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Background: Though artificial intelligence ("AI") has been increasingly applied to patient care, many of these predictive models are retrospective and not readily available for real-time decision-making. This survey-based study aims to evaluate implementation of a new, validated mortality risk calculator (Parkland Trauma Index of Mortality, "PTIM") embedded in our electronic healthrecord ("EHR") that calculates hourly predictions of mortality with high sensitivity and specificity. Methods: This is a prospective, survey-based study performed at a level 1 trauma center. An anonymous survey was sent to surgical providers and regarding PTIM implementation. The PTIM score evaluates 23 variables including Glasgow Coma Score (GCS), vital signs, and laboratory data. Results: Of the 40 completed surveys, 35 reported using PTIM in decision-making. Prior to reviewing PTIM, providers identified perceived top 3 predictors of mortality, including GCS (22/38, 58%), age (18/35, 47%), and maximum heart rate (17/35, 45%). Most providers reported the PTIM assisted their treatment decisions (27/35, 77%) and timing of operative intervention (23/35, 66%). Many providers agreed that PTIM integrated into rounds and patient assessment (22/36, 61%) and that it improved efficiency in assessing patients' potential mortality (21/36, 58%). Conclusions: Artificial intelligence algorithms are mostly retrospective and lag in real-time prediction of mortality. To our knowledge, this is the first real-time, automated algorithm predicting mortality in trauma patients. In this small survey-based study, we found PTIM assists in decision-making, timing of intervention, and improves accuracy in assessing mortality. Next steps include evaluating the short- and long-term impact on patient outcomes. [ABSTRACT FROM AUTHOR]

Despite advances in telemedicine, practices remain diverse, ranging from telephonic to still images and video-based conferencing. We review the various modes of telemedicine in burn care and summarize relevant studies, including their contributions and limitations. We also review the role of a more recent technology, augmented reality, and its role in the triage and management of burn patients. Telemedicine in burn care remains diverse, with varied outcomes in accuracy and efficiency. Newer technologies such as augmented reality have not been extensively studied or implemented but show promise in immersive, real-time triage. [ABSTRACT FROM AUTHOR]

Objective: We assessed the impact of a workshop on first-year medicine residents (PGY1) shared decision-making (SDM) communication skill, risk-benefit education, and attitude.Methods: A SDM skills-focused workshop was integrated into an academic medical center PGY1 ambulatory rotation in 2016-2017. Pre/post recordings of virtual Objective Structured Clinical Examinations (OSCEs) with standardized patients sharing decisions were scored using OPTION5. Risk-benefit education, including decision aid use, was measured. Pre/post surveys assessed SDM practice attitudes and perceived barriers.Results: 31 of 48 (65%) PGY1 workshop attendees completed pre/post OSCEs yielding 62 videos. OPTION5 scores improved from 27/100 pre to 56/100 post (p < 0.001). Pre/post increases in integration of qualitative (15/31 vs 31/31, p < 0.001) and quantitative (3/31 vs 31/31, p < 0.001) risk measures, and decision aids (1/3 vs 31/31, p < 0.001) were observed. Pro-SDM attitude of decisional neutrality increased 16.6% pre to 71.9% post-survey (P < 0.001). Barriers to SDM remain.Conclusion: This PGY1 workshop with virtual OSCEs improved SDM communication skills, the ability to find and provide risk-benefit education, and SDM-facilitating attitude.Practice Implications: Residency programs can improve SDM skills, risk-benefit education, and attitudes with a workshop intervention. Perceived time constraints and cognitive biases regarding risk-benefit estimates should be addressed to ensure quality SDM in practice. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbances are frequently reported in patients with major depressive disorder. We aimed to investigate the effects of vortioxetine on sleep quality and association between changes in sleep and treatment response.Methods: This study is a post-hoc analysis of a clinical trial that sought to evaluate the sensitivity to cognitive change of THINC-integrated tool in patients with major depressive disorder. In total, 92 patients (aged 18 to 65) meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for moderate or severe major depressive disorder and 54 healthy controls were included. All patients received open-label vortioxetine (10-20 mg/day, flexibly dosed) for 8 weeks. Herein, the primary outcomes of interest were changes in sleep, as measured by the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Insomnia Severity Index, between weeks 0, 2, and 8. The association between changes in sleep and depressive symptom severity was secondarily assessed.Results: We observed that sleep, as indicated by scores of Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Insomnia Severity Index, was significantly poorer in patients with major depressive disorder compared to healthy controls at weeks 0, 2, and 8 (p < 0.05). Among patients with major depressive disorder, we observed significant improvements on the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Insomnia Severity Index between weeks 0 and 8 (p < 0.05). We observed a significant association between improvements on the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Insomnia Severity Index and improvement of depressive symptoms.Conclusion: Improvement of depressive symptoms in major depressive disorder patients treated with vortioxetine was associated with significant improvements in sleep. Furthermore, improvements in sleep were predictive of antidepressant response and were linearly correlated with improvement in overall depressive symptom severity. [ABSTRACT FROM AUTHOR]

Highlights • MDD is a mental disorder characterized by aberrant emotion regulation. • Abnormal emotional control may result from dysfunctional cognitive processing. • The emotional response is comprised of affective and expressive components. • Lower limbic structures direct the expressive and affective components. • Higher cognitive structures allow for context-based emotional response modulation. Abstract Major depressive disorder (MDD) is a mental disorder characterized by aberrant emotion regulation. The capacity for emotion regulation stems from diverse neural circuits including higher level cognitive structures involved in processing contextual information, and lower level limbic structures involved in triggering emotional expression. Cognitive theories of depression posit that the MDD-specific abnormalities in emotional control derive itself from dysfunctional cognitive processes including biased attention, rumination, and altered information processing and memory. The main objectives of the current narrative review are to summarize the major neural systems involved in emotion regulation in humans, and to describe how these systems are dysregulated in MDD. The findings will be briefly discussed in the context of a conceptual framework of depression (i.e., Beck's cognitive model of depression), and neural targets of conventional treatments for depression will also be discussed. MDD exemplifies the critical importance of appropriate emotion regulation to human health and wellbeing, and demonstrates the personal and social impact of emotion dys regulation. [ABSTRACT FROM AUTHOR]

• Childhood maltreatment is an important stressor associated with stress & depression. • Stress- and depression-associated changes were mostly found in NRC31 and SLCA4. • Epigenetic changes occurring at different loci may have variable downstream effects. • Most studies measured epigenetic changes using peripheral tissue samples. • Future studies should evaluate epigenetic effects of psychotropic medication use. Environmental stressors, such as childhood maltreatment, have been recognized to contribute to the development of depression. Growing evidence suggests that epigenetic changes are a key mechanism by which stressors interact with the genome leading to stable changes in DNA structure, gene expression, and behaviour. The current review aimed to evaluate the relationship between stress-associated epigenetic changes and depression. Human studies were identified via systematic searching of PubMed/Medline from inception to February 2018. Seventeen articles were identified. Stress-associated epigenetic changes in the following genes were correlated with depression: NRC31, SLCA4, BDNF, FKBP5, SKA2, OXTR , LINGO3, POU3F1 and ITGB1. Epigenetic changes in glucocorticoid signaling (e.g., NR3C1, FKBP5), serotonergic signaling (e.g. SLC6A4), and neurotrophin (e.g., BDNF) genes appear to be the most promising therapeutic targets for future research. However, continued research is warranted due to inconsistent findings regarding the directionality of epigenetic modification. Future studies should also aim to control for the use of psychotropic agents due to their widespread use in depressed populations and established effects on DNA methylation. [ABSTRACT FROM AUTHOR]

