Lung Ultrasound and High-Resolution Computed Tomography in Suspected COVID-19 Patients Admitted to the Emergency Department: A Comparison.

Objective: To analyze the diagnostic accuracy of lung ultrasonography (LUS) and high-resolution computed tomography (HRCT), to detect COVID-19. Materials and Methods: This study recruited all patients admitted to the emergency medicine unit, due to a suspected COVID-19 infection, during the first wave of the COVID-19 pandemic. These patients also who underwent a standardized LUS examination and a chest HRCT. The signs detected by both LUS and HRCT were reported, as well as the sensitivity, specificity, positive predictive value, and negative predictive value for LUS and HRCT. Results: This cohort included 159 patients, 101 (63%) were diagnosed with COVID-19. COVID-19 patients showed more often confluent subpleural consolidations and parenchymal consolidations in lower lung regions of LUS. They also had "ground glass" opacities and "crazy paving" on HRCT, while pleural effusion and pulmonary consolidations were more common in non-COVID-19 patients. LUS had a sensitivity of 0.97 (95% CI 0.92-0.99) and a specificity of 0.24 (95% CI 0.07-0.5) for COVID-19 lung infections. HRCT abnormalities resulted in a 0.98 sensitivity (95% CI 0.92-0.99) and 0.1 specificity (95% CI 0.04-0.23) for COVID-19 lung infections. Conclusion: In this cohort, LUS proved to be a noninvasive, diagnostic tool with high sensitivity for lung abnormalities that were likewise detected by HRCT. Furthermore, LUS, despite its lower specificity, has a high sensitivity for COVID-19, which could prove to be as effective as HRCT in excluding a COVID-19 lung infection.

Health Mindsets in Pediatric Chronic Headache.

OBJECTIVE: Given how frequently youth with chronic headache and migraine experience setbacks in treatment, identifying factors that promote coping and resilience is critical. Mindsets have gained attention as predictors of behavior and targets of intervention across contexts, including health. Health mindsets may help to explain how children with chronic pain interpret and respond to treatment. This study evaluated whether growth health mindsets might relate to adaptive outcomes in patients with chronic pediatric headache. METHODS: Participants were 88 children and adolescents (ages 10-17 years) with headache or migraine contacted following an appointment at a pediatric headache clinic, and their parent. Patients rated their beliefs about health as more fixed versus growth-oriented. They were presented with vignettes depicting hypothetical treatment setbacks and instructed to reflect upon real-life setbacks. Patients completed questionnaires about their cognitive appraisals of setbacks, coping, quality of life, life satisfaction, and functional impairment. RESULTS: The higher children rated their growth health mindsets, the less likely they were to appraise setbacks as threatening and endorse quality-of-life problems. Children with higher growth mindsets reported higher life satisfaction and lower functional disability. There was also an indirect relation between children's mindsets and coping through cognitive appraisals of setbacks as a threat, but not challenge. CONCLUSION: This research extends the health mindsets literature by contributing preliminary evidence of health mindsets as tied to adaptive outcomes in youth with chronic headache. These findings may be of interest to clinicians and parents, as health mindsets may offer an avenue by which resilience is promoted and maladaptive appraisals are minimized.

The positive allosteric modulator at mGlu2 receptors, LY487379, reverses the effects of chronic stress-induced behavioral maladaptation and synaptic dysfunction in the adulthood.

Chronic stress induces maladaptive neural responses in several brain areas including hippocampus. It has been demonstrated that chronic stress exposure induced a downregulation of the putative presynaptic type 2 metabotropic glutamate (mGlu2) receptors, which would reduce the negative feedback role exerted by these receptors. The reduced availability of these receptors would enhance glutamate overflow in the hippocampus, supporting the hypothesis that hippocampal glutamatergic neurotransmission plays a key etiopathological determinant in stress-induced neuropsychiatric disorders. Since modulation of glutamatergic neurotransmission has been shown to represent an interesting pharmacological tool to treat psychiatric disorders, in the present study we have investigated the effects of the mGlu2 receptor positive allosteric modulator (PAM) LY487379. The rational bases of our study were: (a) chronic restraint stress (CRS) application in C57/BALB6 mouse induced a loss of resilience at the behavioral, biochemical, and electrophysiological level; (b) a superimposed familiar stressor (restraint) but not unfamiliar (i.e., forced swim stress) completely reversed the effects of CRS. Using the CRS model, in the present study we have investigated the effects of LY487379, an mGlu2 PAM, as well as a superimposed familiar stressor (acute restraint stress-ARS), on the immobility time at the tail suspension test and electrophysiological profile of glutamatergic transmission in the dentate gyrus (DG).

