A novel, reverse-phase-shifting, thermoreversible foaming hydrogel containing antibiotics for the treatment of thermal burns in a swine model - A pilot study.

BACKGROUND: This study compared a novel topical hydrogel burn dressing (CI-PRJ012) to standard of care (silver sulfadiazine) and to untreated control in a swine thermal burn model, to assess for wound healing properties both in the presence and absence of concomitant bacterial inoculation. METHODS: Eight equal burn wounds were created on six Yorkshire swine. Half the wounds were randomized to post-burn bacterial inoculation. Wounds were subsequently randomized to three treatments groups: no intervention, CI-PRJ012, or silver sulfadiazine cream. At study end, a blinded pathologist evaluated wounds for necrosis and bacterial colonization. RESULTS: When comparing CI-PRJ012 and silver sulfadiazine cream to no treatment, both agents significantly reduced the amount of necrosis and bacteria at 7 days after wound creation (p < 0.01, independently for both). Further, CI-PRJ012 was found to be significantly better than silver sulfadiazine (p < 0.02) in reducing bacterial colonization. For wound necrosis, no significant difference was found between silver sulfadiazine cream and CI-PRJ012 (p = 0.33). CONCLUSIONS: CI-PRJ012 decreases necrosis and bacterial colonization compared to no treatment in a swine model. CI-PRJ012 appeared to perform comparably to silver sulfadiazine. CI-PRJ012, which is easily removed with the application of room-temperature water, may provide clinical advantages over silver sulfadiazine.

Neural correlates of inhibitory control in the context of infant cry and paternal postpartum mental health.

BACKGROUND: Inhibitory control, a form of self-regulation, may support sensitive parenting, but has been understudied in new fathers despite their pronounced risk for stress and mental health challenges. METHODS: This study probed the neural correlates of inhibitory control and its associations to first-time fathers' postpartum mental health, focusing on depressive symptoms, state anxiety, and perceived stress. Six months after their child's birth, 38 fathers self-reported on their mood, anxiety, and stress, and performed a Go/No-Go fMRI task while listening to three sets of sounds (infant cry, pink noise, and silence). RESULTS: Fathers' behavioral inhibition accuracy was consistent across the sound conditions, but their patterns of neural activation varied. Compared to the pink noise condition, fathers showed heightened engagement in prefrontal regulatory regions when self-regulating during the infant cry and silent conditions. When examining correct trials only, results in visual motor area and primary somatosensory cortex emerged only for infant cry and not for pink noise and silence. Moreover, fathers reporting higher levels of postpartum depression, state anxiety, and perceived stress showed greater activation in prefrontal regions when inhibiting during infant cry or silence. CONCLUSION: This study is the first to underscore the complex interplay between the neural mechanisms related to inhibitory control and postpartum mental health and stress across varied auditory context, laying the groundwork for future research.

Thermoreversible Reverse-Phase-Shift Foam for Treatment of Noncompressible Torso Hemorrhage, a Safety Trial in a Porcine Model.

