Infant With Acute Bilateral Pneumothorax During Air Transport.

In rural settings, medically complicated patients may require air transport to facilities that are capable of providing higher levels of care. Extra consideration must be given to pulmonary pathologies when considering this mode of transport. Altitude changes impact both air pressure and volume as described by Boyle's law. These changes can complicate the care of these patients in several ways. We present a case of patient with respiratory failure secondary to viral infection who developed acute bilateral pneumothorax (PTX) while mechanically ventilated during a transport on a fixed-wing aircraft. In this article we outline the unique risks of air travel on the development and progression of PTX as well as the unique challenges with diagnosis and treatment during air transport.

Intracranial Hemorrhage Secondary to Vitamin K Deficiency Bleeding in a Newborn.

We present a case of a 6-week-old infant who presented with seizure-like activity. Workup revealed abnormal coagulation and imaging confirmed intracranial hemorrhage. Parental refusal of vitamin K treatment at birth suggested vitamin K deficiency bleeding (VKDB) in this newborn. Though VKDB is rare in developed countries, rates have been rising which coincides with an increasing trend of parental refusal of vitamin K prophylaxis at birth.

Impact of Payer Status on Hospitalization Outcomes in Pediatric Diabetic Ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening complication seen in patients suffering from type I diabetes (T1D) with a cost burden of over $5 billion in the U.S. annually. Often, children are first diagnosed with T1D when they present with DKA. Our study examines the impact of payer type on pediatric DKA. We hypothesize that Medicaid payer type negatively impacts costs and care outcomes in pediatric patients with DKA as compared to private payers. METHODS: We utilized the Agency for Healthcare Research and Quality (AHRQ) 2012 Kids' Inpatient Database (KID) for analysis. Our inclusion criterion included All Patient Refined Diagnosis Related Groups (APR-DRG) coding for T1D DKA admissions with a uniform severity and an identifiable payer of Medicaid or private insurance. RESULTS: 27,241 weighted and severity-adjusted discharges met criterion (51.6 percent Medicaid payers, 48.4 percent private). Comparing Medicaid vs. private payer status, we found: length of stay (2.24 days vs. 2.09), number of procedures received (0.13 vs. 0.12), and total charges ($16,449 vs. $16,107). Limiting analysis to a crude measure of bottom quartile income showed: length of stay (2.26 days vs. 2.14), number of procedures received (0.12 vs. 0.12), and total charges ($15,393 vs. $14,063). CONCLUSIONS: Children admitted in DKA and covered by Medicaid had longer hospitalizations, more procedures performed, and higher total costs of care. Even after controlling for socioeconomic status, similar effects persisted. Further evaluations are warranted to reveal the causative factors behind these correlative findings which suggest DKA patients receive different care depending on their payer status.

Orexin/hypocretin receptor modulation of anxiolytic and antidepressive responses during social stress and decision-making: Potential for therapy.

Hypothalmic orexin/hypocretin (Orx) neurons in the lateral and dorsomedial perifornical region (LH-DMH/PeF) innervate broadly throughout the brain, and receive similar inputs. This wide distribution, as well as two Orx peptides (OrxA and OrxB) and two Orx receptors (Orx1 and Orx2) allow for functionally related but distinctive behavioral outcomes, that include arousal, sleep-wake regulation, food seeking, metabolism, feeding, reward, addiction, and learning. These are all motivational functions, and tie the orexin systems to anxiety and depression as well. We present evidence, that for affective behavior, Orx1 and Orx2 receptors appear to have opposing functions. The majority of research on anxiety- and depression-related outcomes has focused on Orx1 receptors, which appear to have primarily anxiogenic and pro-depressive actions. Although there is significant research suggesting contrary findings, the primary potential for pharmacotherapies linked to the Orx1 receptor is via antagonists to block anxious and depressive behavior. Dual orexin receptor antagonists have been approved for treatment of sleep disorders, and are likely candidates for adaptation for affect disorder treatments. However, we present evidence here that demonstrates the Orx2 receptors are anxiolytic and antidepressive. Using a new experimental pre-clinical model of anxious and depressive behavior stimulated by social stress and decision-making that produces two stable behavioral phenotypes, Escape/Resilient and Stay/Susceptible, we tested the effects of intracerebroventricular injections of Orx2 agonist and antagonist drugs. Over ten behavioral measures, we have demonstrated that Orx2 agonists promote resilience, as well as anxiolytic and antidepressive behavior. In contrast, Orx2 antagonists or knockdown kindle anxious and pro-depressive behavior plus increase susceptibility. The results suggest that the Orx2 receptor may be a useful target for pharmacotherapies to treat anxiety and depression.

