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Solitary fibrous tumours (SFTs) are rare neoplasms derived from mesenchymal cell lines. They are often asymptomatic, follow an indolent growth pattern and are more often benign than malignant. Here, we present a case of a very large, asymptomatic mediastinal SFT in an otherwise healthy man. A 67-year-old Irish man was referred for workup of an asymptomatic murmur. Auscultation of the lung fields revealed diminished breath sounds on the right side. Chest X-ray identified a 20 cm mass localised within the thorax. CT of the thorax confirmed a pleural based, solid lesion with no local invasion. CT-guided core biopsies were reported as consistent with SFT. Primary excision of the lesion was undertaken via median sternotomy. Histological examination confirmed a diagnosis of SFT. The patient remains well at this time. Primary excisive surgery is a safe and effective treatment modality for SFTs.

OBJECTIVE: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth.METHODS: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer.RESULTS: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001).CONCLUSION: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.

Spinocerebellar ataxia Type 3 (SCA3), the most common dominantly inherited ataxia, is a polyglutamine neurodegenerative disease for which there is no disease-modifying therapy. The polyglutamine-encoding CAG repeat expansion in theATXN3gene results in expression of a mutant form of the ATXN3 protein, a deubiquitinase that causes selective neurodegeneration despite being widely expressed. The mechanisms driving neurodegeneration in SCA3 are unclear. Research to date, however, has focused almost exclusively on neurons. Here, using equal male and female age-matched transgenic mice expressing full-length human mutantATXN3, we identified early and robust transcriptional changes in selectively vulnerable brain regions that implicate oligodendrocytes in disease pathogenesis. We mapped transcriptional changes across early, mid, and late stages of disease in two selectively vulnerable brain regions: the cerebellum and brainstem. The most significant disease-associated module through weighted gene coexpression network analysis revealed dysfunction in SCA3 oligodendrocyte maturation. These results reflect a toxic gain-of-function mechanism, asATXN3KO mice do not exhibit any impairments in oligodendrocyte maturation. Genetic crosses to reporter mice revealed a marked reduction in mature oligodendrocytes in SCA3-disease vulnerable brain regions, and ultrastructural microscopy confirmed abnormalities in axonal myelination. Further study of isolated oligodendrocyte precursor cells from SCA3 mice established that this impairment in oligodendrocyte maturation is a cell-autonomous process. We conclude that SCA3 is not simply a disease of neurons, and the search for therapeutic strategies and disease biomarkers will need to account for non-neuronal involvement in SCA3 pathogenesis.SIGNIFICANCE STATEMENTDespite advances in spinocerebellar ataxia Type 3 (SCA3) disease understanding, much remains unknown about how the disease gene causes brain dysfunction ultimately leading to cell death. We completed a longitudinal transcriptomic analysis of vulnerable brain regions in SCA3 mice to define the earliest and most robust changes across disease progression. Through gene network analyses followed up with biochemical and histologic studies in SCA3 mice, we provide evidence for severe dysfunction in oligodendrocyte maturation early in SCA3 pathogenesis. Our results advance understanding of SCA3 disease mechanisms, identify additional routes for therapeutic intervention, and may provide broader insight into polyglutamine diseases beyond SCA3.

Background Up to 70% of patients with ANCA-associated vasculitis (AAV) develop GN, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (usCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. Methods We assessed a diagnostic-grade usCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and ten controls. Results We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, usCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic AKI. usCD163's specificity declined in patients with AAV who had nephrotic-range proteinuria and in those with primary podocytopathy, with 62% of patients with nephrotic syndrome displaying a "positive" usCD163. In patients with AAV and significant proteinuria, usCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis. Conclusions usCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates usCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.

BACKGROUND AND OBJECTIVES: Membranoproliferative GN and C3 glomerulopathy are rare and overlapping disorders associated with dysregulation of the alternative complement pathway. Specific etiologic data for pediatric membranoproliferative GN/C3 glomerulopathy are lacking, and outcome data are based on retrospective studies without etiologic data. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 80 prevalent pediatric patients with membranoproliferative GN/C3 glomerulopathy underwent detailed phenotyping and long-term follow-up within the National Registry of Rare Kidney Diseases (RaDaR). Risk factors for kidney survival were determined using a Cox proportional hazards model. Kidney and transplant graft survival was determined using the Kaplan–Meier method. RESULTS: Central histology review determined 39 patients with C3 glomerulopathy, 31 with immune-complex membranoproliferative GN, and ten with immune-complex GN. Patients were aged 2–15 (median, 9; interquartile range, 7–11) years. Median complement C3 and C4 levels were 0.31 g/L and 0.14 g/L, respectively; acquired (anticomplement autoantibodies) or genetic alternative pathway abnormalities were detected in 46% and 9% of patients, respectively, across all groups, including those with immune-complex GN. Median follow-up was 5.18 (interquartile range, 2.13–8.08) years. Eleven patients (14%) progressed to kidney failure, with nine transplants performed in eight patients, two of which failed due to recurrent disease. Presence of >50% crescents on the initial biopsy specimen was the sole variable associated with kidney failure in multivariable analysis (hazard ratio, 6.2; 95% confidence interval, 1.05 to 36.6; P50% crescents on the initial biopsy specimen. CONCLUSIONS: Crescentic disease was a key risk factor associated with kidney failure in a national cohort of pediatric patients with membranoproliferative GN/C3 glomerulopathy and immune-complex GN. Presenting eGFR and crescentic disease help define prognostic groups in pediatric C3 glomerulopathy. Acquired abnormalities of the alternative pathway were commonly identified but not a risk factor for kidney failure.

