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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]

Background: Early enoxaparin 30 mg BID administration at 24 h post-injury has been demonstrated in patients with traumatic brain injury (TBI). However this dose can also yield subtherapeutic anti-Xa levels in 30–50% of trauma patients, suggesting that larger doses may be required for adequate prophylaxis against venous thromboembolism (VTE). The safety of enoxaparin 40 mg BID in trauma patients has previously been shown – however, these studies have largely excluded TBI patients. Therefore, we sought to demonstrate the safety of early enoxaparin 40 mg BID in a low-risk group of TBI patients. Methods: A retrospective review of TBI patients at a Level 1 trauma center was performed. Patients with stable computed tomography (CT) of the head at 6 to 24 h post-injury who received enoxaparin 40 mg BID were included and serial GCS evaluations to identify possible clinical complications. To evaluate the safety of this dosing regimen, data was then compared to patients from our institution with similar TBI profiles who had received 5,000 units (U) of subcutaneous heparin (SQH) prophylaxis. Results: 199 TBI patients were identified over a nine month period, 40/199 (19.7%) received DVT prophylaxis after traumatic injury. Of these 40, 19 (47.5%) received enoxaparin 40 mg BID and 21 (52.5%) received 5,000U of SQH. Low risk TBI patients who were either given enoxaparin (n = 7) or SQH (n = 4), demonstrated no clinical decline in mental status during their inpatient stay. Conclusion: Prior studies have demonstrated that enoxaparin 40 mg BID dosing is superior to traditional VTE prophylaxis in trauma patients. However, TBI patients are often excluded from this dosing due to concern for progression. Our study showed no clinical decline in mental status in a small cohort of low-risk TBI patients who received enoxaparin 40 mg BID. [ABSTRACT FROM AUTHOR]

Background: Positron emission tomography (PET) is the clinical gold standard for quantifying myocardial blood flow (MBF). Pericoronary adipose tissue (PCAT) attenuation may detect vascular inflammation indirectly. We examined the relationship between MBF by PET and plaque burden and PCAT on coronary CT angiography (CCTA). Methods: This post hoc analysis of the PACIFIC trial included 208 patients with suspected coronary artery disease (CAD) who underwent [15O]H2O PET and CCTA. Low-attenuation plaque (LAP, < 30HU), non-calcified plaque (NCP), and PCAT attenuation were measured by CCTA. Results: In 582 vessels, 211 (36.3%) had impaired per-vessel hyperemic MBF (≤ 2.30 mL/min/g). In multivariable analysis, LAP burden was independently and consistently associated with impaired hyperemic MBF (P = 0.016); over NCP burden (P = 0.997). Addition of LAP burden improved predictive performance for impaired hyperemic MBF from a model with CAD severity and calcified plaque burden (P < 0.001). There was no correlation between PCAT attenuation and hyperemic MBF (r = − 0.11), and PCAT attenuation was not associated with impaired hyperemic MBF in univariable or multivariable analysis of all vessels (P > 0.1). Conclusion: In patients with stable CAD, LAP burden was independently associated with impaired hyperemic MBF and a stronger predictor of impaired hyperemic MBF than NCP burden. There was no association between PCAT attenuation and hyperemic MBF. [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]