Stress as risk factor for Alzheimer's disease.

Prolonged stress predisposes susceptible individuals to a number of physiological disorders including cardiovascular disease, obesity and gastrointestinal disorders, as well as psychiatric and neurodegenerative disorders. Preclinical studies have suggested that manipulation of the glucocorticoid milieu can trigger cellular, molecular and behavioral derangement resembling the hallmarks of Alzheimer's Disease (AD). For example, stress or glucocorticoid administration can increase amyloid ß precursor protein and tau phosphorylation which are involved in synaptic dysfunction and neuronal death associated with AD. Although since AD was first described in 1906 at a conference in Tubingen, Germany by Alois Alzheimer our knowledge of neuropathological and neurochemical alterations of AD has been impressively increased, at present, pharmacotherapy is symptomatic at best and has no influence on the progression of the disorder. It is generally believed that most of the drugs developed as disease modifiers have failed in clinical trials because treatment started too late, i.e., after the clinical onset of AD. Because AD pathology begins several years prior to the clinical diagnosis, it is imperative to identify subjects at high risk to develop the disorder. Consequently, the search for putative risk factors has gained importance. ApoE4, diabetes/metabolic syndrome, cardiovascular disorders, and a low cognitive reserve are established risk factors for AD. The focus of this review is on stress and glucocorticoids as potential factors increasing the risk to develop AD.

Maternal mind-mindedness and toddler behavior problems: The moderating role of maternal trauma and posttraumatic stress.

Maternal mind-mindedness (MM) reflects a caregiver's tendency to view a child as an individual with an independent mind. Research has linked higher MM with more favorable parenting and child adaptation. The aim of this study was to examine whether MM was associated with toddlers' behavior problems and competence, and the moderating role of trauma and posttraumatic stress disorder (PTSD) in a sample (N = 212) of adolescent mothers and their toddlers. MM was coded from maternal utterances during free play; mothers completed the University of California at Los Angeles Trauma and Posttraumatic Stress Disorder Reaction Index and reported on children's behavior problems and competence using the Brief Infant-Toddler Social and Emotional Assessment. The majority of mothers (84%) experienced trauma; 45% of these mothers met criteria for partial or full PTSD. Trauma was related to greater behavior problems, and PTSD moderated MM-child functioning relations. When mothers experienced full PTSD, there was no relation between MM and behavior problems. With child competence, when compared to children of mothers with no trauma exposure, children of mothers experiencing partial PTSD symptoms were more likely to have delays in competence when mothers made more MM comments. Results are discussed in light of how MM, in the context of trauma and PTSD, may affect parenting.

Subtle alterations of excitatory transmission are linked to presynaptic changes in the hippocampus of PINK1-deficient mice.

Homozygous or heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene have been linked to early-onset Parkinson's disease (PD). Several neurophysiological studies have demonstrated alterations in striatal synaptic plasticity along with impaired dopamine release in PINK1-deficient mice. Using electrophysiological methods, here we show that PINK1 loss of function causes a progressive increase of spontaneous glutamate-mediated synaptic events in the hippocampus, without influencing long-term potentiation. Moreover, fluorescence analysis reveals increased neurotrasmitter release although our biochemical results failed to detect which presynaptic proteins might be engaged. This study provides a novel role for PINK1 beyond the physiology of nigrostriatal dopaminergic circuit. Specifically, PINK1 might contribute to preserve synaptic function and glutamatergic homeostasis in the hippocampus, a brain region underlying cognition. The subtle changes in excitatory transmission here observed might be a pathogenic precursor to excitotoxic neurodegeneration and cognitive decline often observed in PD. Using electrophysiological and fluorescence techniques, we demonstrate that lack of PINK1 causes increased excitatory transmission and neurotransmitter release in the hippocampus, which might lead to the cognitive decline often observed in Parkinson's disease.

Depression as a mediator of the relation between family functioning and functional disability in youth with chronic headaches.