Background: Compared to the 17-Item Hamilton Rating Scale for Depression (HAMD-17), the 7-Item Hamilton Rating Scale for Depression (HAMD-7) would be more practical for use in busy clinical settings. Herein, we aim to evaluate (1) whether the HAMD-7 is a reliable and valid measure that is sensitive to changes in depressive symptoms, and (2) whether early improvement of depressive symptoms, as measured by the HAMD-7, is capable of predicting response and remission in patients with major depressive disorder (MDD) during acute treatment with fluoxetine or electroconvulsive therapy (ECT).Methods: This is a post-hoc analysis of two clinical trials in MDD. Internal consistency, validity, and sensitivity-to-change of the HAMD-17 and HAMD-7 were compared during acute treatment and at 3-month follow-up. Receiver operating characteristic analyses were used to evaluate the discriminative capacity of the HAMD-17 and HAMD-7.Results: The HAMD-7 is a reliable and valid measure that is sensitive to changes in depressive symptoms. Early improvement, as measured by either the HAMD-17 or HAMD-7, was capable of predicting response and remission to acute treatment with fluoxetine or ECT with good discriminative capacity.Limitations: This is a post-hoc analysis of two open-label clinical trials with limited sample sizes. All patients were Taiwanese, which limits the generalizability of our results.Conclusions: HAMD-7 is a clinically useful measure that is capable of detecting early improvement of depressive symptoms. The HAMD-7 may have the potential to inform clinical assessment as part of measurement-based care. [ABSTRACT FROM AUTHOR]

Background Despite the widespread use of antidepressants in clinical practice, the current trial-and-error approach to medication selection contributes to treatment failure and underscores the need to identify reliable predictors of antidepressant response. Since changes in measures of cognition have been reported to occur early in treatment and prior to improvements in overall mood symptoms, the present review aims to determine whether early changes in measures of cognition can predict response in individuals with MDD. Methods A systematic review of studies evaluating early cognitive change as a predictor of later treatment response in MDD was conducted using PubMed/Medline, Embase and PsychINFO. Results A total of seven articles were identified. The available evidence suggests the early changes in cognition may predict treatment response in individuals with MDD. This was shown across antidepressant classes (i.e., SSRIs, SNRIs, NRIs, melatonergic antidepressants) and forms of therapy (i.e., pharmacotherapy, rTMS). The results depict an emerging trend towards early changes in facial emotion recognition (i.e., a hot cognitive process) as a predictor of treatment outcome. Limitations Our qualitative analysis reflects a very limited number of studies. Moreover, there was significant heterogeneity in the evaluation of cognition across studies. Future research should aim to parse out this heterogeneity by evaluating the relative predictive value of different measures of cognition. Conclusion The identification of reliable early treatment predictors of antidepressant response would be clinically significant, enabling clinicians to more accurately evaluate the efficacy of selected treatment avenues. [ABSTRACT FROM AUTHOR]

The management of traumatic colon injuries has evolved over the past two decades. Recent evidence suggests that primary repair or resection over colostomy may decrease morbidity and mortality. Data comparing patients undergoing primary repair versus resection are lacking. We sought to compare the outcomes of patients undergoing primary repair versus resection for low-grade colon injuries. A retrospective review of all patients who presented with American Association for the Surgery of Trauma grade I and II traumatic colon injuries to our Level I trauma center between 2011 and 2021 was performed. Patients were further dichotomized based on whether they underwent primary repair or resection with anastomosis. Outcome measures included length of stay data, infectious complications, and mortality. A total of 120 patients met inclusion criteria. The majority of patients (76.7%) were male, and the average age was 35.6 ± 13.1 y. Most patients also underwent primary repair (80.8%). There were no statistically significant differences between the groups in arrival physiology or in injury severity score. Length of stay data including hospital length of stay, intensive care unit length of stay, and ventilator days were similar between groups. Postoperative complications including pneumonia, surgical site infections, fascial dehiscence, the development of enterocutaneous fistulas, and unplanned returns to the operating room were also all found to be similar between groups. The group who underwent resection with anastomosis did demonstrate a higher rate of intra-abdominal abscess development (3.1% versus 26.1%, P < 0001). Mortality between both groups was not found to be statistically significant (7.2% versus 4.3%, P = 0.4) For low-grade (American Association for the Surgery of Trauma I and II) traumatic colon injuries, patients undergoing primary repair demonstrated a decreased rate of intra-abdominal abscess development when compared to patients who underwent resection with anastomosis. [ABSTRACT FROM AUTHOR]

Highlights • Numerous studies indicate that probiotics have anti-inflammatory effects. • Immune-inflammatory modulation may mediate the antidepressant effects of probiotics. • Probiotics may be more effective in depressed subgroups with elevated inflammation. • Future studies should parse out the heterogeneous effects of different probiotics. Abstract During the past decade, there has been renewed interest in the relationship between brain-based disorders, the gut microbiota, and the possible beneficial effects of probiotics. Emerging evidence suggests that modifying the composition of the gut microbiota via probiotic supplementation may be a viable adjuvant treatment option for individuals with major depressive disorder (MDD). Convergent evidence indicates that persistent low-grade inflammatory activation is associated with the diagnosis of MDD as well as the severity of depressive symptoms and probability of treatment response. The objectives of this review are to (1) evaluate the evidence supporting an anti-inflammatory effect of probiotics and (2) describe immune system modulation as a potential mechanism for the therapeutic effects of probiotics in populations with MDD. A narrative review of studies investigating the effects of probiotics on systemic inflammation was conducted. Studies were identified using PubMed/Medline, Google Scholar, and clinicaltrials.gov (from inception to November 2017) using the following search terms (and/or variants): probiotic , inflammation , gut microbiota , and depression. The available evidence suggests that probiotics should be considered a promising adjuvant treatment to reduce the inflammatory activation commonly found in MDD. Several controversial points remain to be addressed including the role of leaky gut, the role of stress exposure, and the role of blood-brain-barrier permeability. Taken together, the results of this review suggest that probiotics may be a potentially beneficial, but insufficiently studied, antidepressant treatment intervention. [ABSTRACT FROM AUTHOR]

An interview with media artist and performer the Department of Music at Brown University Joseph Butch Rovan is presented. Topics mention including the place where he grow up and how he get involved with music, his thought on the relationship between enterprise and creativity and his alternative controllers.