Background: Flexible ligamentous fixation has increased in popularity for the treatment of ligamentous Lisfranc injury, but the optimal fixation strategy is unclear. Purpose: To review the biomechanical, clinical, and radiographic results of ligamentous Lisfranc injuries treated with flexible fixation. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic literature review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed/Medline and Google Scholar literature databases were queried for clinical and biomechanical (cadaveric) studies relating to flexible fixation of ligamentous Lisfranc injury. Outcomes of interest included patient-reported outcome scores, clinical/biomechanical results, radiographic alignment, and return to activity. Where appropriate, meta-analysis of the postoperative outcomes was performed. Results: Of the 34 initial studies, 14 articles (243 feet) were included in the analysis. In the 11 clinical studies (216 patients), the mean postoperative American Orthopaedic Foot & Ankle Society score was 90.1 (n = 150; 6 studies) and the mean visual analog scale score was 1.5 (n = 137; 5 studies). The rate of return to activity was 100% (n = 35; 5 studies), and 100% of patients maintained radiographic alignment postoperatively (n = 62; 6 studies). No complications or subsequent hardware removals were reported. Of the 3 biomechanical studies (27 feet), 1 study found significantly greater change in diastasis under axial load between intact and postfixation ligaments with suture button versus screw fixation (+1.1 vs –0.1 mm; P <.05), another found no difference in the decrease in diastasis under axial load between the injured state and screw or suture button fixation (1.2 vs 1.0 mm; P =.5), and the third found no difference in displacement between intact and either screw or suture button fixation under either axial (intact vs screw: 1.0 vs 2.0 mm, P =.1; intact vs suture button: 0.6 vs 1.8 mm, P =.1) or abduction (intact vs screw: 1.5 vs 1.1 mm, P =.5; intact vs suture button: 1.3 vs 2.1 mm, P =.1) load. Conclusion: Flexible fixation use in the treatment of ligamentous Lisfranc injury was found to have significant potential as a fixation option, as demonstrated by excellent clinical results. Biomechanical evidence was inconclusive but suggested a trend toward decreased diastasis in specimens fixed with screws compared with suture buttons. [ABSTRACT FROM AUTHOR]

Background: Psychological distress after orthopaedic surgery can lead to worse outcomes, including higher levels of disability and pain and lower quality of life. The 10-item Optimal Screening for Prediction for Referral and Outcome–Yellow Flag (OSPRO-YF) survey screens for multiple psychological constructs relevant to recovery from orthopaedic injury and may be useful to preoperatively identify patients who may require further psychological assessment and possible intervention after surgery. Purpose/Hypothesis: To determine the association between the OSPRO-YF and physiological patient-reported outcomes (PROs). It was hypothesized that higher OSPRO-YF scores (indicating worse psychological distress) would be associated with worse PRO scores at time of return to sport. Study Design: Case series; Level of evidence, 4. Methods: This study evaluated 107 patients at a single, academic health center who were assessed at a sports orthopaedics clinic and ultimately treated surgically for injuries to the knee, shoulder, foot, or ankle. Preoperatively, patients completed the OSPRO-YF survey as well as the following PRO measures: Patient-Reported Outcomes Measurement Information System (PROMIS), Single Assessment Numeric Evaluation, numeric rating scale for pain; American Shoulder and Elbow Surgeons standardized shoulder assessment form for patients with shoulder injuries, the International Knee Documentation Committee score (for patients with knee injuries), and the Foot and Ankle Ability Measure (FAAM; for patients with foot or ankle injuries). At the time of anticipated full recovery and/or return to sport, patients again completed the same PRO surveys. Multivariable regression was used to evaluate the association between total OSPRO-YF score at baseline and PRO scores at the time of functional recovery. Results: The baseline OSPRO-YF score predicted postoperative PROMIS Physical Function and FAAM Sports scores only. A 1-unit increase in the OSPRO-YF was associated with a 0.55-point reduction in PROMIS Physical Function (95% CI, –1.05 to –0.04; P =.033) indicating worse outcomes. Among patients who underwent ankle surgery, a 1-unit increase in OSPRO-YF was associated with a 6.45-point reduction in FAAM Sports (95% CI, –12.0 to –0.87; P =.023). Conclusion: The study findings demonstrated that the OSPRO-YF survey predicts certain long-term PRO scores at the time of expected return to sport, independent of baseline scores. [ABSTRACT FROM AUTHOR]

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]

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.