OBJECTIVE: This retrospective chart review examined a mediation model of parent and family functioning, childhood depression, and functional disability in youth with chronic headaches. Specifically, we evaluated whether depression mediates the relations between protective parenting and functional disability and between family functioning and functional disability. BACKGROUND: Children and adolescents with chronic and recurrent headache report elevated symptoms of depression. Children with chronic pain conditions, including chronic headaches, have also been found to originate from families with greater conflict, poorer cohesion, and lower organizational structure, and impaired family functioning is associated with greater disability in youth with chronic pain. METHODS: Three hundred and eighty-two patients ages 5-17 years who underwent a multidisciplinary evaluation at a tertiary pediatric headache clinic were included in this study. Participants completed a pain intensity rating, the Children's Depression Inventory, and the Functional Disability Inventory. A parent completed the Family Relationship Index and the Adult Responses to Children's Symptoms questionnaires. Structural equation modeling was used to examine a mediation model and several alternative models. RESULTS: Mediation was not supported, but an alternative model with both direct and indirect pathways provided excellent fit to the data: χ2(1) = 0.745, P = .39; comparative fit index = 1.00, root mean square error of approximation = 0.00 (CI: 0.00-0.17). Family functioning (ß = -0.19, P < .01) and protective parenting (ß = 0.17, P < .01) were associated with depression, but not disability. Depression was linked to disability (ß = 0.24, P < .01). There was an indirect pathway from family functioning to depression to disability (ß = -0.05, P < .05). CONCLUSIONS: Family context is an important variable to consider in youth with chronic headaches and disability. While many studies have identified family functioning and depressive symptoms as separately linked to functional impairment, to our knowledge, we are the first to demonstrate depression as an intermediary variable between family dysfunction and disability within the pediatric headache population.

Autonomic dysfunction in pediatric patients with headache: migraine versus tension-type headache.

PURPOSE: To examine symptoms indicating central nervous system (CNS) autonomic dysfunction in pediatric patients with migraine and tension-type headache. METHODS: A retrospective chart review assessed six symptoms (i.e. constipation, insomnia, dizziness, blurry vision, abnormal blood pressure, and cold and clammy palms and soles) indicating central nervous system (CNS) autonomic dysfunction in 231 patients, ages 5-18 years, diagnosed with migraine, tension-type headache (TTH), or Idiopathic Scoliosis (IS). RESULTS: Higher frequencies of "insomnia," "dizziness," and "cold and clammy palms and soles" were found for both migraine and TTH patients compared to the IS control group (P < 0.001). Frequencies of all six symptoms were greater in TTH than migraine patients with "cold and clammy palms and soles" reaching significance (P < 0.001). CONCLUSIONS: The need for prospective research investigating autonomic dysfunction in pediatric headache patients is discussed.

L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors.

Epigenetic mechanisms are involved in the pathophysiology of depressive disorders and are unique potential targets for therapeutic intervention. The acetylating agent L-acetylcarnitine (LAC), a well-tolerated drug, behaves as an antidepressant by the epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors. It caused a rapid and long-lasting antidepressant effect in Flinders Sensitive Line rats and in mice exposed to chronic unpredictable stress, which, respectively, model genetic and environmentally induced depression. In both models, LAC increased levels of acetylated H3K27 bound to the Grm2 promoter and also increased acetylation of NF-ĸB-p65 subunit, thereby enhancing the transcription of Grm2 gene encoding for the mGlu2 receptor in hippocampus and prefrontal cortex. Importantly, LAC reduced the immobility time in the forced swim test and increased sucrose preference as early as 3 d of treatment, whereas 14 d of treatment were needed for the antidepressant effect of chlorimipramine. Moreover, there was no tolerance to the action of LAC, and the antidepressant effect was still seen 2 wk after drug withdrawal. Conversely, NF-ĸB inhibition prevented the increase in mGlu2 expression induced by LAC, whereas the use of a histone deacetylase inhibitor supported the epigenetic control of mGlu2 expression. Finally, LAC had no effect on mGlu2 knockout mice exposed to chronic unpredictable stress, and a single injection of the mGlu2/3 receptor antagonist LY341495 partially blocked LAC action. The rapid and long-lasting antidepressant action of LAC strongly suggests a unique approach to examine the epigenetic hypothesis of depressive disorders in humans, paving the way for more efficient antidepressants with faster onset of action.

Butalbital and pediatric headache: stay off the downward path.

Despite limited evidence from the literature surrounding safety or efficacy, butalbital-containing medicines (BCMs) have maintained their rank as "go-to" prescribed migraine and headache relief drugs in the United States, despite bans on these barbiturates in Germany and other European countries. Providers at the Pediatric Headache Program at Boston Children's Hospital recommend that clinicians prescribe triptan-based medications instead of BCMs, given the known negative side effects of BCMs on the general population, and the uncertain longitudinal trajectory of BCMs on developing brains.