INTRODUCTION: Noncompressible torso hemorrhage is the leading cause of exsanguination on the battlefield. A self-expanding, intraperitoneal deployed, thermoreversible foam has been developed that can be easily administered by a medic in austere settings to temporarily tamponade noncompressible torso hemorrhage. The purpose of this study was to assess the long-term safety and physical characteristics of using Fast Onset Abdominal Management (FOAM; Critical Innovations LLC) in swine. MATERIALS AND METHODS: Yorkshire swine (40-60 kg) were sedated, intubated, and placed on ventilatory support. An external jugular catheter was placed for sampling of blood. Continuous heart rate, temperature, saturation of peripheral oxygen, end-tidal carbon dioxide, and peak airway pressures were monitored for a 4-hour period after intervention (i.e., FOAM agent injection or a sham introducer without agent delivery). The FOAM agent was injected to obtain an intra-abdominal pressure of 60 mmHg for at least 10 minutes. After 4 hours, the animals were removed from ventilatory support and returned to their housing for a period of 7-14 days. Group size analysis was not performed, as this was a descriptive safety study. Blood samples were obtained at baseline and at 1-hour post-intervention and then on days 1, 3, 7, and 14. Euthanasia, necropsy, and harvesting of samples for histologic analysis (from kidneys, terminal ilium, liver, pancreas, stomach, spleen, and lungs) were performed upon expiration. Histologic scoring for evidence of ischemia, necrosis, and abdominal compartment sequela was blinded and reported by semi-quantitative scale (range 0-4; 0 = no change, 1 = minimal, 2 = mild, 3 = moderate, and 4 = marked). Oregon Health & Science University's Institutional Animal Care and Use Committee, as well as the U.S. Army Animal Care and Use Review Office, approved this protocol before the initiation of experiments (respectively, protocol numbers IP00003591 and MT180006.e002). RESULTS: Five animals met a priori inclusion criteria, and all of these survived to their scheduled endpoints. Two animals received sham injections of the FOAM agent (one euthanized on day 7 and one on day 14), and three animals received FOAM agent injections (one euthanized on day 7 and two on day 14). A transitory increase in creatinine and lactate was detected during the first day in the FOAM injected swine but resolved by day 3. No FOAM agent was observed in the peritoneal cavity upon necropsy at day 7 or 14. Histologic data revealed no clinically relevant differences in any organ system between intervention and control animals upon sacrifice at day 7 or 14. CONCLUSIONS: This study describes the characteristics, survival, and histological analysis of using FOAM in a porcine model. In our study, FOAM reached the desired intra-abdominal pressure endpoint while not significantly altering basic hematologic parameters, except for transient elevations of creatinine and lactate on day 1. Furthermore, there was no clinical or histological relevant evidence of ischemia, necrosis, or intra-abdominal compartment syndrome. These results provide strong support for the safety of the FOAM device and will support the design of further regulatory studies in swine and humans.

Sleep variability over a 2-week period is associated with restfulness and intrinsic limbic network connectivity in adolescents.

STUDY OBJECTIVES: Sleep duration and intraindividual variability in sleep duration undergo substantial changes in adolescence and impact brain and behavioral functioning. Although experimental work has linked acute sleep deprivation to heightened limbic responding and reduced regulatory control, there is limited understanding of how variability in sleep patterns might interact with sleep duration to influence adolescent functioning. This is important for optimal balancing of length and consistency of sleep. Here, we investigated how objective indices of sleep duration and variability relate to stress, restfulness, and intrinsic limbic network functioning in adolescents. METHODS: A sample of 101 adolescents ages 14-18 reported their stressors, after which they wore wrist actigraph watches to monitor their sleep and rated their restfulness every morning over a 2-week period. They also completed a resting-state fMRI scan. RESULTS: Adolescents reporting more stress experienced shorter sleep duration and greater sleep variability over the 2-week period. Longer nightly sleep duration was linked to feeling more rested the next morning, but this effect was reduced in adolescents with high cumulative sleep variability. Sleep variability showed both linear and quadratic effects on limbic connectivity: adolescents with high sleep variability exhibited more connectivity within the limbic network and less connectivity between the limbic and frontoparietal networks than their peers, effects which became stronger once variability exceeded an hour. CONCLUSIONS: Results suggest that cumulative sleep variability is related to stress and limbic network connectivity and shows interactive effects with sleep duration, highlighting the importance of balancing length and consistency of sleep for optimal functioning in adolescence.

Stronger mentalizing network connectivity in expectant fathers predicts postpartum father-infant bonding and parenting behavior.

