Benefits and Process of Providing Peer Support for Pediatric Burn Survivors and Caregivers during Inpatient and Outpatient Phases of Recovery.

The World Health Organization reveals that pediatric burns represent a large portion of burns globally (61). Increases in survival rates have guided clinical and research focus on physical, psychological, and social outcomes. Research on other childhood illnesses has shown the efficacy of social support throughout recovery. In the pediatric burn literature, studies have shown the efficacy of burn camps for promoting positive interactions among survivors, learning coping skills, and facilitating socialization and reintegration. However, few studies have focused on the benefits of peer support for pediatric burn survivors and their caregivers in the inpatient and outpatient phases of recovery. This descriptive paper identifies options for building resilience for pediatric burn survivors through peer support in the inpatient and outpatient phases of recovery. The authors discuss options for providing peer support during the coronavirus disease 2019 pandemic on the pediatric intensive care unit, general pediatric floor, and outpatient setting.

Trajectories of physical health-related quality of life among adults living with burn injuries: A burn model system national database investigation to improve early intervention and rehabilitation service delivery.

INTRODUCTION: Understanding trajectories of recovery in key domains can be used to guide patients, families, and caregivers. The purpose of this study was to describe common trajectories of physical health over time and to examine predictors of these trajectories. METHOD: Adults with burn injuries completed self-reported assessments of their health-related quality of life (HRQOL) as measured by the SF-12® Physical Component Summary (PCS) score at distinct time points (preinjury via recall, index hospital discharge, and at 6-, 12-, and 24 months after injury). Growth mixture modeling (GMM) was used to model PCS scores over time. Covariables included burn size, participant characteristics, and scores from the Community Integration Questionnaire (CIQ)/Social Integration portion, Satisfaction With Life Scale (SWLS), and Satisfaction With Appearance Scale (SWAP). RESULTS: Data from 939 participants were used for complete-case analysis. Participants were 72% male, 64% non-Hispanic White, with an average age of 44 years and an average burn size of 20% of total body surface area (TBSA). The best fitting model suggested three distinct trajectories (Class 1 through 3) for HRQOL. We titled each Class according to the characteristics of their trajectory. Class 1 (recovering; n = 632), Class 2 (static; n = 77), and Class 3 (weakened; n = 205) reported near average HRQOL preinjury, then reported lower scores at discharge, with Class 1 subsequently improving to preinjury levels and Class 3 improving but not reaching their preinjury quality of life. Class 3 experienced the largest decrease in HRQOL. Class 2 reported the lowest preinjury HRQOL and remained low for the next 2 years, showing minimal change in their HRQOL. CONCLUSIONS: These findings emphasize the importance of early universal screening and sustained intervention for those most at risk for low HRQOL following injury. For Class 2 (static), lower than average HRQOL before their injury is a warning. For Class 3 (weakened), if the scores at 6 months show a large decline, then the person is at risk for not regaining their HRQOL by 24 months and thus needs all available interventions to optimize their outcomes. Results of this study provide guidance for how to identify people with burn injury who would benefit from more intensive rehabilitation to help them achieve or regain better HRQOL. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

An Examination of Follow-up Services Received by Vulnerable Burn Populations: A Burn Model System National Database Study.

While disparities in healthcare outcomes and services for vulnerable populations have been documented, the extent to which vulnerable burn populations demonstrate disparities in long-term care is relatively underexplored. This study's goal was to assess for differences in long-term occupational or physical therapy (OT/PT) and psychological service use after burn injury in vulnerable populations. Data from the Burn Model System National Database (2006-2015) were analyzed. The vulnerable group included participants in one or more of these categories: 65 years of age or older, nonwhite, no insurance or Medicaid insurance, preinjury receipt of psychological therapy or counseling, preinjury alcohol and/or drug misuse, or with a preexisting disability. Primary outcomes investigated were receipt of OT/PT and psychological services. Secondary outcomes included nine OT/PT subcategories. Outcomes were examined at 6, 12, and 24 months postinjury. One thousand one hundred thirty-six burn survivors (692 vulnerable; 444 nonvulnerable) were included. The vulnerable group was mostly female, unemployed at time of injury, and with smaller burns. Both groups received similar OT/PT and psychological services at all time points. Adjusted regression analyses found that while the groups received similar amounts services, some vulnerable subgroups received significantly more services. Participants 65 years of age or older, who received psychological therapy or counseling prior to injury, and with a preexisting disability received more OT/PT and psychological or peer support services at follow-up. Overall, vulnerable and nonvulnerable groups received comparable OT/PT and psychological services. The importance of long-term care among vulnerable subgroups of the burn population is highlighted by this study. Future work is needed to determine adequate levels of follow-up services.