While research has examined bystander responses in a traditional sense, there is a dearth of research regarding responses of cyberbystanders in a real-time situation, such as observing a cyberbullying scenario. This article describes a novel protocol designed to develop a series of images to be used to undertake research that aims to examine cyberbystander responses. A total of 24 scenarios (12 negative (cyberbullying) and 12 neutral) were created by the researchers and designed to mimic the way such scenarios would appear on a social networking site. The negative (cyberbullying) stimuli were rated in terms of level of severity, and the scenarios were compared to a selection of images from the International Affective Picture System using the Self-Assessment Manikin. These stimuli were compiled to form the Cyberbullying Picture Series (CyPicS). Through the development of the CyPicS, this protocol will aid future researchers in examining responses to real-life scenarios, as it is the first of its kind to develop these scenarios and test and evaluate them. CyPicS will provide researchers with the means to systematically evaluate responses to validated, real-life cyberbullying scenarios. More specifically, future researchers can utilize CyPicS to investigate how cyberbystanders respond when observing cyberbullying stimuli compared to neutral stimuli, as well as to measure and understand reactions or perceptions of cyberbullying. CyPicS can be used in any form of cyberbullying research (including electroencephalography and eye-tracking studies, psychological research, and functional magnetic resonance imaging studies) that may utilize bystander reactions and behaviors. Findings from research that utilizes CyPicS will greatly increase our understanding of bystander responses, and with variations in study design, researchers can further examine past or future associations with cyber-victim/bully status and mental health outcomes. Refereed/Peer-reviewed

BACKGROUND: 2-Hydroxyethyl mercapturic acid (2HEMA, N-acetyl-S-(2-hydroxyethyl)-L-cysteine) is a urinary metabolite of several volatile organic compounds including acrylonitrile and ethylene oxide, which are found in cigarette smoke. METHODS: We measured 2HEMA concentrations in urine specimens collected during the National Health and Nutrition Examination Survey (2011–2016) from eligible participants aged >12 years (N = 7,416). We developed two multiple linear regression models to characterize the association between cigarette smoking and 2HEMA concentrations wherein the dependent variable was 2HEMA concentrations among participants who exclusively smoked cigarettes at the time of specimen collection and the independent variables included sex, age, race/ethnicity, creatinine, diet, and either cigarettes smoked per day (CPD) or serum cotinine. RESULTS: We detected 2HEMA in 85% of samples tested among exclusive cigarette smokers, and only 40% of specimens from non-smokers. When compared to exclusive cigarette smokers who smoked 1–9 CPD, smoking 10–19 CPD was associated with 36% higher 2HEMA (p < 0.0001) and smoking >19 CPD was associated with 61% higher 2HEMA (p < 0.0001). Additionally, 2HEMA was positively associated with serum cotinine. CONCLUSIONS: This study demonstrates that cigarette smoking intensity is associated with higher urinary 2HEMA concentrations and is likely a major source of acrylonitrile and/or ethylene oxide exposure.

A high fruit and vegetable (FV) diet reduces asthma exacerbations in adults; this has not been examined in children to date.To investigate the effect of a 6-month, high FV diet on the time to first asthma exacerbation in children with asthma, in a parallel-group, randomized, controlled trial.Children (aged 3-11 years) with asthma, history of exacerbations and usual low FV intake (≤3 serves/day) were randomized to the intervention (high FV diet) or control group (usual diet) for 6 months. The primary outcome was time to first exacerbation requiring medical intervention. Secondary outcomes included exacerbation rate, lung function, plasma TNF-α, CRP, and IL-6, faecal microbiota and peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity and G-protein coupled receptor (GPR) 41/43 and HDAC (1-11) expression.67 children were randomized between September 2015 and July 2018. FV intake (difference in change (∆): 3.5 serves/day, 95% CI: [2.6, 4.4] p 0.001) and plasma total carotenoids (∆: 0.44 µg/ml [0.19, 0.70] p = 0.001) increased after 6 months (intervention vs control). Time to first exacerbation (HR: 0.81, 95% CI: [0.38, 1.69], p = 0.569; control vs. intervention) and exacerbation rate (IRR: 0.84, [0.47, 1.49], p = 0.553; control vs. intervention) were similar between groups. In per-protocol analysis, airway reactance z-scores increased in the intervention versus control group (XA high FV diet did not affect asthma exacerbations over the 6-month intervention, though warrants further investigation as a strategy for improving lung function and protecting against systemic inflammation in children with asthma.