Fathers play a critical role in parenting and in shaping child outcomes. However, the neurobiological underpinnings of successful adjustment to fatherhood have not been well-specified. Empathy and mentalizing abilities may characterize more effective fathering. These abilities may be supported by the functional connectivity (FC) of brain regions associated with social cognition and executive control. We used a seed-region-based approach to assess resting-state FC (rsFC) of the medial prefrontal cortex (mPFC) in 40 expectant fathers. We tested associations between mPFC whole-brain rsFC and fathers' self-report measures of empathy during pregnancy, as well as their ratings of father-infant bonding and fathering behaviors at six months postpartum. Stronger prenatal rsFC between the mPFC and precuneus, frontal pole, planum polare, and orbitofrontal cortex (OFC) was negatively associated with self-reported empathic concern and perspective-taking, whereas mPFC rsFC with the lateral occipital cortex (LOC) was positively associated with self-reported perspective-taking. Additionally, stronger prenatal connectivity between the mPFC rsFC and the superior parietal lobule and LOC regions predicted father reports of postpartum bonding with infants, and stronger prenatal mPFC rsFC with the LOC predicted more effective postpartum parenting. This study is the first to measure rsFC in expectant fathers as a predictor of subsequent adjustment to fathering.

Theory of mind processing in expectant fathers: Associations with prenatal oxytocin and parental attunement.

Social cognition may facilitate fathers' sensitive caregiving behavior. We administered the Why-How Task, an fMRI task that elicits theory of mind processing, to expectant fathers (n = 39) who also visited the laboratory during their partner's pregnancy and provided a plasma sample for oxytocin assay. Three months postpartum, fathers reported their beliefs about parenting. When rating "Why" an action was being performed versus "How" the action was being performed (Why > How contrast), participants showed activation in regions theorized to support theory of mind, including the dorsomedial prefrontal cortex and superior temporal sulcus. Fathers' prenatal oxytocin levels predicted greater signal change during the Why > How contrast in the inferior parietal lobule. Both prenatal oxytocin and attunement parenting beliefs were associated with Why > How activation in the dorsolateral prefrontal cortex, a theory of mind region implicated in emotion regulation. Posterior parahippocampal gyrus and dorsolateral prefrontal cortex activation during the Why > How contrast predicted fathers' attunement parenting beliefs. In conclusion, fathers' neural activation when engaging in a theory of mind task was associated with their prenatal oxytocin levels and their postpartum attunement parenting beliefs. Results suggest biological and cognitive components of fathering may track with the theory of mind processing.

Neural activity moderates the association between sleep and risky driving behaviors in adolescence.

The biological, environmental, and psychosocial changes that occur in adolescence engender an increase in risk taking often linked to the high rates of motor vehicle crashes amongst young drivers. Most U.S. adolescents suffer from poor sleep, which is known to exacerbate the risk of driving crashes; however, research has yet to uncover a neurobiological link between sleep and risky driving in adolescence. Here, we examined potential moderators of the sleep-risk relation in fifty-six adolescents (14-18y/o) as they completed a driving task during fMRI. While poor sleep was associated with increased risky driving (i.e., running more yellow lights), good sleep emerged as a novel buffer against risky driving in lower sensation-seeking adolescents. Neural activity in the ventral striatum (VS), a key node of the risk-taking circuit, also moderated the sleep-risk association: sleep was related to risk-taking in individuals demonstrating high, but not low, VS response during risky decision-making, suggesting that reward-related neural response may underly the connection between sleep and risk-taking in adolescence. This study sheds light on the risk of driving crashes in youth by highlighting sleep as both an exacerbator and a buffer of risky driving in adolescence. Taken together, these results underscore the importance of improving adolescent sleep.

How do expectant fathers respond to infant cry? Examining brain and behavioral responses and the moderating role of testosterone.

Expectant parents' responses to infant cry may indicate future risk and resiliency in the parent-child relationship. Most studies of parental reactivity to infant cry have focused on mothers, and few studies have focused on expectant fathers, although fathers make important contributions to parenting. Additionally, although different responses to infant cry (behavioral, psychological and neural) are hypothesized to track together, few studies have analyzed them concurrently. The current investigation aimed to address these gaps by characterizing multimodal responses to infant cry within expectant fathers and testing whether prenatal testosterone moderates these responses. Expectant fathers responded to infant cry vs frequency-matched white noise with increased activation in bilateral areas of the temporal lobe involved in processing speech sounds and social and emotional stimuli. Handgrip force, which has been used to measure parents' reactivity to cry sounds in previous studies, did not differentiate cry from white noise within this sample. Expectant fathers with higher prenatal testosterone showed greater activation in the supramarginal gyrus, left occipital lobe and precuneus cortex to cry sounds. Expectant fathers appear to interpret and process infant cry as a meaningful speech sound and social cue, and testosterone may play a role in expectant fathers' response to infant cry.

