Tyvaso DPI: Drug-device characteristics and patient clinical considerations.

Tyvaso DPI is a drug-device combination therapy comprised of a small, portable, reusable, breath-powered, dry powder inhaler (DPI) for the delivery of treprostinil. It is approved for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. Tyvaso DPI utilizes single-use prefilled cartridges to ensure proper dosing. Unlike nebulizer devices, administration of Tyvaso DPI is passive and does not require coordination with the device. The low-flow rate design results in targeted delivery to the peripheral lungs due to minimal drug loss from impaction in the oropharynx. The inert fumaryl diketopiperazine (FDKP) excipient forms microparticles that carry treprostinil into the airways, with a high fraction of the particles in the respirable range. In a clinical study in patients with pulmonary arterial hypertension, Tyvaso DPI had similar exposure and pharmacokinetics, low incidence of adverse events, and high patient satisfaction compared with nebulized treprostinil solution. Tyvaso DPI may be considered as a first prostacyclin agent or for those that do not tolerate other prostacyclin formulations, patients with pulmonary comorbidities, patients with mixed Group 1 and Group 3 pulmonary hypertension, or those that prefer an active lifestyle and need a portable, non-invasive treatment. Tyvaso DPI is a patient-preferred, maintenance-free, safe delivery option that may improve patient compliance and adherence.

Comparing Inertial Measurement Units to Markerless Video Analysis for Movement Symmetry in Quarter Horses.

BACKGROUND: With an increasing number of systems for quantifying lameness-related movement asymmetry, between-system comparisons under non-laboratory conditions are important for multi-centre or referral-level studies. This study compares an artificial intelligence video app to a validated inertial measurement unit (IMU) gait analysis system in a specific group of horses. METHODS: Twenty-two reining Quarter horses were equipped with nine body-mounted IMUs while being videoed with a smartphone app. Both systems quantified head and pelvic movement symmetry during in-hand trot (hard/soft ground) and on the lunge (left/right rein, soft ground). Proportional limits of agreement (pLoA) were established. RESULTS: Widths of pLoA were larger for head movement (29% to 50% in-hand; 22% to 38% on lunge) than for pelvic movement (13% to 24% in-hand; 14% to 24% on lunge). CONCLUSION: The between-system pLoAs exceed current "lameness thresholds" aimed at identifying the affected limb(s) in lame horses. They also exceed published limits of agreement for stride-matched data but are similar to repeatability values and "lameness thresholds" from "non-lame" horses. This is encouraging for multi-centre studies and referral-level veterinary practice. The narrower pLoA values for pelvic movement asymmetry are particularly encouraging, given the difficulty of grading hind limb lameness "by eye".

CaPTure: Calcium PeakToolbox for analysis of in vitro calcium imaging data.

BACKGROUND: Calcium imaging is a powerful technique for recording cellular activity across large populations of neurons. However, analysis methods capable of single-cell resolution in cultured neurons, especially for cultures derived from human induced pluripotent stem cells (hiPSCs), are lacking. Existing methods lack scalability to accommodate high-throughput comparisons between multiple lines, across developmental timepoints, or across pharmacological manipulations. RESULTS: To address this need we developed CaPTure, a scalable, automated Ca2+ imaging analysis pipeline ( https://github.com/LieberInstitute/CaPTure ). CaPTuredetects neurons, classifies and quantifies spontaneous activity, quantifies synchrony metrics, and generates cell- and network-specific metrics that facilitate phenotypic discovery. The method is compatible with parallel processing on computing clusters without requiring significant user input or parameter modification. CONCLUSION: CaPTure allows for rapid assessment of neuronal activity in cultured cells at cellular resolution, rendering it amenable to high-throughput screening and phenotypic discovery. The platform can be applied to both human- and rodent-derived neurons and is compatible with many imaging systems.

A clinical trial comparing trauma-informed guilt reduction therapy (TrIGR), a brief intervention for trauma-related guilt, to supportive care therapy.