Corticotropin-Releasing Hormone: Biology and Therapeutic Opportunities.

In 1981, Wylie Vale, Joachim Spiess, Catherine Rivier, and Jean Rivier reported on the characterization of a 41-amino-acid peptide from ovine hypothalamic extracts with high potency and intrinsic activity stimulating the secretion of adrenocorticotropic hormone and ß-endorphin by cultured anterior pituitary cells. With its sequence known, this neuropeptide was determined to be a hormone and consequently named corticotropin-releasing hormone (CRH), although the term corticotropin-releasing factor (CRF) is still used and preferred in some circumstances. Several decades have passed since this seminal contribution that opened a new research era, expanding the understanding of the coding of stress-related processes. The characterization of CRH receptors, the availability of CRH agonists and antagonists, and advanced immunocytochemical staining techniques have provided evidence that CRH plays a role in the regulation of several biological systems. The purpose of this review is to summarize the present knowledge of this 41-amino-acid peptide.

Postweaning social isolation and autism-like phenotype: A biochemical and behavioral comparative analysis.

Adolescence is a critical period for brain development. In most mammalian species, disturbances experienced during adolescence constitute a risk factor for several neuropsychiatric disorders. In this study, we compared the biochemical and behavioral profile induced by postweaning social isolation (PWSI) in inbred C57BL/6 N mice with that of BTBR mice, a rodent model of autism spectrum disorders. Male C57BL/6 N mice were either housed in groups of four or isolated from weaning (postnatal day 21) for four weeks before experimental analyses. After weaning, male BTBR mice were housed four per cage and analyzed at 48 days of age. PWSI reduced hippocampal levels of type 2 metabotropic glutamate (mGlu2) receptors, and glucocorticoid and mineralocorticoid receptors. A similar reduction was seen in group-housed BTBR mice. Plasma corticosterone levels in basal conditions were not influenced by PWSI, but were increased in BTBR mice. Social investigation (total and head sniffing) and the number of ultrasonic vocalizations were reduced in both PWSI mice and age-matched group-housed BTBR mice, indicating a lower social responsiveness in both groups of mice. These results suggest that absence of social stimuli during adolescence induces an endophenotype with social deficit features, which mimics the phenotype of a mouse model of autism spectrum disorders.

Brief report of protective factors associated with family and parental well-being during the COVID-19 pandemic in an outpatient child and adolescent psychiatric clinic.

Families of children with mental health challenges may have been particularly vulnerable to emotional distress during the COVID-19 pandemic. This cross-sectional study surveyed 81 parents of children ages 6-17 years receiving mental health treatment in an outpatient clinic during the pandemic. We sought to characterize the impact of the pandemic on family relationships and parental well-being. Additionally, regression and ANCOVA models examined associations between four potentially protective factors-parents' psychological resilience, perceived social support, positive family experiences during the pandemic, and children's use of cognitive or behavioral coping strategies-with family relationships and parental well-being. Findings suggest that families of children with mental health conditions experienced remarkable challenges to family relationships, parental well-being, and parents' perceived capacity to support their children's mental health. Nearly 80% of parents reported a negative impact of the pandemic on their own well-being, and 60% reported reduced ability to support their children's mental health. Simultaneously, protective factors appeared to mitigate the negative impact of the pandemic. Particularly, support within the family (e.g., co-parenting) and from external sources (e.g., mental health services) were associated with better self-reported well-being for parents and their capacity to support their children. Children's use of coping tools, likely enhanced by mental health treatment, was also positively related to better family relationships and parental ability to support children with mental health challenges. Our findings highlight the need for enhancing supports for families at multiple levels including individual skill-building, family-based/parenting support, and community-based support.

Parenting, self-regulation, and treatment adherence in pediatric chronic headache: A self-determination theory perspective.

This study examined parenting factors associated with children's self-regulation and physician-rated treatment adherence using a self-determination theory framework in pediatric chronic headache. Participants were 58 children and adolescents (aged 10-17 years), who underwent initial and follow-up multidisciplinary evaluation at a headache clinic, and their mothers. Regression analyses showed that higher maternal autonomy support and structure were significantly related to children's lower treatment-related reactance and higher adherence. Maternal controllingness had associations in the opposite directions. Children's fear of pain was related to maternal controllingness. Results suggest the importance of parents' provision of clear expectations and engaging children in treatment problem-solving and decision-making.

Risk Factors for Alzheimer's Disease: Focus on Stress.