HDAC3 Regulates the Transition to the Homeostatic Myelinating Schwann Cell State.

The formation of myelinating Schwann cells (mSCs) involves the remarkable biogenic process, which rapidly generates the myelin sheath. Once formed, the mSC transitions to a stable homeostatic state, with loss of this stability associated with neuropathies. The histone deacetylases histone deacetylase 1 (HDAC1) and HDAC2 are required for the myelination transcriptional program. Here, we show a distinct role for HDAC3, in that, while dispensable for the formation of mSCs, it is essential for the stability of the myelin sheath once formed-with loss resulting in progressive severe neuropathy in adulthood. This is associated with the prior failure to downregulate the biogenic program upon entering the homeostatic state leading to hypertrophy and hypermyelination of the mSCs, progressing to the development of severe myelination defects. Our results highlight distinct roles of HDAC1/2 and HDAC3 in controlling the differentiation and homeostatic states of a cell with broad implications for the understanding of this important cell-state transition.

Poverty, population density, and the epidemiology of burns in young children from Mexico treated at a U.S. pediatric burn facility.

INTRODUCTION: Children 5 and younger are at risk for sustaining serious burn injuries. The causes of burns vary depending on demographic, cultural and socioeconomic variables. At this pediatric burn center we provided medical care to children from Mexico with severe injuries. The purpose of this study was to understand the impact of demographic distribution and modifiable risk factors of burns in young children to help guide prevention. METHODS: A retrospective chart review was performed with children 5 and younger from Mexico who were injured from 2000-2013. The medical records of 447 acute patients were reviewed. Frequency counts and percentages were used to identify geographic distribution and calculate incidence of burns. Microsoft Powermap software was used to create a geographical map of Mexico based on types of burns. A binomial logistic regression was used to model the incidence of flame burns as opposed to scald burns in each state with relation to population density and poverty percentage. In all statistical tests, alpha=0.05 for a 95% level of confidence. RESULTS: Burns were primarily caused by flame and scald injuries. Admissions from flame injuries were mainly from explosions of propane tanks and gas lines and house fires. Flame injuries were predominantly from the states of Jalisco, Chihuahua, and Distrito Federal. Scalds were attributed to falling in large containers of hot water or food on the ground, and spills of hot liquids. Scald injuries were largely from the states of Oaxaca, Distrito Federal, and Hidalgo. The odds of a patient having flame burns were significantly associated with poverty percentage (p<0.0001) and population density (p=0.0085). Increasing levels of poverty led to decrease in odds of a flame burn, but an increase in the odds of scald burns. Similarly, we found that increasing population density led to a decrease in the odds of a flame burn, but an increase in the odds of a scald burn. CONCLUSIONS: Burns in young children from Mexico who received medical care at this pediatric burn center were attributed to flame and scalds. Potential demographic associations have been identified. Different states in Mexico have diverse cultural and socioeconomic variables that may influence the etiology of burns in young children and this information may help efficiently tailor burn prevention campaigns for burn prevention efforts in each region. APPLICABILITY OF RESEARCH TO PRACTICE: This information will be used to develop and help modify existing prevention campaigns.

Sorafenib inhibits proliferation and invasion in desmoid-derived cells by targeting Ras/MEK/ERK and PI3K/Akt/mTOR pathways.