INTRODUCTION: Trauma-related guilt is common, associated with posttraumatic mental health problems, and can persist after posttraumatic stress disorder (PTSD) treatment. We compared the efficacy of two six-session psychotherapies, Trauma-Informed Guilt Reduction (TrIGR) and Supportive Care Therapy (SCT), for reducing trauma-related guilt. TrIGR helps patients accurately appraise their role in the trauma and re-engage in values. In SCT, patients guide session content. METHODS: A total of 184 veterans seeking VA mental health services were enrolled across two sites; 145 veterans (mean age: 39.2 [8.1]; 92.4% male; 84.8% with PTSD) who endorsed guilt related to a traumatic event that occurred during a post 9/11 Iraq or Afghanistan deployment were randomized and assessed at baseline, posttreatment, 3- and 6-month follow-up. RESULTS: Linear mixed models using intent-to-treat analyses showed guilt decreased in both conditions with a greater decrease for TrIGR (treatment × time, -0.22; F 1, 455.2 = 18.49, p = .001; d = 0.92) than supportive therapy. PTSD and depressive symptoms showed the same pattern. TrIGR had significantly higher likelihood of PTSD treatment response (67% vs. 40%), loss of PTSD diagnosis (50% vs. 14%), and meaningful change in depression (54% vs. 27%) than supportive therapy. Psychological distress and trait shame improved in both conditions. Quality of life did not change. CONCLUSIONS: Targeting guilt appears to be an effective means for reducing posttraumatic symptoms and distress.

Short-chain fatty acid butyrate, a breast milk metabolite, enhances immature intestinal barrier function genes in response to inflammation in vitro and in vivo.

Infants born under 1,500 g have an increased incidence of necrotizing enterocolitis in the ileum and the colon, which is a life-threatening intestinal necrosis. This is in part due to excessive inflammation in the immature intestine to colonizing bacteria because of an immature innate immune response. Breastmilk complex carbohydrates create metabolites of colonizing bacteria in the form of short-chain fatty acids (SCFAs). We studied the effect of breastmilk metabolites, SCFAs, on immature intestine with regard to anti-inflammatory effects. This showed that acetate, propionate, and butyrate were all anti-inflammatory to an IL-1ß inflammatory stimulus. In this study, to further define the mechanism of anti-inflammation, we created transcription profiles of RNA from immature human enterocytes after exposure to butyrate with and without an IL-1ß inflammatory stimulus. We demonstrated that butyrate stimulates an increase in tight-junction and mucus genes and if we inhibit these genes, the anti-inflammatory effect is partially lost. SCFAs, products of microbial metabolism of complex carbohydrates of breastmilk oligosaccharides, have been found with this study to induce an anti-IL-1ß response that is associated with an upregulation of tight junctions and mucus genes in epithelial cells (H4 cells). These studies suggest that breastmilk in conjunction with probiotics can reduce excessive inflammation with metabolites that are anti-inflammatory and stimulate an increase in the mucosal barrier.NEW & NOTEWORTHY This study extends previous observations to define the anti-inflammatory properties of butyrate, a short-chain fatty acid produced by the metabolism of breastmilk oligosaccharides by colonizing bacteria. Using transcription profiling of immature enterocyte genes, after exposure to butyrate and an IL-1ß stimulus, we showed that tight-junction genes and mucus genes were increased, which contributed to the anti-inflammatory effect.

Improving Quality of Care Through a Mandatory Provincial Audit Program: Ontario's Emergency Department Return Visit Quality Program.

The Emergency Department Return Visit Quality Program was launched in Ontario, Canada, to promote a culture of quality. It mandates the province's largest-volume emergency departments (EDs) to audit charts of patients who had a return visit leading to hospital admission, including some of their 72-hour all-cause return visits with admission and all of their 7-day ones with sentinel diagnoses (ie, acute myocardial infarction, subarachnoid hemorrhage, and pediatric sepsis), and submit their findings to a governmental agency. This provides an opportunity to identify possible adverse events and quality issues, which hospitals can then address through quality improvement initiatives. A group of emergency physicians with quality improvement expertise analyzed the submitted audits and accompanying narrative templates, using a general inductive approach to develop a novel classification of recurrent quality themes. Since the Return Visit Quality Program launched in 2016, 125,698 return visits with admission have been identified, representing 0.93% of the 86 participating EDs' 13,559,664 visits. Overall, participating hospitals have conducted 12,852 detailed chart audits, uncovering 3,010 (23.4%) adverse events/quality issues and undertaking hundreds of quality improvement provincewide projects as a result. The inductive analysis revealed 11 recurrent themes, classified into 3 groupings: patient characteristics (ie, patient risk profile and elder care), ED team actions or processes (ie, physician cognitive lapses, documentation, handover/communication between providers, radiology, vital signs, and high-risk medications or medication interactions), and health care system issues (ie, discharge planning/community follow-up, left against medical advice/left without being seen, and imaging/testing availability). The Return Visit Quality Program is the largest mandatory audit program for EDs and provides a novel approach to identify local adverse events/quality issues to target for improved patient safety and quality of care. It provides a blueprint for health system leaders to enable clinicians to develop an approach to organizational quality, as well as for teams to construct an audit system that yields defined issues amenable to improvement.