Background: Insulin resistance (IR) is a potential predictor of antidepressant treatment response. Aims: We assess changes in IR after antidepressant treatment and whether these changes have any effect on treatment response. Also, to see whether changes in IR mediates relationship between C-reactive protein (CRP) and antidepressant efficacy. Methods: This is a secondary analysis of an 8-week, open-label clinical trial with 95 adults experiencing a major depressive episode. Response to vortioxetine was measured using the Montgomery–Åsberg Depression Rating Scale (MADRS). Generalized estimating equation models were utilized for this intent-to-treat analysis. Results: When adjusted for age, sex, and body mass index, there was a significant increase in IR following treatment in the overall sample (p = 0.035). This finding was detected in treatment non-responders (p = 0.019), whereas it was not observed in responders (p = 0.329). Mediation analysis revealed that change in IR during treatment was responsible for change in MADRS as well as the relationship between baseline CRP and treatment response. Conclusions: Exacerbation of IR during antidepressant treatment mediated non-response. Conversely in treatment responders IR reduced. Like previous studies, baseline CRP moderated treatment response. This relationship was also mediated by changes in IR. These findings further elucidate the role of IR in terms of antidepressant response as well as potentially explain inflammation's relationship with the latter. [ABSTRACT FROM AUTHOR]

Background: Neurofibromatosis type 1 (NF1) is a common monogenic tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Haploinsufficiency of NF1 fosters a permissive tumorigenic environment through changes in signalling between cells, however the intracellular mechanisms for this tumor-promoting effect are less clear. Most primary human NF1+/- cells are a challenge to obtain, however lymphoblastoid cell lines (LCLs) have been collected from large NF1 kindreds. We hypothesized that the genetic effects of NF1-haploinsufficiency may be discerned by comparison of genome-wide transcriptional profiling in somatic, non-tumor cells (LCLs) from NF1-affected and -unaffected individuals. As a cross-species filter for heterogeneity, we compared the results from two human kindreds to whole-genome transcriptional profiling in spleen-derived B lymphocytes from age- and gender-matched Nf1+/- and wild-type mice, and used gene set enrichment analysis (GSEA), Onto-Express, Pathway-Express and MetaCore tools to identify genes perturbed in NF1- haploinsufficiency. Results: We observed moderate expression of NF1 in human LCLs and of Nf1 in CD19+ mouse B lymphocytes. Using the t test to evaluate individual transcripts, we observed modest expression differences in the transcriptome in NF1-haploinsufficient LCLs and Nf1-haploinsuffiicient mouse B lymphocytes. However, GSEA, Onto-Express, Pathway-Express and MetaCore analyses identified genes that control cell cycle, DNA replication and repair, transcription and translation, and immune response as the most perturbed in NF1-haploinsufficient conditions in both human and mouse. Conclusions: Haploinsufficiency arises when loss of one allele of a gene is sufficient to give rise to disease. Haploinsufficiency has traditionally been viewed as a passive state. Our observations of perturbed, up-regulated cell cycle and DNA repair pathways may functionally contribute to NF1-haploinsufficiency as an "active state" that ultimately promotes the loss of the wild-type allele. [ABSTRACT FROM AUTHOR]

The specialization of contemporary academia necessitates the adoption of a multidisciplinary approach to study topics that cross multiple disciplines, including the area of medical ethics. However, the nature of multidisciplinary research is limited in some regards, further requiring some researchers to use interdisciplinary and transdisciplinary approaches. The authors present as a case study a research project in bioethics that began as an interdisciplinary study and which, through the research process, moved to being a transdisciplinary study in health ethics. They outline not only this transformation but also the strengths and difficulties of transdisciplinary research in the area of ethics. [ABSTRACT FROM AUTHOR]

In response to a question on the value of replication in social science research, the author undertook a search of the literature for expert advise on the value of such an activity. Using the information gleaned and the personal experience of attempting to replicate the research of a colleague, the conclusion was drawn that replica-tion has great value but little 'real life' application in the true sense. The activity itself, regardless of the degree of precision of the replication, can have great merit in extending understanding about a method or a concept. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal Membrane Oxygenation (ECMO) is a high-risk, low-volume procedure requiring repetition, skill and multiple disciplines with fidelity of communication. Yet many barriers exist to maintain proficiency and skills with variable cost and fidelity. We designed and implemented a low-cost monthly ECMO simulation and hypothesized providers would have increased familiarity and improved teamwork. We also review some key elements of cost, fidelity and evaluation of effectiveness. Methods: A structured, 1-hour ECMO simulation was performed on a customized mannikin on a monthly basis in 2022. Qualitative surveys were administered to each member post-simulation. Answers were categorized by theme, including satisfaction of patient care, evaluation of self and team dynamics, and areas for improvement. Results: Most participants were satisfied with their ability to take care of the patient, with common themes of communication and coordination of roles. Identified areas of improvement were mostly limited to technical skills, and soft skills such as communication and teamwork. Conclusions: We designed and implemented a low-cost, monthly and multi-disciplinary ECMO simulation program with overall positive feedback and identified areas for improvement. There remains variability in cost, fidelity and evaluation of performance and retention. There may be a need to create guidelines for ECMO simulation training that can be applied at all institutions utilizing ECMO for patient care. [ABSTRACT FROM AUTHOR]

Burn depth determination is critical for patient care but is currently lacking accuracy. Recent animal studies showed that Short Wave Infrared (SWIR) imaging can distinguish between superficial and deep burns. This is a first human study correlating reflectance of multiple SWIR bands using a SWIR assessment tool (SWAT) with burn depth classifications by surgeons and histology. Burns and adjacent normal skin in 11 patients with thermal injuries were imaged with visual and narrow bands centred at 1200, 1650, 1940 and 2250 nm and biopsies were taken from select areas. Reflectance intensities for each band in 273 regions of interest (ROI) were divided by the normal skin reflectance and combined into three Reflectance Indices (RIs). In addition, burns in ROIs and biopsies were classified by five surgeons and three pathologists, respectively, as superficial partial, deep partial, or full thickness. Results show that for burn depth increase classified by the surgeons, reflectance increased at 1200 and 2250, decreased at 1940, and didn't change at 1650 nm. In contrast, all three RIs increase with burn depth and predict the deep and full depths ROIs representing operable regions (Area Under Curve >0.6507, p < 0.0001). Pathologists' classification matched surgeons' classification of burn category only in eight of 21 biopsies (38.1%), but reflectance at all bands and one RI for all deep partial and full thickness biopsies were larger than in non‐biopsy normal and superficial partial thickness ROIs (p < 0.0118). In conclusion, multi‐spectral imaging with a new SWAT is a promising approach for evaluation of burn wound depth. [ABSTRACT FROM AUTHOR]

The Parkland Trauma Index of Mortality (PTIM) is an integrated, machine learning 72-h mortality prediction model that automatically extracts and analyzes demographic, laboratory, and physiological data in polytrauma patients. We hypothesized that this validated model would perform equally as well at another level 1 trauma center. A retrospective cohort study was performed including ∼5000 adult level 1 trauma activation patients from January 2022 to September 2023. Demographics, physiologic and laboratory values were collected. First, a test set of models using PTIM clinical variables (CVs) was used as external validation, named PTIM+. Then, multiple novel mortality prediction models were developed considering all CVs designated as the Cincinnati Trauma Index of Mortality (CTIM). The statistical performance of the models was then compared. PTIM CVs were found to have similar predictive performance within the PTIM + external validation model. The highest correlating CVs used in CTIM overlapped considerably with those of the PTIM, and performance was comparable between models. Specifically, for prediction of mortality within 48 h (CTIM versus PTIM): positive prediction value was 35.6% versus 32.5%, negative prediction value was 99.6% versus 99.3%, sensitivity was 81.0% versus 82.5%, specificity was 97.3% versus 93.6%, and area under the curve was 0.98 versus 0.94. This external cohort study suggests that the variables initially identified via PTIM retain their predictive ability and are accessible in a different level 1 trauma center. This work shows that a trauma center may be able to operationalize an effective predictive model without undertaking a repeated time and resource intensive process of full variable selection. [ABSTRACT FROM AUTHOR]