Learning and CRF-Induced Indecision during Escape and Submission in Rainbow Trout during Socially Aggressive Interactions in the Stress-Alternatives Model.

Socially stressful environments induce a phenotypic dichotomy of coping measures for populations in response to a dominant aggressor and given a route of egress. This submission- (Stay) or escape-oriented (Escape) dichotomy represents individual decision-making under the stressful influence of hostile social environments. We utilized the Stress-Alternatives Model (SAM) to explore behavioral factors which might predict behavioral phenotype in rainbow trout. The SAM is a compartmentalized tank, with smaller and larger trout separated by an opaque divider until social interaction, and another divider occluding a safety zone, accessible by way of an escape route only large enough for the smaller fish. We hypothesized that distinctive behavioral responses during the first social interaction would indicate a predisposition for one of the behavioral phenotypes in the subsequent interactions. Surprisingly, increased amount or intensity of aggression received had no significant effect on promoting escape in test fish. In fact, during the first day of interaction, fish that turned toward their larger opponent during attack eventually learned to escape. Escaping fish also learn to monitor the patrolling behavior of aggressors, and eventually escape primarily when they are not being observed. Escape per se, was also predicted in trout exhibiting increased movements directed toward the escape route. By contrast, fish that consistently remained in the tank with the aggressor (Stay) showed significantly higher frequency of swimming in subordinate positions, at the top or the bottom of the water column, as well as sitting at the bottom. In addition, a corticotropin-releasing factor (CRF)-induced behavior, snap-shake, was also displayed in untreated fish during aggressive social interaction, and blocked by a CRF1 receptor antagonist. Especially prevalent among the Stay phenotype, snap-shake indicates indecision regarding escape-related behaviors. Snap-shake was also exhibited by fish of the Escape phenotype, showing a positive correlation with latency to escape. These results demonstrate adaptive responses to stress that reflect evolutionarily conserved stress neurocircuitry which may translate to psychological disorders and decision-making across vertebrate taxa.

Nuance and behavioral cogency: How the Visible Burrow System inspired the Stress-Alternatives Model and conceptualization of the continuum of anxiety.

By creating the Visible Burrow System (VBS) Bob Blanchard found a way to study the interaction of genetics, physiology, environment, and adaptive significance in a model with broad validity. The VBS changed the way we think about anxiety and affective disorders by allowing the mechanisms which control them to be observed in a dynamic setting. Critically, Blanchard used the VBS and other models to show how behavioral systems like defense are dependent upon context and behavioral elements unique to the individual. Inspired by the VBS, we developed a Stress Alternatives Model (SAM) to further explore the multifaceted dynamics of the stress response with a dichotomous choice condition. Like the VBS, the SAM is a naturalistic model built upon risk assessment and defensive behavior, but with a choice of response: escape or submission to a large conspecific aggressor. The anxiety of novelty during the first escape must be weighed against fear of the aggressor, and a decision must be made. Both outcomes are adaptively significant, evidenced by a 50/50 split in outcome across several study systems. By manipulating the variables of the SAM, we show that a gradient of anxiety exists that spans the contextual settings of escaping an open field, escaping from aggression, and submitting to aggression. These findings correspond with increasing levels of corticosterone and increasing levels of NPS and BDNF in the central amygdala as the context changes.Whereas some anxiolytics were able to reduce the latency to escape for some animals, only with the potent anxiolytic drug antalarmin (CRF1R-blocker) and the anxiogenic drug yohimbine (α2 antagonist) were we able to reverse the outcome for a substantial proportion of individuals. Our findings promote a novel method for modeling anxiety, offering a distinction between low-and-high levels, and accounting for individual variability. The translational value of the VBS is immeasurable, and it guided us and many other researchers to seek potential clinical solutions through a deeper understanding of regional neurochemistry and gene expression in concert with an ecological behavioral model.

Anxiolytic function of the orexin 2/hypocretin A receptor in the basolateral amygdala.