Desmoid tumors (DTs) are unusual neoplasms of mesenchymal origin that exhibit locally invasive behavior. Surgical resection is the initial treatment of choice for DTs. For patients with recurrent or unresectable disease, however, medical options are limited. Sorafenib is a multikinase inhibitor with known antitumor activity in various cancers via suppression of the PI3K/Akt/mTOR pathway. Here, we examined the effects of sorafenib on patient-derived DT cell lines, with the aim of characterizing the efficacy and molecular mechanism of action. Early passage DT-derived cells were treated with increasing doses of sorafenib (0-10 µM) and demonstrated up to 90% decrease in proliferation and invasion relative to controls. Signaling arrays identified multiple potential targets of sorafenib in the Ras/MEK/ERK and PI3K/Akt/mTOR signaling cascades. Immunoblot analysis revealed that sorafenib inhibited Akt, MEK and ERK phosphorylation, and this effect correlated with inhibition of total Akt and total MEK, while total ERK levels remained unchanged. Sorafenib also inhibited 4E-BP1 phosphorylation, and this effect correlated with decrease of p-eIF4E and total eIF4E. Finally, in combination with the mammalian target of rapamycin (mTOR) inhibitor everolimus, sorafenib decreased phosphorylation of the ribosomal protein and mTOR effector S6K in an additive manner. Taken together, our results suggest that sorafenib suppresses DT proliferation and invasion via inhibition of Ras/MEK/ERK and PI3K/Akt/mTOR signaling pathways with additional effects on translation. Sorafenib may be a promising therapeutic option in the treatment of DTs. Additional studies in DT patients are warranted to examine the efficacy of combination therapy using sorafenib.

Higher serum vitamin D levels are associated with protective serum cytokine profiles in patients with ulcerative colitis.

BACKGROUND & AIMS: Vitamin D has immune modulating effects on cytokines. Serum vitamin D levels are associated with the risk of relapse in patients with ulcerative colitis (UC), through unknown mechanisms. We tested the hypothesis that this beneficial role of vitamin D on UC is mediated through anti-inflammatory serum cytokine profiles. METHODS: Serum samples from a prospective cohort of seventy UC patients in clinical remission were collected and baseline histological and endoscopic scores were recorded at enrollment. Clinical relapse events were recorded over the 12-month follow-up period. Serum vitamin D and cytokines levels (IL-6, IL-8, IL-17A, TNF-α, IFN-γ, IL-4, IL-10) were quantified using ELISA. Linear regression was used to determine correlation between vitamin D and cytokine profiles. Logistic regression models were used to determine the association between serum cytokine profiles and baseline histologic mucosal healing and clinical relapse. RESULTS: Higher serum vitamin D levels positively correlated with higher ratios of IL-4 + IL-10/IL-17A + TNF-α (r = 0.37, P < .01), and IL-4 + IL-10/IL-6 + TNF-α (r = 0.32, P < .01). In multivariate analysis, IL-4 + IL-10/IL-17A + TNF-α ratios at baseline were associated with the presence of histologic mucosal healing (O.R. 1.29, 95% CI 1.02-1.62, P = .03). A higher ratio of serum IL-4 + IL-10 to IL-6 + TNF-α was associated with a reduced risk of clinical relapse (O.R. 0.72, 95% CI 0.58-0.89, P = .003), and longer time to relapse (p = .03), over the 12-month follow-up period. This ratio during remission had an AUC of 0.7 in predicting later clinical relapse. CONCLUSIONS: Vitamin D is associated with anti-inflammatory serum cytokine profiles. Anti-inflammatory cytokine patterns may mediate the protective effects of higher serum vitamin D levels in patients with ulcerative colitis.

Use of gabapentin and pregabalin for pruritus and neuropathic pain associated with major burn injury: A retrospective chart review.