• Loneliness has been associated with adverse health outcomes, but few studies have evaluated its comparative effects on distinct health outcomes. • A scoping review reveals medium to large effects of loneliness on all health outcomes, with the largest effects on mental health outcomes and overall well-being. • Healthcare providers should be adequately trained to perceive and respond to loneliness due to its strong associations with adverse health outcomes. The primary objective was to evaluate the comparative effects of loneliness on multiple distinct health outcomes. The literature was qualitatively reviewed to identify loneliness risk factors, explore mechanisms, and discuss potential evidence-based interventions for targeting loneliness. 114 identified studies were systematically reviewed and analyzed to examine for associations between loneliness (as measured by the UCLA Loneliness or de Jong Gierveld Loneliness Scales) and one or more health outcome(s). Health outcomes were broadly defined to include measures of mental health (i.e., depression, anxiety, suicidality, general mental health), general health (i.e., overall self-rated health), well-being (i.e., quality of life, life satisfaction), physical health (i.e., functional disability), sleep, and cognition. Loneliness had medium to large effects on all health outcomes, with the largest effects on mental health and overall well-being; however, this result may have been confounded by the breadth of studies exploring the association between loneliness and mental health, as opposed to other health outcomes. A significant effect of gender on the association between loneliness and cognition (i.e., more pronounced in studies with a greater proportion of males) was also observed. The adequate training of health care providers to perceive and respond to loneliness among patients should be prioritized. [ABSTRACT FROM AUTHOR]

Nationwide shelter-in-place (SIP) orders during the pandemic have had long-lasting effects, including increased rates of domestic violence and interpersonal violence. Screening for violence varies by institution, which tool is used, and when. Given increases in burn and trauma admissions over the course of the pandemic, we sought to examine trends at our institution during this time period to better guide care and anticipate system-level effects. We performed a retrospective cohort study of pediatric burn and adult burn and trauma patients at our level 1 trauma/burn center between March-May 2019 and March-May 2020. Home safety screening was performed by nursing staff using a 1-part screening questionnaire. Patients presenting before March 15, 2020, were defined as "pre-SIP; " between March 16-May 19, 2020, were "during SIP; " and those after May 19, 2020, were designated as "post-SIP." Descriptive and chi-square statistics were used. Demographic, injury patterns, and screening information were collected. Blunt trauma comprised 60% of injuries, followed by burns (30%) then penetrating injury (7%). Over the entire time period analyzed, 1822 patients had documented home safety screening; ∼2% of patients screened reported a safety concern pre-SIP, compared to 3% of patients during SIP. There were higher rates of burns and penetrating injury during SIP compared to other periods (P ≤ 0.0001). Home safety screening rates were 94%-95% pre- and during SIP, but dropped to 85% post-SIP (P < 0.0001). Home safety concerns were reported almost 2% of the time pre-SIP and 3% during SIP (P = 0.016). We noted an increase in trauma and burns during and after SIP orders, consistent with the experiences of other institutions. Implementation of a nurse-driven screening process demonstrated high compliance with appropriate referrals. The burden of burn and traumatic injury remains significant, highlighting a need for continued psychosocial screening and the provision of psychosocial support resources in the acute trauma setting. [ABSTRACT FROM AUTHOR]

Introduction: Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large clinical studies. Methods: Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the USA. Patients were included for analysis if they had a record of receiving an antibiotic concurrent with Seraph 100 treatment. Patients were excluded if there was missing information for blood flow rate. Blood samples were drawn pre- and post-filter at 1 h and 4 h after treatment initiation. These average pre- and post-filter time-concentration observations were then used to estimate antibiotic clearance in L/h (CLSeraph) due to the Seraph 100 device. Results: Of the 34 participants in the study, 17 met inclusion and exclusion criteria for the antibiotic analysis. Data were obtained for 7 antibiotics (azithromycin, cefazolin, cefepime, ceftriaxone, linezolid, piperacillin, and vancomycin) and one beta-lactamase inhibitor. Mean CLSeraph for the antibiotics investigated ranged from −0.57 to 0.47 L/h. No antibiotic had a CLSeraph statistically significant from 0. Discussion/Conclusion: The Seraph 100 did not significantly clear any measured antibiotic in clinical samples. These data give further evidence to suggest that these therapies may be safely administered to critically ill patients and will not impact concentrations of administered antibiotics. [ABSTRACT FROM AUTHOR]

• Early change in cognition was a non-significant predictor of treatment response. • Signal-to-noise ratio was low due to high heterogeneity in the cognitive data. • Future studies should stratify patients to produce more homogenous samples. • Early cognitive change may predict response in stratified MDD subpopulations. • Early change in MADRS and baseline MADRS scores were correlated with response. Antidepressant pharmacotherapy dominates current treatment in psychiatry, including treatment for major depressive disorder (MDD). However, the current trial-and-error process of medication selection contributes to treatment failure and unnecessarily exposes patients to lengthy and insufficient treatment trials. Notably, improvements in measures of cognition have been demonstrated to occur early during treatment and prior to improvements in clinical state. Cognitions have been categorized based on emotional valence (i.e., cold versus hot cognitions). Cold cognitions describe cognitive operations that are relevant to the processing of non-emotional information. The current analysis investigates whether early changes in cold cognition can predict response after 8 weeks of vortioxetine treatment in adults with MDD. This was secondary analysis of an 8-week, open-label study. Cognition was assessed at week 0 and week 2 to measure early cognitive change. Depressive symptom severity was assessed at week 0 and week 8 to measure treatment response. Eighty-one subjects were analyzed using binomial logistic regression models. Early change in cognition was a non-significant predictor of response (p = 0.845, SE = 0.599, OR = 1.124), which may have resulted from high data variability. The overall predictive accuracy of the model was low (sensitivity = 37.5%, specificity = 89.8%, PPV = 70.6%, NPV = 68.8%). Future studies should include larger samples and stratify patients based on potentially moderating variables, such as baseline cognitive impairment and occupation. Stratification would likely produce more homogenous samples, reducing the amount of variability observed for early cognitive change. [ABSTRACT FROM AUTHOR]

Background: To assess the effect of insulin resistance (IR) on treatment response to the antidepressant, vortioxetine, in patients with Major Depressive Disorder (MDD).Methods: This is a secondary analysis of an 8-week, open-label clinical trial. Ninety-five adults in a primary care setting experiencing a major depressive episode were included. Response to vortioxetine was measured using the THINC-integrated tool, Montgomery Åsberg Depression Rating Scale (MADRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Perceived Deficits Questionnaire (PDQ-5), and the Sheehan Disability Scale (SDS). Generalized estimating equation models were utilized for data analysis.Results: When adjusted for age, gender, dose, and BMI, there was a significant baseline IR by time interaction for SHAPS (p = 0.022), PDQ-5 (p = 0.037), and SDS (p = 0.013). Higher baseline IR predicted decreased early improvements in anhedonia. It also predicted poorer subjective assessments of cognition and increased functional impairment at the endpoint of treatment. For functional capacity (i.e. SDS) other covariates including severity of symptoms, illness course, other metabolic factors (e.g. cholesterol), and physical activity were included with no changes to the moderating effect of baseline IR.Limitations: This was a post-hoc analysis of a primarily non-diabetic sample. Also, only one agent was assessed.Conclusions: IR was a predictor of response to vortioxetine. This persisted after controlling for other factors including, but not limited to, BMI. These findings strengthen the link between depression and IR and may point to another novel metabolic predictor of response. These findings should be replicated using other antidepressants. [ABSTRACT FROM AUTHOR]