Physical home environment is associated with prefrontal cortical thickness in adolescents.

Biologically embedded experiences alter developmental trajectories in ways that can influence health, learning, and/or behavior. These systematic differences in experiences may contribute to different biological outcomes as individuals grow and develop, including at the neural level. Previous studies of biologically embedded experiences on neurodevelopment have focused on large-scale institutional or economic factors (e.g. socioeconomic status [SES]) and psychosocial factors (e.g. caregiving behavior). Less attention has focused on how the quality of the immediate home settings, such as the physical home environment (PHYS), influences neurodevelopment. Moreover, no study has investigated these effects in adolescents, who undergo significant physical maturation and neurodevelopment that may influence how they respond to their physical environments. The goal of the current study was to examine whether PHYS quality is biologically embedded in the developing adolescent brain as evidenced by cognitive achievement and cortical development in 56 (48% female) healthy adolescents (14-18 years (M = 16.83 years, SD = 1.17). Using in-home assessments of the physical home environment, anatomical brain scans, and indices of academic achievement, we found that adolescents who have more physical problems in the home (e.g. structural hazards, crowding, excessive noise, poorly lit) have thinner prefrontal cortices, which was associated with lower levels of reading achievement, independent of SES and psychosocial factors. By conducting home visits to assess physical characteristics of adolescents' home, we highlight a typically overlooked aspect of the home environment that has relevance for adolescents' cognitive and brain development.

The transition to parenthood as a critical window for adult health.

Becoming a parent is a transformative experience, marked by hormonal changes and neuroplasticity as well as shifts in self-concept, social roles, and daily routines. Although the arrival of a new baby is often a joyful event, the postpartum period can also be a time of heightened psychosocial stress and health behavior changes, including significant sleep disruption and decreased physical activity. Markers of allostatic load, such as physiological stress and inflammation, may also become dysregulated during this time. Given these neurobiological, psychosocial, and behavioral changes, the transition to parenthood may shape health trajectories in midlife. For many mothers and fathers, the transition to parenthood represents an inflection point for obesity, such that perinatal weight gains are retained long-term. Similarly, many individuals experience their 1st episode of major depression during the postpartum period. In sum, the transition to parenthood may represent a critical window for determining both mental and physical health in midlife and beyond. Physical and mental health problems over the transition to parenthood may be exacerbated for parents without access to protected, paid time off from employment. Known disparities in mood disorders, obesity, and allostatic load may be linked to risk factors stemming from the perinatal period. This article relates the importance of the transition to parenthood to population health and discusses parental leave policy as an example of an initiative that can support parents and relieve stress during the perinatal period. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Sleep quality and adolescent default mode network connectivity.

Sleep suffers during adolescence and is related to academic, emotional and social behaviors. How this normative change relates to ongoing brain development remains unresolved. The default mode network (DMN), a large-scale brain network important for complex cognition and socioemotional processing, undergoes intra-network integration and inter-network segregation during adolescence. Using resting state functional connectivity and actigraphy over 14 days, we examined correlates of naturalistic individual differences in sleep duration and quality in the DMN at rest in 45 human adolescents (ages 14-18). Variation in sleep quality, but not duration, was related to weaker intrinsic DMN connectivity, such that those with worse quality sleep evinced weaker intra-network connectivity at rest. These novel findings suggest sleep quality, a relatively unexplored sleep index, is related to adolescent brain function in a network that contributes to behavioral maturation and undergoes development during adolescence.

Neural connectivity moderates the association between sleep and impulsivity in adolescents.