The orexin/hypocretin system interacts with many of the same circuitries contributing to stress-associated disorders like depression and anxiety. These include potentially reciprocal connections with corticotropin releasing factor (CRF) neurons which drive the hypothalamic-pituitary-adrenal (HPA) endocrine response in addition to having an anxiogenic effect in the central amygdala (CeA). Antagonism of the orexin type 1 receptor (Orx1) in the hypothalamus has also been shown to block panic attacks. However, few studies have investigated the effect of orexinergic signaling in the basolateral amygdala (BLA) which is responsible for contextual fear, and modulates the activity of the CeA. To this end, we chronically stressed c57bl/6 mice with social defeat and examined the gene expression of the orexin receptors in the BLA. We found that the transcripts for the Orx1 and Orx2 receptors diverged in the BLA with Orx1 increasing and Orx2 decreasing in animals that were susceptible to the chronic defeat. These changes were not seen in the prelimbic cortex (PrL) which sends efferents to the BLA. We then tried to recapitulate these expression patterns in the BLA using short hairpin interfering sequences delivered by adeno-associated viruses to knock down the orexin receptors. While the Orx1 knockdown did reduce locomotor activity, it did not decrease depressive or anxious behaviors. Knocking down the Orx2 receptors in the BLA increased anxious behavior as measured by reduced social preference and reduced time spent in the center of an open field. Due to the divergent expression patterns of the two receptors in response to chronic stress, orexinergic activity in the BLA may be responsible for bidirectional modulation of anxious behavior. Furthermore, these data raise the possibility that an Orx2 agonist may serve as an effective means to treat anxiety disorders.

Depressive behavior and activation of the orexin/hypocretin system.

The orexin/hypocretin peptide signaling system plays a neuromodulatory role in motivation and stress; two critical components of depression. Although work has been done to identify links between orexin and depression, few specific neuroanatomical associations have been made. These studies have not investigated the relationship between orexin and orexin receptor expression in specific brain regions associated with this disorder. To address this, we examined immobility during the forced swim test (FST) in mice, a commonly used measure of depressive behavior. We analyzed the variation in FST immobility with the distribution of orexin and its receptor mRNA. We found that animals that exhibited more robust depressive behavior had greater or lesser orexin system expression that depended on the limbic brain region analyzed. In the hippocampus there was a negative correlation between orexin expression and FST immobility. Animals that displayed relatively more depressive behavior had lower hippocampal expression of Orexin A (OrxA). In the amygdala, there was a curvilinear relationship between OrxA and FST performance. In addition there was a positive correlation with amygdalar Type I orexin receptor (Orx1) mRNA and depressive behavior. Despite the differences in limbic orexin expression, there was no correlation between immobility and hypothalamic orexin neuron activation as measured by c-Fos. Overall, more severe depressive behavior was associated with reduced hippocampal orexin expression, contrasted with increased orexin plus Orx1 receptor mRNA expression in the amygdala. This divergent pattern between the hippocampus and amygdala mirrors a neurobiological theme seen in depression resulting from reduced hippocampal, but increased amygdalar, size and function.

Contrasting hippocampal and amygdalar expression of genes related to neural plasticity during escape from social aggression.

Social subjugation has widespread consequences affecting behavior and underlying neural systems. We hypothesized that individual differences in stress responsiveness were associated with differential expression of neurotrophin associated genes within the hippocampus and amygdala. To do this we examined the brains of hamsters placed in resident/intruder interactions, modified by the opportunity to escape from aggression. In the amygdala, aggressive social interaction stimulated increased BDNF receptor TrK(B) mRNA levels regardless of the ability to escape the aggressor. In contrast, the availability of escape limited the elevation of GluR(1) AMPA subunit mRNA. In the hippocampal CA(1), the glucocorticoid stress hormone, cortisol, was negatively correlated with BDNF and TrK(B) gene expression, but showed a positive correlation with BDNF expression in the DG. Latency to escape the aggressor was also negatively correlated with CA(1) BDNF expression. In contrast, the relationship between amygdalar TrK(B) and GluR(1) was positive with respect to escape latency. These results suggest that an interplay of stress and neurotrophic systems influences learned escape behavior. Animals which escape faster seem to have a more robust neurotrophic profile in the hippocampus, with the opposite of this pattern in the amygdala. We propose that changes in the equilibrium of hippocampal and amygdalar learning result in differing behavioral stress coping choices.