Background: Orthopaedic surgeons prescribe more opioid narcotics than any other surgical specialty. Proximal humerus fractures (PHF) often occur in the high-risk elderly population. The opioid epidemic has led to public policy aimed at reductions in opioid prescription. This study aimed to evaluate the impact that new legislation has had on opioid prescription patterns in patients who sustained proximal humerus fractures. Methods: A retrospective review of all patients who sustained PHF at a single academic institution from 1/1/2015–12/31/2019 was performed. A total of 762 proximal humerus fractures were identified and final analysis included 383 patients. Collected data included basic demographics and opioid prescriptions obtained through review of the electronic medical record. The North Carolina Strengthen Opioid Misuse Prevention act legislation that went into effect on July 1, 2017. Results: There was no difference in the number of pre- or postoperative opioid prescriptions provided with the new legislation. Our data showed a significant reduction in MeQs prescribed preoperatively pre-STOP act (188.1 MeQs) and post-STOP act (99.4 MeQs). There was also a significant difference in the amount of postoperative narcotics prescribed in the pre-STOP (972.6 MeQs) and post-STOP act (508.6 MeQs) groups (p < 0.01). Conclusions: With the enactment of the STOP act in North Carolina, we have seen a significant reduction in the amount of narcotic prescribed after sustaining a proximal humerus fracture preoperatively and postoperatively. This data demonstrates the impact that implementation of state-wide regulatory changes in opioid prescribing policy has had for a common orthopedic condition. [ABSTRACT FROM AUTHOR]

The article discusses the use of the evidence-based 4Ms model to improve outpatient geriatric dermatology care. Topics covered include the definitions and specific applications regardless of ethnicity, gender or comorbidities of the framework's four basic elements of matters, medication, mentation and mobility, and the encouraged collaboration of geriatricians with dermatologists in implementing the 4Ms model. Also noted are dermatologists' positive inputs on older adults' needs.

Highlights from the article: The terminal ileum was observed to pass along the cystic lesion with evidence of oral contrast extrusion from the terminal ileum into the cyst. Graph: Fig. 2Computed tomography of the abdomen and pelvis. a Contrast leak in the fistula tract between a cystic lesion (*) adjacent to the terminal ileum and abscess cavity in the space of Retzius (arrows), b fistula opening in the right groin (arrowheads) A segment of the terminal ileum and the cystic mass were removed en bloc and an abscess cavity in the space of Retzius was entered and appropriately drained.

Delays in transition to the next phase of care result in increased mortality. Prehospital literature suggests emergency medical service technicians underestimate transport times by as much as 20%. What remains unknown is clinician perception of time during the trauma resuscitation. We sought to determine if clinicians have an altered perception of time. We hypothesized that clinicians underestimate time, resulting in delay of care. Clinicians at a large level 1 trauma center completed a post-trauma activation survey on the perceived elapsed time to complete three specific resuscitation endpoints. The primary study endpoint was the time to the next phase of care, defined as leaving the trauma bay to go to the operating room, interventional radiology, computerized tomography or time of death. The data from the surveys were linked and compared with recorded videos of the resuscitations. The difference in perceived versus actual time, along with confounding variables, was used to assess the impact of perception of time on the time to the next phase of care using a stepwise multivariate linear model. There were 284 complete surveys and videos, culminating in 543 time points. The median perceived versus actual time (minutes [interquartile range]) to the next phase of care was 20 [10-25] versus 26 [19-40] (P < 0.001). Overall, clinicians underestimated time by 28%, such that if the resuscitation lasted 20 min, the clinician's perception was that 14.4 min elapsed. Differences in the perceived versus actual time in the procedure group impacted time to the next phase of care (P = 0.01). Clinicians have significant gaps in the perception of time during trauma resuscitations. This misperception occurs during procedures and correlates with an increase in the length of time to the next phase of care. [ABSTRACT FROM AUTHOR]

Current guidelines for severe rib fractures recommend neuraxial blockade in addition to multimodal pain therapies. While the guidelines for venous thromboembolism prevention recommend chemoprophylaxis, these medications must be held for neuraxial blockade placement. Erector spinae plane block (ESPB) is a newly described block for thoracic pain control. Advantages include its quick learning curve and potential for less bleeding complications. We describe the use of ESPB for rib fractures in patients on chemoprophylaxis. We hypothesize that ESPB can be performed in this patient population without holding chemoprophylaxis. This was a retrospective observational cohort study of a level 1 trauma center from 9/2016 to 12/2018. All patients with trauma with rib fractures undergoing neuraxial blockade or ESPB were included. Demographics, chemoprophylaxis and anticoagulation regimens, outcomes, and complications were collected. Nine hundred sixty-four patients with rib fracture(s) were admitted. Of these, 73 had a pain management consult. Thirteen had epidural catheters and 25 had ESPBs placed. There was no difference in demographics, injury patterns, bleeding complications, or venous thromboembolism rates among the groups. Patients with ESPB were less likely to have a dose of chemoprophylaxis held because of placement of a catheter (25% versus 100%, P < 0.00001). Three patients with ESPB were on oral anticoagulation on admission, and two were able to continue their regimen during placement. ESPB can be safely placed in patients on chemoprophylaxis. It should be considered over traditional blocks in patients with blunt chest wall trauma because of its technical ease and ability to be performed with chemoprophylaxis. • Severe rib fractures require multi-modal pain regimens which can include neuraxial blockades. • Chemoprophylaxis has to be held when performing these blockades, placing patients at increase risk for venothrombotic events. • The erector spinae plane block is a new blockade that can be safely placed while not holding chemoprophylaxis. [ABSTRACT FROM AUTHOR]

Ecological momentary assessment (EMA) for mental disorders, using application-based (app) technology capable of passive and ambient data collection, has been insufficiently evaluated and validated with rigorous, adequately-powered, high-quality studies. Herein, we sought to validate the mind.me application for the assessment of depressive symptoms in adults. Adults (ages 18–65) who self-identified as having clinically significant depressive symptoms [i.e. Patient Health Questionnaire 9 (PHQ-9) ≥ 5] utilized the mind.me app—a mobile phone technology that collects data passively and continuously, and is capable of integrating broad multimodal data [e.g., location variance (e.g. GPS), behavioural (e.g. social network activity), and communication data (e.g. SMS texting, phone calls)]. The primary outcome was predictive accuracy (i.e. convergent validity with depressive symptom measurement, as captured by the PHQ-9). 200 subjects were enrolled in the study (mean age 46 ± 12.71). The average PHQ-9 score was 12.8 ± 6.9. The predictive accuracy of the mind.me app was 0.91 ± 0.06. The sensitivity was 0.98 and the specificity was 0.93. The mind.me app was rated by 200 users as highly usable and informative to their illness. The mind.me app exhibits robust predictive accuracy in detecting depressive symptoms in adults with clinically relevant depressive symptoms. The mind.me app more specifically demonstrates convergence with the PHQ-9. [ABSTRACT FROM AUTHOR]