Objective To investigate the individual and cumulative impact of childhood and adulthood adversity on allostatic load (AL) burden. Method Retrospective cross-sectional study design involving 4,165 participants from the first wave of The Irish Longitudinal study on Ageing (TILDA). AL was operationalized using 12 biomarkers across four physiological systems (cardiovascular, metabolic, renal, and immune). Measures of psychosocial adversity included poverty, abuse, loss, and illness. Negative binomial regression models estimated the relationship of individual adversities and a cumulative count of adversities with AL burden, controlling for age and sex. Multivariable models adjusted additionally for a range of other sociodemographic and lifestyle factors. Results Childhood poverty, childhood physical abuse, and having a spouse/partner/child experience a life-threatening illness/accident were associated with 10% (95% CI [1.04, 1,16]), 10% (95% CI [1.01, 1.18]), and 6% (95% CI [1.01, 1.11]) greater AL burden, respectively. Cumulative adversity was associated with 3% (95% CI [1.01, 1.04]) higher AL burden. Adjusting for sociodemographic and lifestyle covariates rendered the association of childhood poverty (IRR= 1.04, 95% CI [.98, 1.09]; p = .190) and childhood physical abuse (IRR= 1.07, 95% CI [.99, 1.15]; p = .081) with AL burden nonsignificant, while the association of having an ill spouse/partner/child on AL persisted (IRR= 1.06, 95% CI [1.01, 1.11]; p = .021). Conclusions This study provided limited support for the idea that psychosocial stress leads to higher AL, with just three out of 11 adversities associated with AL. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Falls remain the leading cause of unintentional pediatric trauma in the United States. Identifying risk factors for pediatric building falls would influence public health policy. We hypothesized that building falls disproportionately affect low income communities.We performed a cross-sectional analysis of the Kids' Inpatient Database for years 2006, 2009, and 2012. We identified cases (age12 years) of falls from a building using external cause of injury codes. Patient characteristics and injuries were analyzed using ICD-9 codes. National estimates were obtained using case weighting. Multivariable logistic regression was performed to adjust for confounders.There were 2,294 hospitalizations nationally for pediatric falls from a building. The victims were predominately male, in early childhood, non-Hispanic White, in the lowest income quartile, resided in urban settings, and occurred during summer. The mean age was 3.76 years. Logistic regression revealed males were 33% more likely than females, and as compared to non-Hispanic White youth, Black (33%) and Asian or Pacific Islanders (65%) were more likely to experience a fall from a building. Toddlers and those in early childhood were at significantly increased odds than those younger than one year old. Children in the highest income quartile were 29% more likely to experience a building fall.Building falls are a common cause of injury in the U.S. for children under 12 years old. Injury prevention strategies focused on the parents of children aged 1-5 years has the potential to make a significant public health impact.

Infant gastroesophageal reflux disease (GERD) is a significant cause of concern to parents. This study seeks to describe GERD prevalence in infants, evaluate possible risk factors and assess common beliefs influencing management of GERD among Asian parents.Mother-infant dyads in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort were prospectively followed from preconception to 12 months post-delivery. GERD diagnosis was ascertained through the revised Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R) administered at 4 time points during infancy. Data on parental perceptions and lifestyle modifications were also collected.The prevalence of infant GERD peaked at 26.5% at age 6 weeks, decreasing to 1.1% by 12 months. Infants exclusively breastfed at 3 weeks of life had reduced odds of GERD by 1 year (adjusted odds ratio 0.43, 95% confidence interval 0.19-0.97,Prevalence of GERD in infants is highest in the first 3 months of life, and the majority outgrow it by 1 year of age. Infants exclusively breastfed at 3 weeks had reduced odds of GERD. Cultural-based changes such as elimination of "heaty or cold" food influence parental perceptions in GERD, which are unique to the Asian population. Understanding the cultural basis for parental perceptions and health-seeking behaviours is crucial in tailoring patient education appropriately for optimal management of infant GERD.

BACKGROUND Developmental studies have shown adolescence is a period of ongoing white matter (WM) development, reduced sleep quality and the onset of many mental disorders. Findings indicate the WM development of the uncinate fasciculus (UF), a WM tract suggested to play a key role in mental disorders, continues throughout adolescence. While these studies provide valuable information, they are limited by long intervals between scans (1 to 4 years) leaving researchers and clinicians to infer what may be occurring between time-points. To allow inferences to be made regarding the impact that sleep quality may be having on WM development, longitudinal studies with much shorter between-scan intervals are required. METHODS The current study reports longitudinal data of self-reported sleep quality (PSQI), diffusion tensor imaging (DTI) measures of WM development and psychological distress (K10) for n = 64 early adolescents spanning the first twelve months (four time-points; Baseline, 4, 8, & 12 months) of the Longitudinal Adolescent Brain Study (LABS) study currently underway at the Thompson Institute. RESULTS Generalised Estimating Equation analysis showed a significant relationship between sleep quality and psychological distress over the four time-points. Reduced radial diffusivity and increased fractional anisotropy of the UF is also reported with increasing age suggesting that ongoing myelination is occurring. Adding sleep quality to the model, however, negatively impacted this myelination process. CONCLUSION These findings represent an important step towards elucidating how sleep, psychological distress and maturation of the UF may co-develop during early adolescence.

The current sports concussion assessment paradigm lacks reliability, has learning effects and is not sufficiently challenging for athletes. As a result, subtle deficits in sensorimotor function may be unidentified, increasing the risk of future injury. This study examined if the inertial-sensor instrumented Y Balance test could capture concussion induced alterations in dynamic movement control. A cohort of 226 elite Rugby Union, American Football and Ice Hockey athletes were evaluated using the inertial-sensor instrumented Y balance test. Dynamic balance performance was quantified using normalised reach distance, jerk magnitude root-Mean-Squared (Jerk Mag RMS) and gyroscope magnitude sample entropy (Gyro Mag SEn). Concussed athletes who consented to follow-up were evaluated 24 to 48-hours post-injury, and at the point of return to full contact training (RTP). Seventeen athletes sustained a concussion and consented to both the 24 to 48-hour and RTP follow-up testing. Twenty uninjured control athletes were re-tested 6-months following initial screening. Concussed athletes had reductions in normalised reach distance (Cohens D=0.66-1.16) and Jerk Mag (Cohens D=0.57-1.14) 24 to 48-hours post-injury, which returned to pre-injury levels by the point of RTP. There was no significant difference in performance between the baseline and 6-month follow-up in the 20 un-injured athletes (Cohens D=0.06-0.51). There was a statistically significant linear association between Jerk Mag RMS 24 to 48-hours post-injury and the natural log of RTP duration (R2= 0.27 to 0.33). These results indicate that concussed athletes possessed alterations in dynamic movement control 24 to 48-hours post-concussion, which typically returns to pre-injury levels by the point of RTP. Furthermore, evaluation of dynamic movement control 24 to 48 hours post injury may aid in the evaluation of recovery prognosis. Science Foundation Ireland Insight Research Centre