Purpose: Surgical trainees are exposed to less procedures with increasing need for simulation. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has become increasingly implemented for hemorrhage control, yet most courses are catered to faculty level with little data on trainees. We propose that routine training in this critical procedure will improve trainee performance over time. Methods: This is a prospective, observational study at a level I trauma center involving a monthly trauma procedural program. Early in the month, trainees received hands-on REBOA training; at the end, trainees underwent standardized, class-based evaluation on a perfused trainer. Score percentages were recorded (0–100%). Endpoints included early, mid and late performance (2–12 months). Paired T-test and Pearson's coefficient were used to evaluate differences and strength of association between time between training and performance. Results: 25 trainees participated with 5 and 11 repeat learners in the PGY-2 and PGY-3 classes, respectively. Median early performance score was 62.5% (IQR 56–81) for PGY-2s and 91.6% (IQR 75–100) in PGY-3s. Pearson's coefficient between time between and training and score demonstrated a weak correlation in the PGY-2s (r2 = − 0.13), but was more pronounced in the PGY-3s (r2 = − 0.44) with an inflection point at 5 months. Conclusions: Routine REBOA training in trainees is associated with improvement in performance within a short period of time. Skill degradation was most pronounced in trainees who did not receive training for more than 5 months. Trainees can be successfully trained in REBOA; however, this should be done at shorter intervals to prevent skill degradation. [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]

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]

With increasing demand for large-scale data and effective, wide-spread action, conservation volunteers can play an important role in tackling the global biodiversity crisis. Cost-cutting pragmatism aside, the recruitment of volunteers into diverse roles within conservation organisations also responds to growing public concern for the environment and demand for 'meaningful' engagement in people's pastime. Here we argue that this auspicious premise of a win-win transaction fails to acknowledge a range of emerging ethical issues regarding the management of unpaid workers. This lack of critical examination frustrates the development of solutions that are effective for conservation and fair to volunteers. We focus our attention on three archetypal cases—citizen science, voluntourism and unpaid internships—to highlight the complex and value-laden trade-offs that need to be negotiated to ethically manage unpaid work in conservation. We identify opportunities to redress the balance between volunteer needs and conservation goals. Ultimately, we hope to stimulate further, more open debate on the effective and fair use of the available labour force in conservation. [ABSTRACT FROM AUTHOR]

Background: Herein, we sought to determine the sensitivity to change in cognitive function, as measured by the THINC-it tool, in a sample of adults with major depressive disorder (MDD) receiving standardized antidepressant therapy. Methods: Adults meeting the DSM-5 criteria for MDD with at least moderate depressive symptom severity [ i.e. , Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥ 20] were treated with open-label vortioxetine (10–20 mg/day, flexibly-dosed) for 8 weeks. The previously validated THINC-it tool was the primary dependent measure. The THINC-it tool was validated against the paper and pencil version of the Digit Symbol Substitution Test (DSST) and the Trails Making Test B (TMTB). Results: After 8 weeks of treatment, adults with MDD exhibited improvement in cognitive function relative to healthy controls (e.g. , processing speed) (p = 0.031). A subdomain measure of working memory (i.e. , symbol check; SC) exhibited significant improvement at Weeks 2 and 8 in latency (p = 0.032), SC accuracy (p = 0.046), and objective z-score (p = 0.001) independent of depressive symptoms. A linear regression analysis determined that the THINC-it tool measures of processing speed, as well as executive function were significantly associated with changes observed on the pencil and paper version the Digit Symbol Substitution Test (DSST) (p = 0.002) and in Trails Making Test B (TMTB) (p = 0.003), respectively. Conclusion: The THINC-it tool demonstrates sensitivity to change in adults with MDD and is highly correlated with improvements on pencil and paper versions of DSST and TMTB. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03053362. [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]

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]