Background: Convergent evidence implicates gut microbiota in human health and disease. Hitherto, relatively few studies have evaluated the gut microbiota profile in individuals with bipolar disorder (BD) relative to healthy controls (HC). Methods: Fecal samples were collected from subjects (aged 18–65) meeting DSM-5-defined criteria for BD and age- and sex-matched HC without current or past history of mental or major medical disorders. Samples were sequenced using Illumina sequencing and association of specific taxa and co-occurrence of taxa with sample groups including the effect of diet was assessed using cluster analysis and analysis of communities of microorganisms (ANCOM). Nutritional composition was evaluated using the Dietary Questionnaire for Epidemiological Studies (DQES v2) Food Frequency Questionnaire. Results: Forty-six subjects were enrolled (n=23 BD, n=23 HC). Cluster analyses did not identify any significant differences between BD and HC (p=0.38). Lower microbiota diversity was observed among BD subjects relative to HC (p=0.04). A greater abundance of a Clostridiaceae OTU was observed among BD subjects when compared to HC and of Collinsella among BD-II subjects relative to BD-I. Cluster analysis revealed that neither diagnosis (p=0.38) nor diet (p=0.43) had a significant effect on overall gut microbiota composition. Limitations: This study has a small sample size and insufficient control for some potential moderating factors (e.g. psychotropic medication and smoking). Conclusion: This study suggests that individuals with BD may have a distinct gut microbiota profile compared to healthy controls, with a greater abundance of Clostridiaceae and Collinsella. These findings need to be replicated in future studies with larger sample sizes. [ABSTRACT FROM AUTHOR]

The authors regret an error in one of the extracted data points in the meta-analysis. The classification accuracy for Serretti et al. (2007) was corrected to 64% (Table 3b). The overall results before and after this correction remain directionally consistent and are summarized below (Figures 2 and 3; Table 2; results subsection 3.6). The authors apologise for any inconvenience caused. [ABSTRACT FROM AUTHOR]

Background: Major Depressive Disorder (MDD) is a common and debilitating mood disorder. Individuals with MDD are often misdiagnosed or diagnosed in an untimely manner, exacerbating existing functional impairments. Ecological momentary assessment (EMA) involves the repeated sampling of an individual's symptoms within their natural environment and has been demonstrated to assist in illness assessment and characterization. Capturing data in this way would set the stage for improved treatment outcomes and serve as a complementary resource in the management and treatment of depressive symptoms.Methods: Online databases PubMed/MedLine and PsycINFO were searched using PRISMA guidelines and combinations of the following keywords: EMA, depression, smartphone app, diagnosing, symptoms, phone, app, ecological momentary assessment, momentary assessment, data mining, unobtrusive, passive data, GPS, sensor.Results: A total of nineteen original articles were identified using our search parameters and ten articles met the inclusion criteria for full-text review. Among the ten relevant studies, three studies evaluated feasibility, seven evaluated detection, and three evaluated treatment of MDD.Limitations: Limitations include that the design of all of the studies included in this review are non-randomized. It should be noted that most of the studies included were pilot studies and/or exploratory trials lacking a control group.Conclusions: Available evidence suggests that the use of passive smartphone-based applications may lead to improved management of depressive symptoms. This review aids the creation of new EMA applications, highlights the potential of EMA usage in clinical settings and drug development, emphasizes the importance for regulation of applications in the mental health field, and provides insight into future directions. [ABSTRACT FROM AUTHOR]

Outcomes of appendectomy stratified by type of complicated appendicitis (CA) features are poorly researched, and the evidence to guide operative versus nonoperative management for CA is lacking. This study aimed to determine laparoscopic-to-open conversion risk, postoperative abscess risk, unplanned readmission risk, and length of hospital stay (LOS) associated with appendectomy in patients with perforated appendicitis without abscess (PA) and perforated appendicitis with abscess (PAWA) compared with a control cohort of nonperforated appendicitis (NPA). The 2016-2017 National Surgical Quality Improvement Program Appendectomy-targeted database identified 12,537 (76.1%) patients with NPA, 2142 (13.0%) patients with PA, and 1799 (10.9%) patients with PAWA. Chi-squared analysis and analysis of variance were used to compare categorical and continuous variables. Binary logistic and linear regression models were used to compare risk-adjusted outcomes. Compared with NPA, PA and PAWA had higher rates of conversion (0.8% versus 4.9% and 6.5%, respectively; P < 0.001), postoperative abscess requiring intervention (0.6% versus 4.8% and 7.0%, respectively; P < 0.001), readmission (2.8% versus 7.7% and 7.6%, respectively; P < 0.001), and longer median LOS (1 day versus 2 days and 2 days, respectively; P < 0.001). PA and PAWA were associated with increased odds of postoperative abscess (odds ratio [OR]: 7.18, 95% confidence interval [CI]: 5.2-9.8 and OR: 9.94, 95% CI: 7.3-13.5, respectively), readmission (OR: 2.70, 95% CI: 2.1-3.3 and OR: 2.66, 95% CI: 2.2-3.3, respectively), and conversion (OR: 5.51, 95% CI: 4.0-7.5 and OR: 7.43, 95% CI: 5.5-10.1, respectively). PA was associated with an increased LOS of 1.7 days and PAWA with 1.9 days of LOS (95% CI: 1.5-1.8 and 1.7-2.1, respectively). Individual features of CA were independently associated with outcomes. Further research is needed to determine if surgical management is superior to nonoperative management for CA. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine whether changes in physical activity predicted reductions in depression during the 8 weeks of antidepressant treatment with vortioxetine.Methods: One hundred individuals were recruited for the (THINC-it ®)-sensitivity to change study. Self-reported moderate-to-vigorous physical activity (MVPA) and depression severity were assessed at baseline, week 4 and week 8. Linear mixed model analyses were performed to examine whether increases in MVPA were associated with reduction in depression severity over the course of treatment and hierarchical logistic regression analyses were performed to assess whether treatment response (responders vs. non-responders) at week 8 was predicted by early change in physical activity (MVPA at week 4), after controlling for individuals' demographics (sex, age, race, education level, BMI) and baseline MVPA and depression severity.Results: After controlling for individuals' demographics, a significant increase in MVPA predicted reduction in depression severity, β = -2.06, 95% CI -3.18, -0.94, p <0.001. Individuals with more physical activity at week 4 relative to baseline had higher odds of treatment response at endpoint, OR 1.97, 95% CI 1.11 - 3.48, p <0.05. Twenty-one percent of total variance of depression severity was explained by change in MVPA.Conclusions: The study suggests that early increases in physical activity may be a behavioral marker of antidepressant treatment response. The inclusion of physical activity measures in future clinical treatment trials of depression is recommended to explore whether changes in physical activity mediate or moderate reductions in depression severity associated with the primary treatment. [ABSTRACT FROM AUTHOR]