Adolescence is characterized by chronic insufficient sleep and extensive brain development, but the relation between adolescent sleep and brain function remains unclear. We report the first functional magnetic resonance imaging study to investigate functional connectivity as a moderator between sleep and impulsivity, a problematic behavior during this developmental period. Naturalistic differences in sleep have not yet been explored as treatable contributors to adolescent impulsivity. Although public and scientific attention focuses on sleep duration, we report individual differences in sleep quality, not duration, in fifty-five adolescents (ages 14-18) yielded significant differences in functional connectivity between the prefrontal cortex and default mode network. Poor sleep quality was related to greater affect-related impulsivity among adolescents with low, but not high, connectivity, suggesting neural functioning relates to individual differences linking sleep quality and impulsivity. Response inhibition and cognitive impulsivity were not related to sleep quality, suggesting that sleep has a greater impact on affect-related impulsivity. Exploring environmental contributors of poor sleep quality, we demonstrated pillow comfort was uniquely related to sleep quality over age, sex, and income, a promising advance ripe for intervention.

Greater response variability in adolescents is associated with increased white matter development.

Adolescence is a period of learning, exploration, and continuous adaptation to fluctuating environments. Response variability during adolescence is an important, understudied, and developmentally appropriate behavior. The purpose of this study was to identify the association between performance on a dynamic risky decision making task and white matter microstructure in a sample of 48 adolescents (14-16 years). Individuals with the greatest response variability on the task obtained the widest range of experience with potential outcomes to risky choice. When compared with their more behaviorally consistent peers, adolescents with greater response variability rated real-world examples of risk taking behaviors as less risky via self-report. Tract-Based Spatial Statistics (TBSS) were used to examine fractional anisotropy (FA) and mean diffusivity (MD). Greater FA in long-range, late-maturing tracts was associated with higher response variability. Greater FA and lower MD were associated with lower riskiness ratings of real-world risky behaviors. Results suggest that response variability and lower perceived risk attitudes of real-world risk are supported by neural maturation in adolescents.

Neural mechanisms of social influence in adolescence.

During the transformative period of adolescence, social influence plays a prominent role in shaping young people's emerging social identities, and can impact their propensity to engage in prosocial or risky behaviors. In this study, we examine the neural correlates of social influence from both parents and peers, two important sources of influence. Nineteen adolescents (age 16-18 years) completed a social influence task during a functional magnetic resonance imaging (fMRI) scan. Social influence from both sources evoked activity in brain regions implicated in mentalizing (medial prefrontal cortex, left temporoparietal junction, right temporoparietal junction), reward (ventromedial prefrontal cortex), and self-control (right ventrolateral prefrontal cortex). These results suggest that mental state reasoning, social reward and self-control processes may help adolescents to evaluate others' perspectives and overcome the prepotent force of their own antecedent attitudes to shift their attitudes toward those of others. Findings suggest common neural networks involved in social influence from both parents and peers.

Sleep variability in adolescence is associated with altered brain development.

Despite the known importance of sleep for brain development, and the sharp increase in poor sleep during adolescence, we know relatively little about how sleep impacts the developing brain. We present the first longitudinal study to examine how sleep during adolescence is associated with white matter integrity. We find that greater variability in sleep duration one year prior to a DTI scan is associated with lower white matter integrity above and beyond the effects of sleep duration, and variability in bedtime, whereas sleep variability a few months prior to the scan is not associated with white matter integrity. Thus, variability in sleep duration during adolescence may have long-term impairments on the developing brain. White matter integrity should be increasing during adolescence, and so sleep variability is directly at odds with normative developmental trends.

The use of functional and effective connectivity techniques to understand the developing brain.

Developmental neuroscience, the study of the processes that shape and reshape the maturing brain, is a growing field still in its nascent stages. The developmental application of functional and effective connectivity techniques, which are tools that measure the interactions between elements of the brain, has revealed insight to the developing brain as a complex system. However, this insight is granted in discrete windows of consecutive time. The current review uses dynamic systems theory as a conceptual framework to understand how functional and effective connectivity tools may be used in conjunction to capture the dynamic process of change that occurs with development.

Adolescents' emotional competence is associated with parents' neural sensitivity to emotions.