INTRODUCTION: Pruritis after burn is one of the most common chronic complaints in burn survivors. Pruritus is often indistinguishable from neuropathic pain. There is a paucity of studies reporting the use of gabapentin and pregabalin to treat both pruritus and neuropathic pain. The purpose of this current study is to explore and document the effect of gabapentin and pregabalin in children and adolescent burn survivors. METHODS: A retrospective review of charts and pharmacy records of gabapentin and pregabalin dispensed to control pruritus and/or pain was conducted for burn survivors up to 20 years of age. Data collected included medication doses, age and weight of patients, presence of neuropathic pain and pruritus, reported response to medication, and side effects of these medications. 136 individuals who received gabapentin, pregabalin, or both medications are included in the study. 112 received only gabapentin, none received only pregabalin, and 24 received both. All results are documented in mean±standard deviation (s.d.) dose/kg/day. 104 individuals experienced pruritus exclusively, two experienced neuropathic pain exclusively, and 30 experienced both. Use of medications was considered effective if the individuals reported pruritus or pain relief from the medication. The medication was considered safe if the individuals did not experience adverse side effects warranting discontinuation of the drugs. Medications were continued with dose adjustments if an individual reported minor side effects such as sedation or hyperactivity. RESULTS: The average effective dose mg/kg/day for gabapentin and pregabalin was calculated for each of the three age groups (≤5years, 6-12 years, and >12years). The average effective dose of gabapentin was 23.9±10.3mg/kg/day for children ≤5years, 27.0±15.3mg/kg/day for children 6-12 years, and 34.1±15.7mg/kg/day for children >12years. The average effective dose of pregabalin was 6.5±3.5mg/kg/day for children 6-12 years and 4.7±1.6mg/kg/day for children >12years. One 5-year-old child received 3.7mg/kg/day of pregabalin. Note that for all patients in this study, pregabalin was added after an inadequate response to gabapentin. For individuals receiving both gabapentin and pregabalin, the maximum gabapentin failure dose for pruritus was 32.8±18.0mg/kg/day and for both pain and pruritus was 28.1±18.3mg/kg/day. For individuals treated with only gabapentin, 91.4% had an adequate response for pruritus, 100% for neuropathic pain, and 43.3% for both pruritus and pain. 100% of individuals treated with both gabapentin and pregabalin had an adequate response for pruritus and 88.2% had an adequate response for both pruritus and pain. Gabapentin was associated with hyperactivity in two individuals, and sedation in one individual. One individual reported nausea, vomiting, and headaches when taking both medications; this resolved when gabapentin was discontinued. One individual reported sedation while taking both medications. CONCLUSION: Gabapentin and pregabalin are effective in relieving pruritus and neuropathic pain in most burn survivors. In some instances, these medications can be given together. Few individuals reported side effects.

Does Acute Propranolol Treatment Prevent Posttraumatic Stress Disorder, Anxiety, and Depression in Children with Burns?

OBJECTIVE: This study examined whether acute propranolol treatment prevented posttraumatic stress disorder (PTSD), anxiety, and depression in children hospitalized in the pediatric intensive care unit for large burns. We hypothesized that the prevalence of PTSD, anxiety, and depression would be significantly less in the propranolol than nonpropranolol groups. METHODS: Children who had previously participated in a randomized controlled clinical trial of acute propranolol and nonpropranolol controls were invited to participate in long-term follow-up interviews. Eligible participants from 1997 to 2008 were identified from the electronic medical records, and data were collected in 2010-2011. Measures included the Missouri Assessment of Genetics Interview for Children to assess lifetime PTSD, Revised Children's Manifest Anxiety Scale to assess anxiety, and two depression inventories Children's Depression Inventory and Beck Depression Inventory-II. RESULTS: Of 202 participants, 89 were in the propranolol group and 113 were nonpropranolol controls. Children were an average of 7 years postburn. The average total body surface area burned was 56.4 + 15.1% (range = 24%-99%). The mean dose of propranolol was 3.64 ± 3.19 mg/kg per day (range = 0.36-12.12). The duration of propranolol inpatient treatment days varied, mean days 26.5 ± 19.8. The prevalence of lifetime PTSD in the propranolol group was 3.5% and controls 7.2%, but this difference was not statistically significant. We controlled for administration of pain medications, anxiolytics, and antidepressants overall and no significant differences were detected in the rates of PTSD, anxiety, or depression. CONCLUSIONS: The prevalence of PTSD, anxiety, and depression was similar in children who received propranolol acutely and those who did not. This may be influenced by the standard of care that all children received timely pharmacotherapy for pain and anxiety management and psychotherapy beginning in their acute phase of treatment.

The Use of Virtual Reality Facilitates Dialectical Behavior Therapy® "Observing Sounds and Visuals" Mindfulness Skills Training Exercises for a Latino Patient with Severe Burns: A Case Study.