Background Prevention of violence due to severe mental disorders in psychiatric hospitals may require intrusive, restrictive and coercive therapeutic practices. Research concerning appropriate use of such interventions is limited by lack of a system for description and measurement. We set out to devise and validate a tool for clinicians and secure hospitals to assess necessity and proportionality between imminent violence and restrictive practices including de-escalation, seclusion, restraint, forced medication and others. Methods In this retrospective observational cohort study, 28 patients on a 12 bed male admissions unit in a secure psychiatric hospital were assessed daily for six months. Data on adverse incidents were collected from case notes, incident registers and legal registers. Using the functional assessment sequence of antecedents, behaviours and consequences (A, B, C) we devised and applied a multivariate framework of structured professional assessment tools, common adverse incidents and preventive clinical interventions to develop a tool to analyse clinical practice. We validated by testing assumptions regarding the use of restrictive and intrusive practices in the prevention of violence in hospital. We aimed to provide a system for measuring contextual and individual factors contributing to adverse events and to assess whether the measured seriousness of threating and violent behaviours is proportionate to the degree of restrictive interventions used. General Estimating Equations tested preliminary models of contexts, decisions and pathways to interventions. Results A system for measuring adverse behaviours and restrictive, intrusive interventions for prevention had good internal consistency. Interventions were proportionate to seriousness of harmful behaviours. A ‘Pareto’ group of patients (5/28) were responsible for the majority (80%) of adverse events, outcomes and interventions. The seriousness of the precipitating events correlated with the degree of restrictions utilised to safely manage or treat such behaviours. Conclusion Observational scales can be used for restrictive, intrusive or coercive practices in psychiatry even though these involve interrelated complex sequences of interactions. The DRILL tool has been validated to assess the necessity and demonstrate proportionality of restrictive practices. This tool will be of benefit to services when reviewing practices internally, for mandatory external reviewing bodies and for future clinical research paradigms.

Reduced access to school meals during public health emergencies can accelerate food insecurity and nutritional status, particularly for low-income children in urban areas. To prevent the exacerbation of health disparities, there is a need to understand the implementation of meal distribution among large urban school districts during emergencies and to what degree these strategies provide equitable meal access. Our case study of four large urban school districts during the COVID-19 pandemic aims to address these knowledge gaps. Guided by the Getting to Equity (GTE) framework, we conducted a mixed-methods study evaluating emergency meal distribution and strategy implementation in four large urban school districts (Chicago Public Schools, Houston Independent School District, Los Angeles Unified School District, and New York City Department of Education). We gathered data from school district websites on (1) meal service and delivery sites and (2) district documents, policies, communication, and resources. Using qualitative coding approaches, we identified unique and shared district strategies to address meal distribution and communications during the pandemic according to the four components of the GTE framework: increase healthy options, reduce deterrents, build on community capacity, and increase social and economic resources. We matched district census tract boundaries to demographic data from the 2018 American Community Survey and United States Department of Agriculture food desert data, and used geographic information systems (GIS) software to identify meal site locations relative to student population, areas of high poverty and high minority populations, and food deserts. We found that all districts developed strategies to optimize meal provision, which varied across case site. Strategies to increase healthy options included serving adults and other members of the general public, providing timely information on meal site locations, and promoting consumption of a balanced diet. The quantity and frequency of meals served varied, and the degree to which districts promoted high-quality nutrition was limited. Reducing deterrents related to using inclusive language and images and providing safety information on social distancing practices in multiple languages. Districts built community capacity through partnering with first responder, relief, and other community organizations. Increased social and economic resources were illustrated by providing technology assistance to families, childcare referrals for essential workers, and other wellness resources. Geospatial analysis suggests that service locations across cities varied to some degree by demographics and food environment, with potential gaps in reach. This study identifies strategies that have the potential to increase equitable access to nutrition assistance programs. Our findings can support (1) ongoing efforts to address child food insecurity during the pandemic and (2) future meal provision through programs like the Summer Food Service Program and Seamless Summer Option. Future research should further examine the rationale behind meal site placement and how site availability changed over time.

ObjectiveTo determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers.DesignA cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020.SettingUniversity Hospitals Birmingham NHS Foundation Trust (UHBFT), UK.Participants545 asymptomatic healthcare workers were recruited while at work. Participants were invited to participate via the UHBFT social media. Exclusion criteria included current symptoms consistent with COVID-19. No potential participants were excluded.InterventionParticipants volunteered a nasopharyngeal swab and a venous blood sample that were tested for SARS-CoV-2 RNA and anti-SARS-CoV-2 spike glycoprotein antibodies, respectively. Results were interpreted in the context of prior illnesses and the hospital departments in which participants worked.Main outcome measureProportion of participants demonstrating infection and positive SARS-CoV-2 serology.ResultsThe point prevalence of SARS-CoV-2 viral carriage was 2.4% (n=13/545). The overall seroprevalence of SARS-CoV-2 antibodies was 24.4% (n=126/516). Participants who reported prior symptomatic illness had higher seroprevalence (37.5% vs 17.1%, χ2=21.1034, pConclusions and relevanceWe identify differences in the occupational risk of exposure to SARS-CoV-2 between hospital departments and confirm asymptomatic seroconversion occurs in healthcare workers. Further investigation of these observations is required to inform future infection control and occupational health practices.