An essential component of youths' successful development is learning to appropriately respond to emotions, including the ability to recognize, identify, and describe one's feelings. Such emotional competence is thought to arise through the parent-child relationship. Yet, the mechanisms by which parents transmit emotional competence to their children are difficult to measure because they are often implicit, idiosyncratic, and not easily articulated by parents or children. In the current study, we used a multifaceted approach that went beyond self-report measures and examined whether parental neural sensitivity to emotions predicted their child's emotional competence. Twenty-two adolescent-parent dyads completed an fMRI scan during which they labeled the emotional expressions of negatively valenced faces. Results indicate that parents who recruited the amygdala, VLPFC, and brain regions involved in mentalizing (i.e., inferring others' emotional states) had adolescent children with greater emotional competence. These results held after controlling for parents' self-reports of emotional expressivity and adolescents' self-reports of the warmth and support of their parent relationships. In addition, adolescents recruited neural regions involved in mentalizing during affect labeling, which significantly mediated the associated between parental neural sensitivity and adolescents' emotional competence, suggesting that youth are modeling or referencing their parents' emotional profiles, thereby contributing to better emotional competence.

Neural mechanisms of impulse control in sexually risky adolescents.

The consequences of risky sexual behavior are of public concern. Adolescents contribute disproportionately to negative consequences of risky sexual behavior. However, no research has examined the neural correlates of impulse control and real-world engagement in risky sexual behavior in this population. The aim of the present study was to examine this question. Twenty sexually active adolescents performed an impulse control task during a functional magnetic resonance imaging (fMRI) scan and risky sexual behaviors were assessed through self-report. Sexual riskiness ratings were negatively associated with activation in the prefrontal cortex during response inhibition. These results suggest that diminished engagement of impulse control circuitry may contribute to sexual riskiness in adolescents.

Altered cerebral blood flow and neurocognitive correlates in adolescent cannabis users.

RATIONALE: The effects of adolescent marijuana use on the developing brain remain unclear, despite its prevalence. Arterial spin labeling (ASL) is a noninvasive imaging technique that characterizes neurovascular status and cerebral blood flow (CBF), potentially revealing contributors to neuropathological alterations. No studies to date have looked at CBF in adolescent marijuana users. OBJECTIVES: This study examined CBF in adolescent marijuana users and matched healthy controls at baseline and after 4 weeks of monitored abstinence. METHODS: Heavy adolescent marijuana users (n = 23, >200 lifetime marijuana use days) and demographically matched controls (n = 23) with limited substance exposure underwent an ASL brain scan at an initial session and after 4 weeks of sequential urine toxicology to confirm abstinence. RESULTS: Marijuana users showed reduced CBF in four cortical regions including the left superior and middle temporal gyri, left insula, left and right medial frontal gyrus, and left supramarginal gyrus at baseline; users showed increased CBF in the right precuneus at baseline, as compared to controls (corrected p values < 0.05). No between group differences were found at follow-up. CONCLUSIONS: Marijuana use may influence CBF in otherwise healthy adolescents acutely; however, group differences were not observed after several weeks of abstinence. Neurovascular alterations may contribute to or underlie changes in brain activation, neuropsychological performance, and mood observed in young cannabis users with less than a month of abstinence.

Frequency drives lexical access in reading but not in speaking: the frequency-lag hypothesis.

To contrast mechanisms of lexical access in production versus comprehension we compared the effects of word frequency (high, low), context (none, low constraint, high constraint), and level of English proficiency (monolingual, Spanish-English bilingual, Dutch-English bilingual) on picture naming, lexical decision, and eye fixation times. Semantic constraint effects were larger in production than in reading. Frequency effects were larger in production than in reading without constraining context but larger in reading than in production with constraining context. Bilingual disadvantages were modulated by frequency in production but not in eye fixation times, were not smaller in low-constraint contexts, and were reduced by high-constraint contexts only in production and only at the lowest level of English proficiency. These results challenge existing accounts of bilingual disadvantages and reveal fundamentally different processes during lexical access across modalities, entailing a primarily semantically driven search in production but a frequency-driven search in comprehension. The apparently more interactive process in production than comprehension could simply reflect a greater number of frequency-sensitive processing stages in production.