Sustaining a burn injury increases an individual's risk of developing psychological problems such as generalized anxiety, negative emotions, depression, acute stress disorder, or post-traumatic stress disorder. Despite the growing use of Dialectical Behavioral Therapy® (DBT®) by clinical psychologists, to date, there are no published studies using standard DBT® or DBT® skills learning for severe burn patients. The current study explored the feasibility and clinical potential of using Immersive Virtual Reality (VR) enhanced DBT® mindfulness skills training to reduce negative emotions and increase positive emotions of a patient with severe burn injuries. The participant was a hospitalized (in house) 21-year-old Spanish speaking Latino male patient being treated for a large (>35% TBSA) severe flame burn injury. Methods: The patient looked into a pair of Oculus Rift DK2 virtual reality goggles to perceive the computer-generated virtual reality illusion of floating down a river, with rocks, boulders, trees, mountains, and clouds, while listening to DBT® mindfulness training audios during 4 VR sessions over a 1 month period. Study measures were administered before and after each VR session. Results: As predicted, the patient reported increased positive emotions and decreased negative emotions. The patient also accepted the VR mindfulness treatment technique. He reported the sessions helped him become more comfortable with his emotions and he wanted to keep using mindfulness after returning home. Conclusions: Dialectical Behavioral Therapy is an empirically validated treatment approach that has proved effective with non-burn patient populations for treating many of the psychological problems experienced by severe burn patients. The current case study explored for the first time, the use of immersive virtual reality enhanced DBT® mindfulness skills training with a burn patient. The patient reported reductions in negative emotions and increases in positive emotions, after VR DBT® mindfulness skills training. Immersive Virtual Reality is becoming widely available to mainstream consumers, and thus has the potential to make this treatment available to a much wider number of patient populations, including severe burn patients. Additional development, and controlled studies are needed.

Low Serum Vitamin D During Remission Increases Risk of Clinical Relapse in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Vitamin D levels have been associated with disease activity in patients with ulcerative colitis (UC), but it is unclear whether they affect the risk of disease relapse. We sought to determine the association between baseline vitamin D levels during a period of clinical remission and risk of subsequent UC relapse. METHODS: We performed a physician-blinded prospective study of 70 patients with UC in clinical remission followed up after a surveillance colonoscopy at a tertiary academic medical center. Serum samples were collected at the time of colonoscopy and baseline endoscopic and histologic activity were determined. Levels of 25-hydroxy-vitamin D were measured using an enzyme-linked immunosorbent assay. The primary outcome was rate of clinical relapse, determined over 12 months. RESULTS: The mean baseline vitamin D level was lower among patients with relapse (29.5 ng/mL) than without (50.3 ng/mL) (P = .001). Remission vitamin D level (≤35 ng/mL) was associated with a risk of clinical relapse (odds ratio, 1.25; 95% confidence interval [CI], 1.01-1.56; P = .044) over 12 months, independent of endoscopic or histologic grade at enrollment. A receiver operating characteristic curve of vitamin D levels for the outcome of relapse had an area under the curve of 0.72; and a serum level of 35 ng/mL or less had a sensitivity of 70% (95% CI, 46%-88%) and a specificity of 74% (95% CI 57%-83%) for predicting risk of clinical relapse. CONCLUSIONS: Serum levels of vitamin D of 35 ng/mL or less during periods of clinical remission increase the risk of UC relapse. Clinical trials to obtain vitamin D levels higher than this threshold should be considered.

The epidemiology of burns in young children from Mexico treated at a U.S. hospital.

INTRODUCTION: Young children are the most vulnerable for sustaining burns. At this pediatric burn hospital we have provided medical care to young children with severe burns from Mexico for many years. This study identified modifiable risk factors that could be used to assist in prevention of burns in this age group. METHODS: A retrospective chart review was performed with children <5 years of age from Mexico who were injured from 2000 to 2013. The medical records of 447 acute patients were reviewed. RESULTS: There were 187 females and 260 males with large burns >20% total body surface area (TBSA) burned. Primary causes of burns were flame and scalds. Children with flame injuries were older (3.0±1.5 years of age) than those with scalds (2.6±1.2 years of age). Admissions attributed to flame burns were largely from explosions by propane tanks, gas line leaks, and house fires. Most admissions for scalds were predominantly from falling in large containers of hot water, food, or grease; and fewer were attributed to spills from hot liquids. Most cases reported to a social service agency were to find resources for families. Mortality rate for flame and scald burns was low. CONCLUSIONS: It is important take into account demographic, cultural, and socioeconomic variables when developing and implementing prevention programs. Burn prevention instruction for parents is crucial.

Design of a small molecule against an oncogenic noncoding RNA.