Background Enhanced recovery after surgery (ERAS) protocols are widely utilized for elective colorectal surgery to improve outcomes and decrease costs, but few studies have evaluated the impact of ERAS protocols on cost with respect to anatomic site of resection. This study evaluated the impact of ERAS protocol on elective colon resections by site and longitudinal impact over time. Methods A single-center retrospective cohort study of 598 consecutive patients undergoing elective colorectal resection before and after implementation of ERAS protocol from 2013 to 2017 was performed. The primary outcomes were length of stay (LOS) and cost. Comparative and multivariate inferential statistics were used to assess additional outcomes. Results A total of 598 patients (100 pre-ERAS vs 498 post-ERAS) were evaluated with an overall median LOS of 4 days for right and left colectomies and 3 days for transverse colectomies. When comparing type of resection before and after ERAS protocol introduction, an increased LOS for left hemicolectomies from 3.09 to 4.03 days ( P = .047) was noted, with all other comparisons failing to reach statistical significance. Over time, an initial decrease in LOS for MIS approach after protocol introduction was observed; however, this effect diminished in the ensuing years and had no significant effect overall. Total cost of care was significantly increased post-ERAS for all cohorts except transverse colectomies. No further statistically significant differences were found. Conclusion After an initial improvement in outcomes, continued utilization of ERAS protocols demonstrated no improvement in LOS compared to pre-ERAS data and increased cost overall for patients regardless of site of resection.

Practice patterns for the management of patent ductus arteriosus (PDA) in premature infants are changing with advances in medical management. We sought to determine the increased mortality for premature infants who had a PDA ligation with a co-existing diagnosis of intraventricular hemorrhage (IVH).Premature neonates (1 y old with known gestational week ≤36 wk) with a diagnosis of IVH were identified within the Kids' Inpatient Database (KID) for the years 2006, 2009, and 2012. Diagnoses and procedures were analyzed by ICD-9 codes and stratified by a diagnosis of PDA and procedure of ligation. Case weighting was used to make national estimations. Multivariable logistic regression was performed to adjust for confounders.We identified 7567 hospitalizations for premature neonates undergoing PDA ligation. The population was predominately male (51.6%), non-Hispanic white (41.1%), were from the lowest income quartile (33.1%), had a gestational week of 25-26 wk (34.0%), and a birthweight between 500 and 749 g (37.3%). There was an increased mortality (10.7% versus 6.3%, P 0.01) and an increased length of stay (88.2 d versus 74.4 d, P 0.01) in those with any diagnosis of IVH compared with those without. Adjusted multivariable logistic regression demonstrated that high-grade IVH (III or IV) was associated with a significantly increased risk of mortality in those undergoing PDA ligation (aOR 2.59, P 0.01). Specifically, grade III and IV were associated with an increased odds of in-hospital mortality (aOR 1.99 and 3.16, respectively, P 0.01).Attitudes regarding the need for surgical intervention for PDA have shifted in recent years. This study highlights that premature neonates with grade III or IV IVH are at significantly increased risk of mortality if undergoing PDA ligation during the same hospitalization.III.

Context Biomechanical analyses of cutting tasks have demonstrated kinematic differences associated with the noncontact knee-injury risk when the movement direction is unanticipated. Motor-motor dual tasks occur within dynamic environments and change the demand for attentional resources needed to complete athletic maneuvers, which may contribute to injury risk. Objective To investigate the influence of anticipation and motor-motor task performance on cutting biomechanics. Design Cross-sectional study. Setting Laboratory. Patients or Other Participants A total of 32 healthy, recreationally active men (age = 23.1 ± 3.6 years, height = 180.0 ± 7.0 cm, mass = 81.3 ± 17.3 kg) who self-reported regular participation in cutting sports. Intervention(s) Participants performed a 45° side-step cut on the dominant limb in a random order of conditions: anticipation (anticipated, unanticipated) and task (no ball throw, ball fake, ball throw). Main Outcome Measure(s) Triplanar trunk, hip, and knee angles were assessed throughout the stance phase using 3-dimensional motion capture. Data were analyzed using a time series of means calculated from initial contact to toe-off (0%–100%) with 90% confidence intervals. Mean differences between conditions were identified as regions of nonoverlapping confidence intervals, and those that occurred during the region of peak vertical ground reaction force (0%–25%) are presented. Results Regardless of anticipation, attending to a ball (ball throw) resulted in more trunk extension (range = 2.9°–3.7°) and less lateral trunk flexion toward the cutting direction (range = 5.2°–5.9°). Planning to attend to a ball (ball fake) resulted in less lateral trunk flexion toward the cutting direction (4.7°). During unanticipated cutting, more trunk rotation away from the cutting direction was observed when attending to a ball (range = 5.3°–7.1°). The interaction of anticipation and task had a similar influence on sagittal- and frontal-plane trunk position. Conclusions Motor-motor task performance and its interaction with anticipation induced an upright, neutral trunk position during side-step cutting, which has been associated with the risk for noncontact knee injury. Promoting task complexity during rehabilitation and injury-prevention programs may better prepare individuals to succeed when performing high-risk athletic maneuvers.

Background Dog bites are a common cause of pediatric trauma requiring hospital admission. We aim to describe pediatric bite victims, associated injuries and interventions. Methods Children (≤ 18 years old) were identified with an ICD-9 diagnosis of dog bite in the Kids' Inpatient Database for the years 2006, 2009 and 2012. National estimates were obtained using case weighting. Multivariable logistic regression was performed. Results We identified 6323 admissions for a dog bite with mean age of 6.63 years. Patients were predominately male (56.9%), non-Hispanic white (61.9%), resided in the South (35.1%), and in an urban environment (59.9%). Almost one third underwent a surgical procedure. Open wounds of the head, neck and trunk were the most common injury and decreased in prevalence with increasing age. Open wounds of the extremities were the second most common and the prevalence increased with increasing age. Children aged 1–4 and 5–10 years were both more than three times more likely to be admitted than those more than age 11. Conclusions Dog bite injuries are common for pediatric patients. Children less than age 11 are at greatest risk, particularly in the summer. Dog safety training should be focused on elementary and middle school children close to the start of summer vacation. Level of evidence III.