Comparing Exposure- and Coping Skills-Based Treatments on Trauma-Related Guilt in Veterans With Co-Occurring Alcohol Use and Posttraumatic Stress Disorders.

Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) commonly co-occur, and this comorbidity (PTSD-SUD) is associated with more severe symptoms and functional impairment than either disorder alone. Growing evidence indicates that trauma-related guilt, typically concerning negative appraisals of one's actions or inaction during a traumatic event, is associated with PTSD, depression, suicidality, and, possibly, substance use. The present study examined whether integrated treatment for PTSD-SUD was effective in reducing trauma-related guilt as measured by the Trauma-Related Guilt Inventory. Data were drawn from a randomized clinical trial comparing the effectiveness of two integrated therapies on treatment outcomes in a sample of U.S. veterans (N = 119) with comorbid PTSD and SUD. Participants were randomized to receive either Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE; n = 63) or Seeking Safety (SS; n = 56). The results indicated that global guilt decreased over time for the whole sample. However, there was a significant Treatment × Time interaction, such that participants in the COPE condition reported lower rates of global guilt, d = 0.940, over time compared to those in the SS condition, d = .498. To our knowledge, this was the first study to examine the effects of integrated PTSD-SUD treatment on trauma-related guilt. The findings highlight that exposure-based, trauma-focused treatment for comorbid PTSD-SUD can be more effective in decreasing trauma-related guilt, with potentially longer-lasting effects, than non-exposure-based treatment, adding evidence that patients with PTSD-SUD should be offered such treatment.

Residual Symptoms of Posttraumatic Stress Disorder and Alcohol Use Disorder Following Integrated Exposure Treatment Versus Coping Skills Treatment.

Although some studies have demonstrated residual symptoms in patients who have participated in posttraumatic stress disorder (PTSD) treatment, no studies to date have assessed residual PTSD symptoms following treatment for comorbid alcohol use disorder (AUD) and PTSD (PTSD/AUD). We examined residual symptoms of PTSD and AUD in 73 veterans with PTSD/AUD who completed a posttreatment assessment after being randomized to receive either Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) or Seeking Safety (SS). We used logistic regression to identify differences (a) in residual PTSD and AUD symptoms among participants randomized to COPE versus SS and (b) among those with versus without a posttreatment PTSD/AUD diagnosis within both treatment conditions. Participants randomized to SS were more likely to report persistent avoidance, inability to experience positive emotions, hypervigilance, difficulty concentrating, and difficulty sleeping, ORs = 3.74-6.21. There were no differences between COPE and SS regarding the likelihood of persistent AUD symptoms. Participants without a posttreatment PTSD diagnosis had lower conditional probabilities of most symptoms, although exaggerated startle, OR = 0.71, and irritability/aggression, OR = 0.58, were most likely to persist. Participants without a posttreatment AUD diagnosis had lower conditional probabilities of most symptoms, although withdrawal, OR = 0.21; unsuccessful quit attempts, OR = 0.04; and higher intake, OR = 0.01, were most likely to persist. Findings indicate hyperarousal may warrant additional intervention following PTSD treatment. Residual AUD symptoms may relate to the enduring nature of some AUD symptoms rather than a lack of treatment efficacy.

Histopathological and molecular predictors of growth patterns and recurrence in craniopharyngiomas: a systematic review.