In vulnerable individuals, chronic and persistent stress is an established risk factor for disorders that are comorbid with Alzheimer's disease (AD), such as hypertension, obesity and metabolic syndrome, and psychiatric disorders. There are no disease-modifying drugs in the treatment of AD, and all phase-3 clinical trials with anti-amyloid drugs (e.g., ß- or γ-secretase inhibitors and monoclonal antibodies) did not meet the primary endpoints. There are many reasons for the lack of efficacy of anti-amyloid drugs in AD, the most likely being a late start of treatment, considering that pathophysiological mechanisms underlying synaptic dysfunction and neuronal death begin several decades before the clinical onset of AD. The identification of risk factors is, therefore, an essential step for early treatment of AD with candidate disease-modifying drugs. Preclinical studies suggest that stress, and the resulting activation of the hypothalamic-pituitary-adrenal axis, can induce biochemical abnormalities reminiscent to those found in autoptic brain samples from individuals affected by AD (e.g., increases amyloid precursor protein and tau hyperphosphorylation). In this review, we will critically analyze the current knowledge supporting stress as a potential risk factor for AD.

Differential activation of the calcium/protein kinase C and the canonical beta-catenin pathway by Wnt1 and Wnt7a produces opposite effects on cell proliferation in PC12 cells.

We examined the effect of Wnt1 and Wnt7a on cell proliferation using undifferentiated PC12 cells, which originate from the neural crest and are widely employed as a neuronal cell model. Heterologous expression of Wnt1 enhanced [3H]thymidine incorporation and expression of cyclin D1 and cylin E in PC12 cells. Opposite effects were observed in PC12 cells expressing Wnt7a. Searching for the mechanisms underlying the opposite effects of Wnt1 and Wnt7a on PC12 cell proliferation, we examined the activation of the canonical beta-catenin/T-cell-lymphoid enhancer-binding protein transcription factor pathway and the 'calcium pathway' by co-transfecting the cells with a reporter gene controlled by either T-cell-lymphoid enhancer-binding protein transcription factor or the calcium-activated transcription factor, NFAT. Wnt1 and Wnt7a activated both pathways, but to a different extent. While Wnt1 preferentially activated the calcium pathway, Wnt7a mainly activated the canonical pathway. Pharmacological inhibition of protein kinase C, which is a component of the calcium pathway, abrogated the increase in cell proliferation induced by Wnt1 without affecting the antiproliferative action of Wnt7a. The action of Wnt7a was instead occluded by lithium ions, which mimic the activation of the canonical pathway, and was largely reduced by Dickkopf-1, which acts as an inhibitor of the canonical pathway. In addition, expression of a constitutively active mutant of beta-catenin potently activated the canonical Wnt pathway and reduced [3H]thymidine incorporation. These data challenge the view that the canonical Wnt pathway invariably supports cell growth and suggest that, at least in PC12 cells, cell proliferation is regulated by the balance between the calcium/protein kinase C pathway and the canonical pathway.

Pharmacological activation of mGlu4 metabotropic glutamate receptors inhibits the growth of medulloblastomas.

Moving from the evidence that activation of type 4 metabotropic glutamate (mGlu4) receptors inhibits proliferation and promotes differentiation of cerebellar granule cell neuroprogenitors, we examined the expression and function of mGlu4 receptors in medulloblastoma cells. mGlu4 receptors were expressed in 46 of 60 human medulloblastoma samples. Expression varied in relation to the histotype (nodular desmoplastic>classic>>large-cell anaplastic) and was inversely related to tumor severity, spreading, and recurrence. mGlu4 receptors were also found in D283med, D341med, and DAOY medulloblastoma cell lines, where receptor activation with the selective enhancer PHCCC inhibited adenylyl cyclase and the phosphatidylinositol-3-kinase pathway without affecting the mitogen-activated protein kinase, Sonic Hedgehog, and Wnt pathways. Interestingly, mGlu4 receptor activation reduced DNA synthesis and cell proliferation in all three cell lines. This effect was abrogated by the phosphatidylinositol-3-kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one]. In in vivo experiments, repeated subcutaneous injections of N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) reduced the growth of D283med and DAOY cell xenografts in nude mice. More remarkably, subcutaneous or intracranial injections of PHCCC during the first week of life prevented the development of medulloblastomas in mice lacking one Patched-1 allele and x-irradiated 1 d after birth. These data suggest that mGlu4 receptor enhancers are promising drugs for the treatment of medulloblastomas.