Background Few studies have analyzed pediatric spontaneous pneumothorax (SPTX) nationally. We sought to better define this patient population and explore the evolution of surgical management. Methods Patients (10-20 y old) with an International Classification of Diseases, Ninth Revision diagnosis of SPTX were identified within the Kids' Inpatient Database for the years 2006, 2009, and 2012. Diagnoses and procedures were analyzed by International Classification of Diseases, Ninth Revision codes. National estimates were obtained using case weighting. Results There were 11,792 pediatric SPTX hospitalizations, and patients were predominantly male (84.0%), non-Hispanic white (69.0%), with a mean age of 17.2 y (95% confidence interval, 17.2-17.3). Overall, 52.5% underwent tube thoracostomy as the primary intervention, and more than one-third had a major surgical procedure (34.9%). From 2006 to 2012, there was an increase in bleb excisions from 81.1% to 86.9% and an increase in mechanical pleurodesis from 64.2% to 69.0%. There was a significant change from a predominantly open thoracotomy approach in 2006 (76.1%) to a video-assisted thoracoscopic approach in 2012 (89.3%). Conclusions Pediatric admission for SPTX results in tube thoracostomy in more than half of the cases and surgery in approximately one-third of the cases. Surgical intervention has changed to a more minimally invasive approach during the last decade, and counseling to patients and their families should reflect these updated management strategies. Level of Evidence III.

Hypothalamic-pituitary-adrenal axis dysregulation is frequently observed in patients with depression, with increased levels of the glucocorticoid (GC) cortisol commonly reported. Hypothalamic-pituitary-adrenal axis dysregulation may be a consequence of impaired feedback inhibition due to GC receptor (GR) impairments or dysfunction, termed "glucocorticoid resistance." Here, our objective was to assess mRNA levels of GC-related markers (GR, FKBP5, serum glucocorticoid kinase 1 [SGK1]) in patients with depression versus controls and in patient samples after electroconvulsive therapy (ECT). We also examined the relationship between these GC-related markers and 24-item Hamilton Depression Rating Scale (HAM-D24) scores to assess the utility of using them as biological markers for depression or the therapeutic response to ECT.GR, FKBP5, and SGK1 mRNA levels were examined in whole blood samples from 88 medicated patients with depression pre-/post-ECT and 63 controls using quantitative real-time polymerase chain reaction. Exploratory subgroup correlational analyses were performed to determine the relationship between GR, FKBP5, and SGK1 and 24-item Hamilton Depression Rating Scale scores.GR, FKBP5, and SGK1 mRNA levels were significantly lower in medicated patients with depression compared with controls (P0.001, P = 0.03, P0.001, respectively), but ECT did not alter their levels (all P0.05). There was no relationship between GR, FKBP5, or SGK1 and 24-item Hamilton Depression Rating Scale scores.GR, FKBP5, and SGK1 do not seem to be involved in the peripheral molecular response to ECT and do not represent useful biomarkers for predicting the therapeutic response to ECT in a real-world clinical setting.

Design changes of nonpowder guns, including BB and air guns, have significantly increased their potential to injure. We sought to characterize the demographics of children injured with nonpowder weapons and the specific injuries suffered.A cross-sectional analysis of the study years 2006, 2009, and 2012 was performed by combining the Kids' Inpatient Database into a single dataset. We identified cases (age 21 years) of air gun injuries using external cause of injury codes. Patient characteristics and injuries were analyzed using ICD-9 codes, and national estimates were obtained using case weighting.There were 1028 pediatric admissions for nonpowder weapon related injuries. The victims were predominately male (87.0%), non-Hispanic white (52.3%), resided in the South (47.3%), and in the lowest income quartile (39.2%). Half required a major surgical procedure. The predominant injuries were open wounds to the head, neck, or trunk (40.3%), and contusion (22.5%). Notable other injuries were intracranial injury (9.1%) and blindness or vision defects (3.3%).The nonpowder weapons available to this generation can paralyze, blind, and cause lasting injury to children. Injuries frequently require surgical intervention, and these weapons should no longer be considered toys. Further research and legislation should be aimed at limiting children's access to these weapons.III.

Tryptophan and kynurenine pathway (KP) metabolites are implicated in the pathophysiology of depression. We aimed to investigate their plasma concentrations in medicated patients with depression (n = 94) compared to age- and sex-matched healthy controls (n = 57), and in patients with depression after electroconvulsive therapy (ECT) in a real-world clinical setting, taking account of co-variables including ECT modality and heterogenous psychopathology. Depression severity was assessed using the Hamilton Depression Rating Scale (HAM-D24). Tryptophan (TRP) and kynurenine (KYN) metabolite concentrations [anthranilic acid (AA), 3-hydroxyanthranilic acid (3HAA), picolinic acid (PA), kynurenic acid (KYNA), and xanthurenic acid (XA)] and KYNA/KYN and KYNA/quinolinic acid (QUIN) ratios were lower in patients compared to controls. For the total group there was no significant change in KP metabolites post-ECT or correlations with mood ratings. However, improvements in mood score were correlated with increased KYN, 3-hydroxykynurenine (3HK), 3HAA, QUIN, and KYN/TRP in a subgroup of unipolar depressed patients. Additionally, in remitters baseline KYN, 3HK, and QUIN were associated with baseline HAM-D24 scores, and changes in 3HK and 3HAA concentrations post-ECT correlated with improvement in mood. KYN, KYNA, AA, 3HK, XA, PA, and QUIN were increased in a smaller 3-month follow-up group (n = 19) compared to pre-ECT concentrations. Overall, the results indicate that ECT mobilizes the KP, where a moderate association between selected metabolites and treatment response in unipolar depressed patients is evident.