The design of precision, preclinical therapeutics from sequence is difficult, but advances in this area, particularly those focused on rational design, could quickly transform the sequence of disease-causing gene products into lead modalities. Herein, we describe the use of Inforna, a computational approach that enables the rational design of small molecules targeting RNA to quickly provide a potent modulator of oncogenic microRNA-96 (miR-96). We mined the secondary structure of primary microRNA-96 (pri-miR-96) hairpin precursor against a database of RNA motif-small molecule interactions, which identified modules that bound RNA motifs nearby and in the Drosha processing site. Precise linking of these modules together provided Targaprimir-96 (3), which selectively modulates miR-96 production in cancer cells and triggers apoptosis. Importantly, the compound is ineffective on healthy breast cells, and exogenous overexpression of pri-miR-96 reduced compound potency in breast cancer cells. Chemical Cross-Linking and Isolation by Pull-Down (Chem-CLIP), a small-molecule RNA target validation approach, shows that 3 directly engages pri-miR-96 in breast cancer cells. In vivo, 3 has a favorable pharmacokinetic profile and decreases tumor burden in a mouse model of triple-negative breast cancer. Thus, rational design can quickly produce precision, in vivo bioactive lead small molecules against hard-to-treat cancers by targeting oncogenic noncoding RNAs, advancing a disease-to-gene-to-drug paradigm.

Histology Grade Is Independently Associated With Relapse Risk in Patients With Ulcerative Colitis in Clinical Remission: A Prospective Study.

OBJECTIVES: Objective evidence of inflammation has been associated with the risk of relapse in patients with ulcerative colitis (UC) who are in clinical remission. We compared endoscopic and histologic grades for their ability to predict clinical relapse in this patient population. METHODS: Patients with UC in clinical remission were prospectively enrolled into an observational cohort. Baseline endoscopic scores (Mayo) and histological (Geboes) grades and blood markers were collected. All subjects were followed for 12 months and relapse determined using clinical indices. RESULTS: A total of 179 subjects were enrolled into the study and followed for 12 months. Clinical relapse occurred in 23%; 5% were hospitalized, and 2% underwent colectomy. In univariate analysis, the baseline Mayo endoscopy score and the Geboes histology grade were significantly associated with the later development of clinical relapse (P<0.001 for both), but only the histology grade remained significant in a multivariate model (P=0.006). The relative risk of clinical relapse was 3.5 (95% CI 1.9-6.4, P<0.0001) in subjects whose baseline Geboes grade was ≥3.1. The area under the curve was 0.73 for the Geboes histology grade to identify subjects at risk of future clinical relapse. Of the patients in clinical, endoscopic, and histological remission at baseline (n=82), only 7% had a clinical relapse over the subsequent 12 months. CONCLUSIONS: Histology grade has the strongest association with the risk of clinical relapse in patients with UC who are in clinical remission. Consideration should be given to including this end point in evaluating therapy for UC.

Therapeutic targeting of casein kinase 1δ in breast cancer.

Identification of specific drivers of human cancer is required to instruct the development of targeted therapeutics. We demonstrate that CSNK1D is amplified and/or overexpressed in human breast tumors and that casein kinase 1δ (CK1δ) is a vulnerability of human breast cancer subtypes overexpressing this kinase. Specifically, selective knockdown of CK1δ, or treatment with a highly selective and potent CK1δ inhibitor, triggers apoptosis of CK1δ-expressing breast tumor cells ex vivo, tumor regression in orthotopic models of triple-negative breast cancer, including patient-derived xenografts, and tumor growth inhibition in human epidermal growth factor receptor 2-positive (HER2(+)) breast cancer models. We also show that Wnt/ß-catenin signaling is a hallmark of human tumors overexpressing CK1δ, that disabling CK1δ blocks nuclear accumulation of ß-catenin and T cell factor transcriptional activity, and that constitutively active ß-catenin overrides the effects of inhibition or silencing of CK1δ. Thus, CK1δ inhibition represents a promising strategy for targeted treatment in human breast cancer with Wnt/ß-catenin involvement.

Does acute stress disorder predict subsequent posttraumatic stress disorder in pediatric burn survivors?