Background: Anhedonia is a common, persistent, and disabling phenomenon in treated adults with Major Depressive Disorder (MDD). Hitherto, relatively few antidepressant agents have been evaluated with respect to their effect on anhedonia in MDD. Methods: This is a post-hoc analysis of a primary study that sought to evaluate the sensitivity to change of the THINC-integrated tool (THINC-it) in MDD (ClinicalTrials.gov Identifier: NCT03053362). Adults meeting DSM-5 criteria for MDD with at least moderate depressive symptom severity [i.e., Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥20] were eligible. Subjects were recruited between October 2017 and August 2018 in Toronto, Ontario at the Brain and Cognition Discovery Foundation. All subjects received open-label vortioxetine (10–20 mg/day, flexibly-dosed) for 8 weeks. Herein, the primary outcome of interest was the change from baseline to endpoint in the Snaith-Hamilton Pleasure Scale (SHAPS) total score, as well as the MADRS anhedonia factor. The mediational effects of improvements in anhedonia on general function and quality of life, as measured by the Sheehan Disability Scale (SDS) and the 5-Item World Health Organization Well-Being Index (WHO-5), were secondarily assessed. Results: A total of 100 subjects with MDD were enrolled in the primary study and began treatment with vortioxetine. Vortioxetine significantly improved anhedonia as evidenced by significant baseline to endpoint improvements in SHAPS and MADRS anhedonia factor scores (p < 0.0001). Improvements in the SHAPS and the MADRS anhedonia factor correlated with improvements in general function (i.e., SDS) and quality of life (i.e., WHO-5) (p < 0.0001). Notably, improvements in anhedonia were found to mediate the association between improvements in overall depressive symptom severity (i.e., MADRS total score) and social functioning (i.e., social life component of the SDS) (p = 0.026). Conclusion: The unmet need in depression is to improve patient functioning and other patient-reported outcomes (e.g., quality of life). Antidepressant interventions capable of attenuating anhedonia as well as cognitive dysfunction in MDD may help in this regard, as improvement in these domains have been associated with improvement in psychosocial function and quality of life. [ABSTRACT FROM AUTHOR]

Convergent evidence demonstrates that immune dysfunction (e.g. chronic low-grade inflammatory activation) plays an important role in the development and progression of mood disorders. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway is a pleiotropic cellular cascade that transduces numerous signals, including signals from the release of cytokines and growth factors. The JAK/STAT signaling pathway is involved in mediating several functions of the central nervous system, including neurogenesis, synaptic plasticity, gliogenesis, and microglial activation, all of which have been implicated in the pathophysiology of mood disorders. In addition, the antidepressant actions of current treatments have been shown to be mediated by JAK/STAT-dependent mechanisms. To date, two JAK inhibitors (JAKinibs) have been approved by the U.S. Food and Drug Administration and are primarily indicated for the treatment of inflammatory conditions such as rheumatoid arthritis. Indirect evidence from studies in populations with inflammatory conditions indicates that JAKinibs significantly improve measures of mood and quality of life. There is also direct evidence from studies in populations with depressive disorders, suggesting that JAK/STAT pathways may be involved in the pathophysiology of depression and that the inhibition of specific JAK/STAT pathways (i.e. via JAKinibs) may be a promising novel treatment for depressive disorders. [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]

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]

Pneumatosis intestinalis and gastric pneumatosis are rare, but potentially morbid conditions in the burn-injured patient. They present a pediatric patient with severe scald injuries and isolated gastric pneumatosis who was successfully treated with a multidisciplinary approach and nonoperative management. [ABSTRACT FROM AUTHOR]

Learning objectives: After participating in this activity, learners should be better able to: • Characterize cognitive dysfunction in patients with major depressive disorder. • Evaluate approaches to treating cognitive dysfunction in patients with major depressive disorder. Cognitive dysfunction is a core psychopathological domain in major depressive disorder (MDD) and is no longer considered to be a pseudo-specific phenomenon. Cognitive dysfunction in MDD is a principal determinant of patient-reported outcomes, which, hitherto, have been insufficiently targeted with existing multimodal treatments for MDD. The neural structures and substructures subserving cognitive function in MDD overlap with, yet are discrete from, those subserving emotion processing and affect regulation. Several modifiable factors influence the presence and extent of cognitive dysfunction in MDD, including clinical features (e.g., episode frequency and illness duration), comorbidity (e.g., obesity and diabetes), and iatrogenic artefact. Screening and measurement tools that comport with the clinical ecosystem are available to detect and measure cognitive function in MDD. Notwithstanding the availability of select antidepressants capable of exerting procognitive effects, most have not been sufficiently studied or rigorously evaluated. Promising pharmacological avenues, as well as psychosocial, behavioral, chronotherapeutic, and complementary alternative approaches, are currently being investigated. [ABSTRACT FROM AUTHOR]

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.