Craniopharyngiomas (CPs) are rare, benign tumors derived from Rathke's pouch, known for their high recurrence rates and associated morbidity and mortality. Despite significant investigation on risk factors for recurrence, a lack of consensus persists. Recent research suggests that specific histopathological and molecular characteristics are prognostic for disease progression. In this systematic review, we analyzed and consolidated key features of CPs that contribute to increased recurrence rates. This systematic review was performed in accordance with PRISMA guidelines. A search string was created with the keywords "craniopharyngioma," "histology," "histopathology," "molecular," and "recurrence." Literature was collected from 2006 to 2016 on the PubMed/Medline and Web of Science databases. The initial search resulted in 242 papers, examined with inclusion and exclusion criteria. The final review included a total of 37 studies, 36 primary studies covering a total of 1461 patients and 1 previous meta-analysis. Cystic lesions and whorl-like arrays were found to be associated with increased recurrence, while previously considered reactive gliosis and finger-shaped protrusions were not. The genetic elements found to be associated with increased risk of recurrence were Ki-67, Ep-CAM, PTTG-1, survivin, and certain RAR isotypes, as well as the glycoproteins osteonectin and chemokines CXCL12/CXCR4. The effects of VEGF, HIF-1α, and p53, despite extensive study, yielded conflicting results. Certain histopathological and molecular characteristics of CPs provide insight into their pathogenesis, likelihood of recurrence, and potential novel targets for therapy.

Understanding the impact of attachment insecurity on PTSD symptoms among male Veterans and military personnel.

Attachment insecurity (i.e., attachment anxiety and attachment avoidance) has been found to contribute to PTSD symptom severity in Veterans. However, little is known of the unique contribution of attachment insecurity on individual PTSD symptom clusters. In a community sample of 106 combat-deployed Veterans, active duty service members, and reservists, this study examined: (1) the relationships between childhood family experience, combat experience, attachment insecurity, and PTSD symptom clusters, and (2) the influence of attachment insecurity on PTSD symptom clusters. Results revealed significant correlations between attachment anxiety and all PTSD symptom clusters (rs = .22 -.43) and attachment avoidance and PTSD symptom clusters, except the avoidance cluster (rs = .21 -.36). Four multiple regression analyses were employed to address the second study aim. Childhood family experiences predicted negative alterations in cognitions and mood (ß = -.30) and alterations in arousal and reactivity (ß = -.20). Further, combat experience significantly predicted each symptom cluster of PTSD (ßs = .03 -.44). In the second step, attachment anxiety and attachment avoidance were added to each model. Attachment anxiety and attachment avoidance predicted negative alterations in cognitions and mood (ßs = .22 and .35) and alterations in arousal and reactivity (ßs = .27 and .17). Inconsistent with previous research, attachment insecurity did not predict symptoms of avoidance. These results highlight the impact of attachment among a diverse sample of trauma exposed individuals and may provide insights for clinical implications and therapeutic approaches when working with Veterans and military personnel high in attachment insecurity.

Calibrating temperature reconstructions from fish otolith oxygen isotope analysis for California's critically endangered Delta Smelt.

RATIONALE: Oxygen isotope ratios (δ18 O values) of fish otoliths (ear bones) are valuable geochemical tracers of water conditions and thermal life history. Delta Smelt (Hypomesus transpacificus) are osmerid forage fish endemic to the San Francisco Estuary, California, USA, that are on the verge of extinction. These fish exhibit a complex life history that allows them to survive in a dynamic estuarine environment; however, a rapidly warming climate threatens this thermally sensitive species. Here we quantify the accuracy and precision of using δ18 O values in otoliths to reconstruct the thermal life histories of Delta Smelt. METHODS: Delta Smelt were reared for 360 days using three different water sources with different ambient δ18 Owater values (-8.75‰, -5.28‰, and -4.06‰) and different water temperatures (16.4°C, 16.7°C, 18.7°C, and 20.5°C). Samples were collected after 170 days (n = 28) and 360 days (n = 14) post-hatch. In situ δ18 O values were measured from the core of the otolith to the dorsal edge using secondary ion mass spectrometry (SIMS) to reconstruct temporally resolved thermal life histories. RESULTS: The δ18 Ootolith values for Delta Smelt varied as a linear inverse function of water temperature: 1000 ln α = 18.39 (±0.43, 1SE)(103 TK-1 ) - 34.56 (±1.49, 1SE) and δ18 Ootolith(VPDB) - δ18 Owater (VPDB) = 31.34(±0.09, 1SE) - 0.19(±0.01, 1SE) × T ° C. When the ambient δ18 Owater value is known, this species-specific temperature-dependent oxygen isotope fractionation model facilitated the accurate (0.25°C) and precise (±0.37°C, 2σ) reconstruction of the water temperature experienced by the fish. In contrast, the use of existing general fractionation equations resulted in inaccurate temperature reconstructions. CONCLUSIONS: The species-specific δ18 Ootolith fractionation equation allowed for accurate and precise reconstructions of water temperatures experienced by Delta Smelt. Characterization of ambient δ18 Owater values remains a critical next step for reconstructing thermal life histories of wild Delta Smelt. This tool will provide new insights into habitat utilization, potential thermal refugia, and resilience to future warming for this critically endangered fish.