OBJECTIVE: This study examined the prevalence of posttraumatic stress disorder (PTSD) in pediatric burn survivors who had been treated for acute stress disorder (ASD) symptoms during their initial hospitalization and compared them to patients who had been asymptomatic for ASD symptoms. METHOD: Participants were identified from electronic medical records from 1995 to 2008 and data were collected from 2006 to 2008. Participants were primarily matched on total body surface area burned and gender, and as close as possible on age at time of burn and number of years postburn. Pediatric burn survivors completed a semistructured clinical interview, the Missouri Assessment of Genetics Interview for Children-PTSD section, which is based on criteria from the DSM-IV for evaluating lifetime PTSD. RESULTS: There were 183 participants in the study, and from this sample 85 matched pairs were identified. Most were 5 years postburn. The prevalence of PTSD at the time of follow-up was 8.24% (7 of 85) for the ASD group and 4.71% (4 of 85) for the non-ASD comparison group. No significant differences were found between these groups at P value ≥ .05. A logistic regression analysis was conducted to determine if prior ASD diagnosis, burn size, gender, ethnicity, age at time of study participation, and number of years postburn predicted subsequent PTSD. None of the variables were significant predictors. CONCLUSION: The prevalence of PTSD was similar in children who had ASD symptoms and those without ASD symptoms. The lifetime prevalence of PTSD was lower than reported in other studies. A possible explanation for this finding is that children received timely pharmacotherapy and psychotherapy during their acute hospitalization.

Identification of an EGFRvIII-JNK2-HGF/c-Met-Signaling Axis Required for Intercellular Crosstalk and Glioblastoma Multiforme Cell Invasion.

Glioblastoma multiforme (GBM) is the most aggressive and common form of adult brain cancer. Current therapeutic strategies include surgical resection, followed by radiotherapy and chemotherapy. Despite such aggressive multimodal therapy, prognosis remains poor, with a median patient survival of 14 months. A proper understanding of the molecular drivers responsible for GBM progression are therefore necessary to instruct the development of novel targeted agents and enable the design of effective treatment strategies. Activation of the c-Jun N-terminal kinase isoform 2 (JNK2) is reported in primary brain cancers, where it associates with the histologic grade and amplification of the epidermal growth factor receptor (EGFR). In this manuscript, we demonstrate an important role for JNK2 in the tumor promoting an invasive capacity of EGFR variant III, a constitutively active mutant form of the receptor commonly found in GBM. Expression of EGFR variant III induces transactivation of JNK2 in GBM cells, which is required for a tumorigenic phenotype in vivo. Furthermore, JNK2 expression and activity is required to promote increased cellular invasion through stimulation of a hepatocyte growth factor-c-Met signaling circuit, whereby secretion of this extracellular ligand activates the receptor tyrosine kinase in both a cell autonomous and nonautonomous manner. Collectively, these findings demonstrate the cooperative and parallel activation of multiple RTKs in GBM and suggest that the development of selective JNK2 inhibitors could be therapeutically beneficial either as single agents or in combination with inhibitors of EGFR and/or c-Met.

Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves.

The peripheral nervous system has remarkable regenerative capacities in that it can repair a fully cut nerve. This requires Schwann cells to migrate collectively to guide regrowing axons across a 'bridge' of new tissue, which forms to reconnect a severed nerve. Here we show that blood vessels direct the migrating cords of Schwann cells. This multicellular process is initiated by hypoxia, selectively sensed by macrophages within the bridge, which via VEGF-A secretion induce a polarized vasculature that relieves the hypoxia. Schwann cells then use the blood vessels as "tracks" to cross the bridge taking regrowing axons with them. Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair. This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue.

Immediate and long-term psychological problems for survivors of severe pediatric electrical injury.

OBJECTIVE: To compare psychological difficulties experienced during the initial acute hospitalization and the last follow up visit for children with electrical injuries (EI) and children without electrical injuries (non-EI). We hypothesized that children with electrical burns would have different psychological outcomes. METHODS: This retrospective study compared emotional and cognitive functioning of EI patients and a matched group of survivors of other burns. RESULTS: Medical records of 67 patients with and without EI were reviewed. For the EI group, the mean age at injury was 12.6±3.9 years, the mean age at follow up was 15.5±4.6 years, and mean TBSA 32±21%. For the Non-EI group, the mean age at injury was 12.4±3.9 years, the mean age at follow up was 14.5±4.7 years, and mean TBSA 32±21.5%. During the acute hospitalization, a significant difference was found between the groups in the area of neuropathic pain (Chi-square tests p<0.011). Individuals with EI were more likely to have acute stress disorder/post-traumatic stress disorder as well as amnesia of the accident than the controls; however, this did not reach statistical significance. No differences were found between the groups in other psychological areas. Follow up information from the last documented psychology/psychiatric visit revealed an equal number of patients experienced anxiety disorders, depression, grief, behavioral problems, and cognitive difficulties. CONCLUSIONS: Some differences were evident between the groups immediately after injury; however, long term outcomes were similar.