Background: Anhedonia and abnormalities in reward behavior are core features of major depressive disorder (MDD). Convergent evidence indicates that overweight/obesity (OW), a highly prevalent condition in MDD, is independently associated with reward disturbances. We therefore aimed to investigate the moderating effect of OW on the willingness to expend efforts for reward in individuals with MDD and healthy controls (HC).Methods: Forty-one adults (HC n = 20, MDD n = 21) completed the Effort Expenditure for Rewards Task (EEfRT), clinical and cognitive measures. Anthropometric parameters were assessed in all participants, and an additional evaluation of laboratorial parameters were conducted solely on those with MDD. Individuals with MDD were all on vortioxetine monotherapy (10-20 mg/day).Results: Interactions between reward magnitude, group and OW were observed (χ2 = 9.192, p = 0.010); the OW-MDD group chose the hard task significantly less than normal weight (NW)-HC (p = 0.033) and OW-HC (p = 0.034), whereas there were no differences between NW-MDD and HCs. Within individuals with MDD, the proportion of hard task choices was more strongly correlated with body mass index (BMI) (r = -0.456, p = 0.043) and insulin resistance (HOMA2-IR) (r = -0.467, p = 0.038), than with depressive symptoms (r = 0.290, p = 0.214).Conclusions: OW significantly moderated the association between MDD and willingness to make efforts for rewards. These findings offer novel evidence on the potential role of metabolic factors on the basis of anhedonia, and for the heuristic models proposing a pathophysiological connection between mood and metabolic disorders. [ABSTRACT FROM AUTHOR]

Although direct‐acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection are highly efficacious and safe, treatment initiation is often limited in patients with neuropsychiatric disorders due to concerns over reduced treatment adherence and drug–drug interactions. Here, we report adherence, efficacy, safety and patient‐reported outcomes (PROs) from an integrated analysis of registrational studies using the pangenotypic DAA regimen of glecaprevir and pibrentasvir (G/P). Patients with chronic HCV genotypes 1‐6 infection with compensated liver disease (with or without cirrhosis) receiving G/P for 8, 12 or 16 weeks were included in this analysis. Patients were classified as having a psychiatric disorder based on medical history and/or co‐medications. Primary analyses assessed treatment adherence, efficacy (sustained virologic response at post‐treatment week 12; SVR12), safety and PROs. Among 2522 patients receiving G/P, 789 (31%) had a psychiatric disorder with the most common diagnoses being depression (64%; 506/789) and anxiety disorders (27%; 216/789). Treatment adherence was comparably high (>95%) in patients with and without psychiatric disorders. SVR12 rates were 97.3% (768/789; 95% CI = 96.2‐98.5) and 97.5% (1689/1733; 95% CI = 96.7‐98.2) in patients with and without psychiatric disorders, respectively. Among patients with psychiatric disorders, SVR12 rates remained >96% by individual psychiatric diagnoses and co‐medication classes. Overall, most adverse events (AEs) were mild‐to‐moderate in severity with serious AEs and AEs leading to G/P discontinuation occurring at similarly low rates in both patient populations. In conclusion, G/P treatment was highly efficacious, well‐tolerated and demonstrated high adherence rates in patients with chronic HCV infection and psychiatric disorders. [ABSTRACT FROM AUTHOR]

Anhedonia is defined as a diminished ability to experience interest or pleasure, and is a critical psychopathological dimension of major depressive disorder (MDD). The purpose of the current systematic review is to evaluate the therapeutic efficacy of pharmacological treatments on measures of anhedonia in adults with MDD. Electronic databases Cochrane Library (CENTRAL), Ovid MEDLINE, PubMed, PsycINFO, and Google Scholar were searched from inception to June 1, 2018 for longitudinal studies utilizing pharmacotherapy for the treatment of anhedonia in patients with MDD. A total of 17 eligible studies were identified (i.e., evaluated the effects of pharmacotherapy on a measure of anhedonia). Among the identified studies, the efficacy of 14 different pharmacotherapies on measures of anhedonia were evaluated, including melatonergic agents (i.e. agomelatine), monoaminergic agents (i.e. moclobemide, clomipramine, bupropion, venlafaxine, fluoxetine, amitifadine and levomilnacipran, escitalopram, and sertraline), glutamatergic agents (i.e., ketamine and riluzole), stimulants (i.e., methylphenidate), and psychedelics (i.e., psilocybin). Based on the available evidence, most antidepressants demonstrated beneficial effects on measures of anhedonia as well as the other depressive symptoms. Only escitalopram/riluzole combination treatment was ineffective in treating symptoms of anhedonia in MDD. Continued research is warranted to further support the efficacy of mechanistically-distinct antidepressants in treating symptoms of anhedonia in MDD. Future research should also aim to parse out the heterogeneous effects of different pharmacotherapies on anhedonic symptoms. • Majority of antidepressants do not show pronounced collinear improvements in anhedonia and other depressive symptoms. • Therapies targeting melatonergic receptors and circadian rhythm imbalances are more direct targets for treating anhedonia. • Ketamine may be faster acting of anti-anhedonia due to direct effect on mitochondrial energy metabolism. [ABSTRACT FROM AUTHOR]

Highlights • Based on the HILIC LC-MS platform, our pilot study analyzed the association between the levels of five N -acetyl derivatives and schizophrenia. • Higher levels of N -acetyl-glutamine were found in first-episode patients with schizophrenia compared to HC in our study. • Decreased N6 -acetyl- L -lysine in first-episode patients with schizophrenia were found compared to HC. • The findings may prove useful in identifying novel disease markers and/or drug target molecules in schizophrenia. Abstract N- acetyl group metabolites are a general class of endogenous compounds characterized by a conjugated system consisting of an acetyl group and nitrogen moiety. The aim of our exploratory pilot case-control study is to compare the levels of five N- acetyl derivatives (i.e., N- acetyl-glutamine, N- acetyl-ornithine, N 6-acetyl- L -lysine, N- acetyl-putrescine, and N- acetyl-galactosamine) in serum samples between individuals with first-episode schizophrenia and healthy controls (HC). A 1:2 age- and sex- matched pilot case-control study was performed, involving 30 cases of first-episode schizophrenia and 60 HC aged between 18 and 40 years old. The serum samples containing these N- acetyl derivatives from (first-episode patients with schizophrenia and HC were measured using liquid chromatography-tandem mass spectrometry (LC-MS). Results indicated that higher levels of N- acetyl-glutamine and lower levels of N 6-acetyl- L -lysine may have a significant association with schizophrenia after adjusting for age, sex and BMI. N- acetyl-putrescine was elevated among subjects with first-episode schizophrenia when compared to HC, suggesting it as a predictor for schizophrenia onset. Further exploration of the mechanisms of N- acetyl group metabolites with respect to schizophrenia is warranted and may be useful for identifying novel disease markers and/or drug target molecules in schizophrenia. [ABSTRACT FROM AUTHOR]