Nanomolar concentrations of anabolic-androgenic steroids amplify excitotoxic neuronal death in mixed mouse cortical cultures.

The use of anabolic-androgenic steroids (AASs) in the world of sport has raised a major concern for the serious, sometimes life-threatening, side effects associated with these drugs. Most of the CNS effects are of psychiatric origin, and whether or not AASs are toxic to neurons is yet unknown. We compared the effect of testosterone with that of the AASs, 19-nortestosterone (nandrolone), stanozolol, and gestrinone, on excitotoxic neuronal death induced by N-methyl-d-aspartate (NMDA) in primary cultures of mouse cortical cells. In the most relevant experiments, steroids were applied to the cultures once daily during the 4 days preceding the NMDA pulse. Under these conditions, testosterone amplified excitotoxic neuronal death only at very high concentrations (10 muM), whereas it was protective at concentrations of 10 nM and inactive at intermediate concentrations. Low concentrations of testosterone became neurotoxic in the presence of the aromatase inhibitors, i.e. anastrozole and aminoglutethimide, suggesting that the intrinsic toxicity of testosterone was counterbalanced by its aromatization into 17beta-estradiol. As opposed to testosterone, nortestosterone, stanozolol and gestrinone amplified NMDA toxicity at nanomolar concentrations; their action was insensitive to aromatase inhibitors, but was abrogated by the androgen receptor antagonist, flutamide. None of the AASs were toxic in the absence of NMDA. These data suggest that AASs increase neuronal vulnerability to an excitotoxic insult and may therefore facilitate neuronal death associated with acute or chronic CNS disorders.

Morphine Withdrawal Modifies Prion Protein Expression in Rat Hippocampus.

The hippocampus is a vulnerable brain structure susceptible to damage during aging and chronic stress. Repeated exposure to opioids may alter the brain so that it functions normally when the drugs are present, thus, a prolonged withdrawal might lead to homeostatic changes headed for the restoration of the physiological state. Abuse of morphine may lead to Reacting Oxygen Species-induced neurodegeneration and apoptosis. It has been proposed that during morphine withdrawal, stress responses might be responsible, at least in part, for long-term changes of hippocampal plasticity. Since prion protein is involved in both, Reacting Oxygen Species mediated stress responses and synaptic plasticity, in this work we investigate the effect of opiate withdrawal in rats after morphine treatment. We hypothesize that stressful stimuli induced by opiate withdrawal, and the subsequent long-term homeostatic changes in hippocampal plasticity, might modulate the Prion protein expression. Our results indicate that abstinence from the opiate induced a time-dependent and region-specific modification in Prion protein content, indeed during morphine withdrawal a selective unbalance of hippocampal Prion Protein is observable. Moreover, Prion protein overexpression in hippocampal tissue seems to generate a dimeric structure of Prion protein and α-cleavage at the hydrophobic domain. Stress factors or toxic insults can induce cytosolic dimerization of Prion Protein through the hydrophobic domain, which in turn, it stimulates the α-cleavage and the production of neuroprotective Prion protein fragments. We speculate that this might be the mechanism by which stressful stimuli induced by opiate withdrawal and the subsequent long-term homeostatic changes in hippocampal plasticity, modulate the expression and the dynamics of Prion protein.

"Headache Tools to Stay in School": Assessment, Development, and Implementation of an Educational Guide for School Nurses.

BACKGROUND: Headache is the most common type of pain reported in the pediatric population, and chronic headache is an increasingly prevalent and debilitating pain condition in children and adolescents. With large numbers of students experiencing acute headaches and more students with chronic headache reentering typical school settings, greater availability of tailored evidence-based practice guidelines for school nurses is imperative. METHODS: A 2-armed study was developed to assess the need for and evaluate the use and favorability of a headache-driven school nurse guide. Students and their parents were first surveyed on their school nurse's headache knowledge and management skills. School nurses were also interviewed on their desire for a headache educational tool. This feedback aided in developing a headache resource guide. Next, the guide was distributed to school nurses who provided feedback after a 3-month trial. RESULTS: Results indicate that "Headache Tools to Stay in School" is a useful resource in facilitating communication among health care providers, students, families, and school personnel on how to best meet the complex needs of students with headaches. CONCLUSIONS: Given the guide's favorability, we encourage school nurses to demand the creation of additional evidence-based resources. Continued dissemination of this guide may improve students' headache management under the informed care of school nurses, and may encourage the development of more evidence-based guides across various medical conditions.