Behavioural abnormalities in a novel mouse model for Silver Russell Syndrome.

Silver Russell Syndrome (SRS) syndrome is an imprinting disorder involving low birth weight with complex genetics and diagnostics. Some rare SRS patients carry maternally inherited microduplications spanning the imprinted genes CDKN1C, PHLDA2, SLC22A18 and KCNQ1, suggesting that overexpression of one of more of these genes contributes to the SRS phenotype. While this molecular alteration is very rare, feeding difficulties are a very common feature of this condition. Given that SRS children also have very low body mass index, understanding the underpinning biology of the eating disorder is important, as well as potential co-occurring behavioural alterations. Here, we report that a mouse model of this microduplication exhibits a number of behavioural deficits. The mice had a blunted perception of the palatability of a given foodstuff. This perception may underpin the fussiness with food. We additionally report hypoactivity, unrelated to anxiety or motoric function, and a deficit in the appropriate integration of incoming sensory information. Importantly, using a second genetic model, we were able to attribute all altered behaviours to elevated expression of a single gene, Cdkn1c. This is the first report linking elevated Cdkn1c to altered behaviour in mice. Importantly, the findings from our study may have relevance for SRS and highlight a potentially underreported aspect of this disorder.

Antarctic emerald rockcod have the capacity to compensate for warming when uncoupled from CO2 -acidification.

Increases in atmospheric CO2 levels and associated ocean changes are expected to have dramatic impacts on marine ecosystems. Although the Southern Ocean is experiencing some of the fastest rates of change, few studies have explored how Antarctic fishes may be affected by co-occurring ocean changes, and even fewer have examined early life stages. To date, no studies have characterized potential trade-offs in physiology and behavior in response to projected multiple climate change stressors (ocean acidification and warming) on Antarctic fishes. We exposed juvenile emerald rockcod Trematomus bernacchii to three PCO2 treatments (~450, ~850, and ~1,200 µatm PCO2 ) at two temperatures (-1 or 2°C). After 2, 7, 14, and 28 days, metrics of physiological performance including cardiorespiratory function (heart rate [fH ] and ventilation rate [fV ]), metabolic rate (M˙O2), and cellular enzyme activity were measured. Behavioral responses, including scototaxis, activity, exploration, and escape response were assessed after 7 and 14 days. Elevated PCO2 independently had little impact on either physiology or behavior in juvenile rockcod, whereas warming resulted in significant changes across acclimation time. After 14 days, fH , fV and M˙O2 significantly increased with warming, but not with elevated PCO2 . Increased physiological costs were accompanied by behavioral alterations including increased dark zone preference up to 14%, reduced activity by 12%, as well as reduced escape time suggesting potential trade-offs in energetics. After 28 days, juvenile rockcod demonstrated a degree of temperature compensation as fV , M˙O2, and cellular metabolism significantly decreased following the peak at 14 days; however, temperature compensation was only evident in the absence of elevated PCO2 . Sustained increases in fV and M˙O2 after 28 days exposure to elevated PCO2 indicate additive (fV ) and synergistic (M˙O2) interactions occurred in combination with warming. Stressor-induced energetic trade-offs in physiology and behavior may be an important mechanism leading to vulnerability of Antarctic fishes to future ocean change.

Juvenile Antarctic rockcod (Trematomus bernacchii) are physiologically robust to CO2-acidified seawater.