Poison frogs acquire chemical defenses from the environment for protection against potential predators. These defensive chemicals are lipophilic alkaloids that are sequestered by poison frogs from dietary arthropods and stored in skin glands. Despite decades of research focusing on identifying poison frog alkaloids, we know relatively little about how environmental variation and subsequent arthropod availability impacts alkaloid loads in poison frogs. We investigated how seasonal environmental variation influences poison frog chemical profiles through changes in the diet of the Climbing Mantella (Mantella laevigata). We collected M. laevigata females on the Nosy Mangabe island reserve in Madagascar during the wet and dry seasons and tested the hypothesis that seasonal differences in rainfall is associated with changes in diet composition and skin alkaloid profiles of M. laevigata. The arthropod diet of each frog was characterized into five groups (i.e. ants, termites, mites, insect larvae, or ‘other’) using visual identification and cytochrome oxidase 1 DNA barcoding. We found that frog diet differed between the wet and dry seasons, where frogs had a more diverse diet in the wet season and consumed a higher percentage of ants in the dry season. To determine if seasonality was associated with variation in frog defensive chemical composition, we used gas chromatography / mass spectrometry to quantify alkaloids from individual skin samples. Although the assortment of identified alkaloids was similar across seasons, we detected significant differences in the abundance of certain alkaloids, which we hypothesize reflects seasonal variation in the diet of M. laevigata. We suggest that these variations could originate from seasonal changes in either arthropod leaf litter composition or changes in frog behavioral patterns. Although additional studies are needed to understand the consequences of long-term environmental shifts, this work suggests that alkaloid profiles are relatively robust against short-term environmental perturbations. [ABSTRACT FROM AUTHOR]

Background: No previous study has comprehensively reviewed the application of machine learning algorithms in mood disorders populations. Herein, we qualitatively and quantitatively evaluate previous studies of machine learning-devised models that predict therapeutic outcomes in mood disorders populations.Methods: We searched Ovid MEDLINE/PubMed from inception to February 8, 2018 for relevant studies that included adults with bipolar or unipolar depression; assessed therapeutic outcomes with a pharmacological, neuromodulatory, or manual-based psychotherapeutic intervention for depression; applied a machine learning algorithm; and reported predictors of therapeutic response. A random-effects meta-analysis of proportions and meta-regression analyses were conducted.Results: We identified 639 records: 75 full-text publications were assessed for eligibility; 26 studies (n=17,499) and 20 studies (n=6325) were included in qualitative and quantitative review, respectively. Classification algorithms were able to predict therapeutic outcomes with an overall accuracy of 0.82 (95% confidence interval [CI] of [0.77, 0.87]). Pooled estimates of classification accuracy were significantly greater (p < 0.01) in models informed by multiple data types (e.g., composite of phenomenological patient features and neuroimaging or peripheral gene expression data; pooled proportion [95% CI] = 0.93[0.86, 0.97]) when compared to models with lower-dimension data types (pooledproportion=0.68[0.62,0.74]to0.85[0.81,0.88]).Limitations: Most studies were retrospective; differences in machine learning algorithms and their implementation (e.g., cross-validation, hyperparameter tuning); cannot infer importance of individual variables fed into learning algorithm.Conclusions: Machine learning algorithms provide a powerful conceptual and analytic framework capable of integrating multiple data types and sources. An integrative approach may more effectively model neurobiological components as functional modules of pathophysiology embedded within the complex, social dynamics that influence the phenomenology of mental disorders. [ABSTRACT FROM AUTHOR]

Introduction: Chronic hepatitis C (CHC) infection is associated with extrahepatic manifestations (EHMs) which can affect renal, cardiovascular and other comorbidities. The effect of CHC treatment with short-duration regimens on these EHMs is not well defined. Hence, we examined longitudinal estimated glomerular filtration rate (eGFR), triglycerides and glucose values to assess the impact of short-duration CHC therapy on renal, cardiovascular and metabolic diseases, respectively.Methods: We conducted analyses of all patients without cirrhosis treated with glecaprevir and pibrentasvir (G/P) for 8 weeks in two phase 3 clinical trials. In addition, one phase 3 trial was carried out to explore the effects of treatment on renal EHMs in patients with advanced renal impairment at baseline. As a sensitivity analysis, we included all CHC patients treated with G/P for 8 or 12 weeks enrolled across five phase 3 trials. Adjusting for baseline demographics and clinical properties via mixed regression models enabled evaluation of changes in EHMs through end of treatment.Results: G/P treatment for 8 weeks resulted in statistically significant declines in triglycerides (− 28.6 mg/dl) and glucose (− 11.2 mg/dl), while there was no statistically significant decline in eGFR. Biomarker improvements were greatest among patients with elevated triglycerides and elevated glucose at baseline. Similar effects were observed across all patients treated with G/P for 8 or 12 weeks.Conclusion: Short-duration treatment with G/P resulted in stable renal function and improvements in cardiovascular and metabolic EHM markers, especially in patients with severe EHMs at baseline.Funding: AbbVie Inc. [ABSTRACT FROM AUTHOR]

This study (registered with PROSPERO, CRD42018085967) compares the efficacy (i.e. pro‐cognitive effects) and acceptability of antidiabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials comparing antidiabetic agents with placebo and/or another active antidiabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4855) evaluating the effects of 6 different antidiabetic drugs (i.e. intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with antidiabetic agents compared with placebo. Pioglitazone 15 to 30 mg demonstrated the greatest efficacy compared to placebo in network meta‐analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro‐cognitive class effect of antidiabetic agents in AD/MCI. Other antidiabetic agents should also be investigated in future studies. [ABSTRACT FROM AUTHOR]

Objectives: To explore differences in adipokine levels (i.e., leptin and adiponectin levels) between adults with Major Depressive Disorder (MDD) and healthy controls (HC), and to discuss the possible role of adipokine regulation in the development and progression of MDD.Methods: A systematic review and meta-analysis were conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic search was conducted for all English and Chinese peer-reviewed articles from inception to November 2017. A random effects model was used to calculate the standardized mean difference (SMD) of leptin and/or adiponectin levels in subjects diagnosed with MDD versus HC within a 95% confidence interval (CI).Results: Thirty-three studies were included in this meta-analysis. In total, 4,372 (52.3%) subjects with MDD and 3,984 (47.7%) HC were compared. We identified significant lower adiponectin levels in MDD compared to HC with a small effect size (ES) (SMD = -0.25; 95% CI: -0.48, -0.02; P < 0.001). However, no significant difference was observed in leptin levels between MDD subjects and HC (SMD = 0.13; 95% CI: -0.06, 0.31; P = 0.170). The heterogeneity in the results of our meta-analysis could not be completely explained by dividing subjects into subgroups. Results from subgroup analyses suggested that studies involving samples with BMI ≥ 25 had lower adiponectin levels in subjects with MDD compared to HC, and older age samples (i.e., age ≥ 40) with BMI ≥ 25 had both higher leptin levels and lower adiponectin levels in MDD subjects as compared to HC.Limitations: The heterogeneity of included studies, small sample sizes, and potential publication bias were significant limitations.Conclusions: The current systematic review and meta-analysis indicated that lower adiponectin levels may be associated with MDD. Moreover, the results suggest that males expressing lower adiponectin and leptin levels have an increased likelihood of developing MDD. Future studies should aim to investigate the manifestation of depressive phenotypes in older, obese populations with altered metabolic profiles resulting from adipokine dysregulation. The review has been registered with PROSPERO (registration number CRD42018082733). [ABSTRACT FROM AUTHOR]