Objectives Carer quality-of-life (QoL) effects are recommended for inclusion in economic evaluations, but little is known about the relative performance of different types of QoL measures with carers. This study evaluated the validity and responsiveness of 3 care-related QoL measures (the Carer Experience Scale [CES], CarerQoL-7D, and ASCOT-Carer), 1 health-related QoL measure (the EQ-5D-5L), and 1 generic QoL measure (the ICECAP-A). Methods Validity and responsiveness were assessed in a UK sample of informal carers of adults with dementia, stroke, mental illness, or rheumatoid arthritis. A questionnaire containing the 5 QoL measures was posted to carers identified through the Family Resources Survey (N = 1004). Hypotheses regarding the anticipated associations between constructs related to the QoL of carers were tested to investigate construct validity and responsiveness. Results Each measure exhibited some level of construct validity. In general, larger effect sizes and stronger associations were detected for the ASCOT-Carer and ICECAP-A measures in the pooled sample and across all conditions. The 5 measures did not exhibit clear responsiveness to changes over a 12-month period in care recipient health status or hours of care provided per week. Conclusion The results of this study provide initial evidence of the validity of care-related, health-related, and generic QoL (capability) measures in informal carers of adults with 4 highly prevalent conditions. Care-related measures were not always more sensitive to constructs associated with QoL of carers compared with generic measures. The performance of the ICECAP-A was comparable with that of the best-performing care-related measure, the ASCOT-Carer.

Background: There is no evidence that being a rural or regional organ transplant recipient has adverse physical health outcomes post‐surgery compared with those experienced by people living in cities, but the impact of living remotely from transplant centres on psychosocial outcomes has not been explored. Objective: To identify the social, emotional, psychological, spiritual, informational and practical issues associated with being a regionally based organ transplant recipient or carer and determine how support services could be improved for this group. Design/ Setting/ Participants: Twenty‐two purposively sampled adult Australians who lived outside metropolitan centres and had received an organ transplant (n = 15) or were the primary carer of someone who had received one (n = 7), participated in semi‐structured, telephone interviews. Qualitative data were collected until data saturation was reached and were analysed using thematic analysis. Results: Five key themes (plus subthemes) were identified: (a) travelling for specialist transplant care takes a toll, (b) unique transplant‐related psychological and emotional issues experienced before and after transplants, (c) caring for transplant recipients is a demanding role, (d) lay, peer and professional support, including rural general practitioners and accommodation facilities, help ease the burden, but (e) significant barriers to accessing transplant‐focused psychosocial support exist. Conclusion: Novel methods of delivering targeted, transplant‐specific information and psychosocial care to rural transplant recipients and their carers, employers and rural health professionals require development and evaluation. Strategies might be delivered by peers or professionals via telehealth, telephone, social media or websites for example, depending on preferences and level of need. Refereed/Peer-reviewed

Recent research has shown that the perception of biological motion may be influenced by aspects of the observer’s personality. In this study, we sought to determine how participant characteristics (including demographics, response inhibition, autism spectrum quotient, empathy, social anxiety, and motion imagery) might influence the use of form and motion to identify the actor’s sex in biological motion displays. We varied the degree of form and motion in biological motion displays and correlated 76 young adult participants’ performances for identifying the actor’s sex in these varied conditions with their individual differences on variables of interest. Differences in the separate use of form and motion cues were predictive of participant performance generally, with use of form most predictive of performance. Female participants relied primarily on form information, while male participants relied primarily on motion information. Participants less able to visualize movement tended to be better at using form information in the biological motion task. Overall, our findings suggest that similar group level performances across participants in identifying the sex of the actor in a biological motion task may result from quite different individual processing.

Refereed/Peer-reviewed It has been suggested that biological markers that define mental health are different to those that define mental illness. The basal ganglia changes dramatically over adolescence and has been linked to wellbeing and mental health disorders in young people. However, there remains a paucity of research on wellbeing and brain structure in early adolescence. This cross-sectional study examined relationships between grey matter volume (GMV) of basal ganglia regions (caudate, putamen, pallidum and nucleus accumbens) and self-reported wellbeing (COMPAS-W), in a sample of Australian adolescents aged 12 years (N = 49, M = 12.6, 46.9% female). Significant negative associations were found between left hemisphere caudate GMV and scores on 'total wellbeing', 'composure' and 'positivity'. The results of this study indicate that smaller caudate GMV at age 12 is linked to increased subjective wellbeing. While seemingly counter-intuitive, our finding is consistent with previous research of decreased GMV in the pons and increased COMPAS-W scores in adults. Our results suggest that protective neurobiological factors may be identifiable early in adolescence and be linked to specific types of wellbeing (such as positive affect and optimism). This has implications for interventions targeted at building resilience against mental health disorders in young people.

Research shows that adolescents with mental illnesses have a bias for processing negative facial emotions, and this may play a role in impaired social functioning that often co-exists with a mental health diagnosis. This study examined associations between psychological and somatic problems and facial emotion recognition in early adolescence, as any processing biases in this age-group may be an early indicator of later mental illnesses. A community sample of 40 12-year-olds self-rated their symptoms of anxiety, depression, and somatization via two mental health screeners. They also completed a computerized emotion recognition task in which they identified photographs of 40 faces showing expressions of anger, fear, sadness, happiness, or neutral expression. Results showed that increased symptoms of anxiety, depression, and somatization were significantly associated with fewer correct responses to angry expressions. These symptoms were also associated with faster and more accurate recognition of fearful expressions. However, there was no association between mental health and recognition of sad affect. Finally, increased psychological and/or somatic symptomology was also associated with better identification of neutral expressions. In conclusion, youth with increased psychological and/or somatic problems exhibited a processing bias for negative anger and fear expressions, but not sadness. They showed better processing of neutral faces than youth with fewer psychological and/or somatic problems. Findings are discussed in relation to indicators of mental illnesses in early adolescence and the potential underpinning neural mechanisms associated with mental health and emotional facial recognition.