To date, numerous studies have shown negative impacts of CO2-acidified seawater (i.e. ocean acidification, OA) on marine organisms, including calcifying invertebrates and fishes; however, limited research has been conducted on the physiological effects of OA on polar fishes and even less on the impact of OA on early developmental stages of polar fishes. We evaluated aspects of aerobic metabolism and cardiorespiratory physiology of juvenile emerald rockcod, ITALIC! Trematomus bernacchii, an abundant fish in the Ross Sea, Antarctica, to elevated partial pressure of carbon dioxide ( ITALIC! PCO2 ) [420 (ambient), 650 (moderate) and 1050 (high) µatm ITALIC! PCO2 ] over a 1 month period. We examined cardiorespiratory physiology, including heart rate, stroke volume, cardiac output and ventilation rate, whole organism metabolism via oxygen consumption rate and sub-organismal aerobic capacity by citrate synthase enzyme activity. Juvenile fish showed an increase in ventilation rate under high ITALIC! PCO2 compared with ambient ITALIC! PCO2 , whereas cardiac performance, oxygen consumption and citrate synthase activity were not significantly affected by elevated ITALIC! PCO2 Acclimation time had a significant effect on ventilation rate, stroke volume, cardiac output and citrate synthase activity, such that all metrics increased over the 4 week exposure period. These results suggest that juvenile emerald rockcod are robust to near-future increases in OA and may have the capacity to adjust for future increases in ITALIC! PCO2  by increasing acid-base compensation through increased ventilation.

Effects of high temperatures on threatened estuarine fishes during periods of extreme drought.

Climate change and associated increases in water temperatures may impact physiological performance in ectotherms and exacerbate endangered species declines. We used an integrative approach to assess the impact of elevated water temperature on two fishes of immediate conservation concern in a large estuary system, the threatened longfin smelt (Spirinchus thaleichthys) and endangered delta smelt (Hypomesus transpacificus). Abundances have reached record lows in California, USA, and these populations are at imminent risk of extirpation. California is currently impacted by a severe drought, resulting in high water temperatures, conditions that will become more common as a result of climate change. We exposed fish to environmentally relevant temperatures (14°C and 20°C) and used RNA sequencing to examine the transcriptome-wide responses to elevated water temperature in both species. Consistent with having a lower temperature tolerance, longfin smelt exhibited a pronounced cellular stress response, with an upregulation of heat shock proteins, after exposure to 20°C that was not observed in delta smelt. We detected an increase in metabolic rate in delta smelt at 20°C and increased expression of genes involved in metabolic processes and protein synthesis, patterns not observed in longfin smelt. Through examination of responses across multiple levels of biological organization, and by linking these responses to habitat distributions in the wild, we demonstrate that longfin smelt may be more susceptible than delta smelt to increases in temperatures, and they have little room to tolerate future warming in California. Understanding the species-specific physiological responses of sensitive species to environmental stressors is crucial for conservation efforts and managing aquatic systems globally.

Examining Pretreatment Differences Between Veterans in Residential Versus Outpatient Treatment for Alcohol Use Disorder and Comorbid Combat-Related PTSD.

OBJECTIVE: Veterans with alcohol use disorder (AUD) and co-occurring posttraumatic stress disorder (PTSD) have access to various residential and outpatient treatment programs through the VA Healthcare System. There is a need to better understand the characteristics and needs of veterans who engage in residential versus outpatient treatment in order to help inform veteran care and decisions about treatment services. METHODS: The present study examined whether veterans with both AUD and combat-related PTSD who were enrolled in residential (n = 103) or outpatient treatment programs (n = 76) differed on pretreatment psychiatric symptoms, substance use and associated problems/behaviors, or demographics. Veterans completed self-report measures (which referenced symptoms in the past 30 days or 2 weeks) within the first week of PTSD/AUD treatment. RESULTS: Veterans in residential treatment had slightly worse PTSD symptoms compared to outpatient veterans; the groups reported similar levels of depression symptoms. Residential veterans had higher frequency of drug use, were more confident in their ability to be abstinent, attended more self-help meetings, spent more time around risky people or places, were more satisfied with their progress toward recovery goals, were more bothered by arguments with family/friends, and spent fewer days at work or school compared to outpatient veterans; the groups did not differ on drinking (frequency of use, binge drinking) or cravings. With respect to demographics, residential veterans were more likely to be married and non-Hispanic Caucasian (rather than minority races/ethnicities) compared to outpatient veterans. CONCLUSIONS: The finding that PTSD symptoms were more severe among veterans in residential substance use treatment highlights the importance of taking advantage of this crucial opportunity to engage veterans in evidence-based PTSD treatment. Consistent with other research, findings also indicated that individuals entering residential care have a higher level of impairment than those beginning outpatient care.

Structural and neurochemical correlates of individual differences in gamma frequency oscillations in human visual cortex.

