epithelial wound to visualize the progress of GAS pathogenesis by RTLI. Our findings showed GAS AP53R+S- hierarchically dissolved the fibrin clot prior to the retraction of keratinocyte monolayers at the leading edge of the wound. Overall, our studies reveal that localized activation of hPg by AP53R+S- via SK and PAM during infection plays a critical role in dissemination of bacteria at the wound site through both rapid dissolution of the fibrin clot and retraction of the keratinocyte wound layer.

Scaling-up Normative Change Interventions for Adolescent and Youth Reproductive Health: An Examination of the Evidence.

Adolescent and youth reproductive health (AYRH) outcomes are influenced by factors beyond individual control. Increasingly, interventions are seeking to influence community-level normative change to support healthy AYRH behaviors. While evidence is growing of the effectiveness of AYRH interventions that include normative change components, understanding on how to achieve scale-up and wider impact of these programs remains limited. We analyzed peer-reviewed and gray literature from 2000 to 2017 describing 42 AYRH interventions with community-based normative change components that have scaled-up in low/middle-income countries. Only 13 of 42 interventions had significant scale-up documentation. We compared scale-up strategies, scale-up facilitators and barriers, and identified recommendations for future programs. All 13 interventions addressed individual, interpersonal, and community-level outcomes, such as community attitudes and behaviors related to AYRH. Scale-up strategies included expansion via new organizations, adapting original intervention designs, and institutionalization of activities into public-sector and/or nongovernmental organization structures. Four overarching factors facilitated or inhibited scale-up processes: availability of financial and human resources, transferability of intervention designs and materials, substantive community and government-sector partnerships, and monitoring capacity. Scaling-up multifaceted normative change interventions is possible but not well documented. The global AYRH community should prioritize documentation of scale-up processes and measurement to build evidence and inform future programming.

Chemical sympathectomy increases susceptibility to ocular herpes simplex virus type 1 infection.

The cornea is one of the most highly innervated tissues in the mammalian host. We hypothesized changes to cornea innervation through chemical sympathectomy would significantly alter the host response to the neurotropic viral pathogen, herpes simplex virus type 1 (HSV-1) following ocular infection. Mice treated with 6-hydroxydopamine hydrobromide displayed reduced tyrosine hydroxylase-positive fibers residing in the cornea. Sympathectomized mice were also found to show a transient rise in virus recovered in infected tissues and succumbed to infection in greater numbers. Whereas there were no differences in infiltrating leukocyte populations including HSV-1-specific cytotoxic T lymphocytes in the infected tissue, an increase in substance P and a decrease in IFN-gamma levels in the trigeminal ganglion but not brain stem of sympathectomized mice were noted. Sympathectomized mice treated with the neurokinin-1 receptor antagonist L703,606 had delayed mortality implicating the involvement of substance P in HSV-1-mediated death.