Neuronal oscillations in the gamma frequency range play an important role in stimulus processing in the brain. The frequency of these oscillations can vary widely between participants and is strongly genetically determined, but the cause of this variability is not understood. Previous studies have reported correlations between individual differences in gamma frequency and the concentration of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), as well as with age and primary visual cortex (V1) area and thickness. This study assessed the relationships between all of these variables in the same group of participants. There were no significant correlations between gamma frequency and GABA+ concentration, V1 area or V1 thickness, although the relationship with GABA+/Cr approached significance. Considering age as a covariate further reduced the strength of all correlations and, in an additional dataset with a larger age range, gamma frequency was strongly inversely correlated with age but not V1 thickness or area, suggesting that age modulates gamma frequency via an additional, as yet unknown, mechanism. Consistent with other recent studies, these findings do not demonstrate a clear relationship between gamma frequency and GABA+ concentration. Further investigation of additional variables and the interactions between them will be necessary in order to more accurately determine predictors of the frequency of gamma oscillations.

Modelling the genetic contribution to mental illness: a timely end for the psychiatric rodent?

Rodent models are a key factor in the process of translating psychiatric genetics and genomics findings, allowing us to shed light on how risk-genes confer changes in neurobiology by merging different types of data across fields, from behavioural neuroscience to the burgeoning omics (e.g. genomics, epigenomics, proteomics, etc.). Moreover, they also provide an indispensable first step for drug discovery. However, recent evidence from both clinical and genetic studies highlights possible limitations in the current methods for classifying psychiatric illness, as both symptomology and underlying genetic risk are found to increasingly overlap across disorder diagnoses. Meanwhile, integration of data from animal models across disorders is currently limited. Here, we argue that behavioural neuroscience is in danger of missing informative data because of the practice of trying to 'diagnose' an animal model with a psychiatric illness. What is needed is a shift in emphasis, from seeking to ally an animal model to a specific disorder, to one focused on a more systematic assessment of the neurobiological and behavioural outcomes of any given genetic or environmental manipulation.

A Case of Pedunculated Adenoma of the Bile Duct Proving Adenoma to Cancer Sequence.

Ampullary adenocarcinoma is a rare malignancy that originates in the ampulla of Vater. It typically presents in the seventh decade of life. This condition shares overlapping features with periampullary tumors such as pancreatic cancer, but treatment modalities and prognosis vary. Histology will demonstrate either intestinal or pancreato-biliary epithelial subtype in ampullary adenocarcinoma. Despite its rare occurrence, ampullary adenocarcinoma should be included as a differential in elderly patients presenting with biliary obstruction. This case presentation is unique as it highlights the importance of histopathological findings and their progression. In this case, initial histology results revealed tubulovillous adenomatous polyps, but later biopsies revealed adenocarcinoma cells. These findings suggest that ampullary adenocarcinoma and several gastrointestinal cancers share a similar mechanism of action as it is related to the adenoma-to-carcinoma sequence. This case presentation aims to highlight the rare occurrence of this phenomenon at the ampulla of Vater.

Acute Burn Care.

LEARNING OBJECTIVES: After studying this article and viewing the videos, the participant should be able to: 1. Describe the current epidemiology of burn injuries. 2. Understand burn pathophysiology and perform a wound assessment. 3. Summarize the initial emergency management of a burn patient. 4. Calculate the anticipated fluid resuscitation requirements for a burn injury, and diagnose the complications of overresuscitation. 5. Describe the diagnosis and management of inhalation injury. 6. List the goals of wound care for superficial and deep burns, and describe the closed dressing technique. 7. Perform excision of a burn wound. 8. Compare various wound closure techniques using autografts and skin substitutes. SUMMARY: Plastic surgeons are essential members of the multidisciplinary burn team. Burn injuries remain common, and plastic surgeons have an opportunity to develop and innovate the field of acute burn care in light of workforce shortages. Burn pathophysiology is complex and dynamic, which informs the challenges encountered during the perioperative phase. Accurate burn wound assessment remains difficult, with implications for diagnosis and management. A systematic approach is required when stabilizing a major burn and/or inhalation injury with newly updated fluid resuscitation and triage guidelines. Wound care continues to evolve, with an emphasis on a closed dressing technique. For deeper burns, new surgical techniques are emerging for surgical débridement, along with improvements to traditional methods of tangential excision. Following excision, a number of established and novel techniques are available to close the wound with either autografts or skin substitutes.