IntroductionOsteopenia and osteoporosis have been reported in adults with Complete Androgen Insensitivity Syndrome (CAIS). Little is known about changes in bone mineral density (BMD) in adolescents with CAIS and whether it is affected by early gonadectomy. Body composition data have not been reported.MethodsSingle-center, retrospective study of CAIS adolescents who underwent dual-energy x-ray absorptiometry (DXA) (Hologic, Horizon A). Body composition is presented as lean and fat mass indices (LMI, FMI). Z-scores for lumbar spine areal BMD (LBMD), total body less head (TBLH), bone mineral content (BMC), LMI, and FMI were calculated using female normative data. Results are expressed as median and min, max.ResultsSix females with genetically confirmed CAIS were identified—one with intact gonads and five with history of gonadectomy at 2–11 months. In the subject with intact gonads, LBMD-Z and TBLH BMC-Z were −1.56 and −1.26, respectively, at age 16 years. Among those with gonadectomy, LBMD-Z was −1.8 (−3.59 to 0.49) at age 15.6 years (12–16.8) and decreased in all three subjects who had longitudinal follow-up despite hormone replacement therapy (HRT). Adherence to HRT was intermittent. LMI-Z and FMI-Z were 0.1 (−1.39 to 0.7) and 1.0 (0.22 to 1.49), respectively.ConclusionsThese limited data indicate that adolescents with CAIS have bone mass deficit. Further studies are needed to understand the extent of BMD abnormalities and the effect of gonadectomy, especially early in childhood, and to establish the optimal HRT regimen for bone accrual. Data on lean mass are reassuring.

Here we present a study of two new Assistive Technology (AT) accessible digital assessments which were developed to address the current paucity of (English) spoken language comprehension assessments accessible to individuals who are both non-verbal and have profound motor impairments. Such individuals may rely heavily upon AT for communication and control. However, many assessments require that responses are given either verbally, by physical pointing or manipulating physical objects. A further problem with many assessments is their reliance upon static images to represent language components involving temporal, spatial or movement concepts. These new assessments aim to address some of these issues.The assessments were used with 2 young people who are non-verbal and have profound motor impairments (GMFCS level IV/V) and who use eye gaze as their primary method of communication and access. One assessment uses static images and the other short video clips to represent concepts containing temporal, spatial or movement elements. The assessments were carried out with each participant, both before and after an intervention, as part of a larger study.The assessments were accessible using AT (eye gaze) for both participants, although assessment scores varied. The design of the assessments particularly suited one participant who scored near maximum, but they appeared less suitable for the other participant.Making assessments AT accessible removes a barrier to assessing aspects of the spoken language comprehension abilities of some. Video may be a better medium for representing certain concepts within assessments compared with static images.IMPLICATIONS FOR REHABILITATIONThe new assessments provided a deeper understanding of two members of a group who are traditionally difficult to assess, using two alternative physically accessible methods of assessing the spoken language comprehension of the target group;Accessible assessments are important for assessing complex individuals in order to identify knowledge limitations and set therapy (and education) goals;The alternative access features of communication software can provide a "wrapper" for providing accessibility features to assessments;Video clips may be a better means of representing certain concepts in assessments compared to their static equivalents;Ensuring that assessments are physically accessible is sufficient for the assessment of some individuals, but for some "cognitive" accessibility also needs to be considered.

TDP-43 is a DNA/RNA binding protein, but whether its interactions with RNA are relevant to inclusion formation in ALS is unclear. Chen et al. report that mutated forms of TDP-43 that are unable to bind RNA have an increased tendency to aggregate, and can mediate toxicity by sequestering wild-type TDP-43., Amyotrophic lateral sclerosis (ALS) presents with focal muscle weakness due to motor neuron degeneration that becomes generalized, leading to death from respiratory failure within 3–5 years from symptom onset. Despite the heterogeneity of aetiology, TDP-43 proteinopathy is a common pathological feature that is observed in >95% of ALS and tau-negative frontotemporal dementia (FTD) cases. TDP-43 is a DNA/RNA-binding protein that in ALS and FTD translocates from being predominantly nuclear to form detergent-resistant, hyperphosphorylated aggregates in the cytoplasm of affected neurons and glia. Mutations in TARDBP account for 1–4% of all ALS cases and almost all arise in the low complexity C-terminal domain that does not affect RNA binding and processing. Here we report an ALS/FTD kindred with a novel K181E TDP-43 mutation that is located in close proximity to the RRM1 domain. To offer predictive gene testing to at-risk family members, we undertook a series of functional studies to characterize the properties of the mutation. Spectroscopy studies of the K181E protein revealed no evidence of significant misfolding. Although it is unable to bind to or splice RNA, it forms abundant aggregates in transfected cells. We extended our study to include other ALS-linked mutations adjacent to the RRM domains that also disrupt RNA binding and greatly enhance TDP-43 aggregation, forming detergent-resistant and hyperphosphorylated inclusions. Lastly, we demonstrate that K181E binds to, and sequesters, wild-type TDP-43 within nuclear and cytoplasmic inclusions. Thus, we demonstrate that TDP-43 mutations that disrupt RNA binding greatly enhance aggregation and are likely to be pathogenic as they promote wild-type TDP-43 to mislocalize and aggregate acting in a dominant-negative manner. This study highlights the importance of RNA binding to maintain TDP-43 solubility and the role of TDP-43 aggregation in disease pathogenesis.

Introduction Data from clinical trials have justified the promotion of fitness as a means to enhance facets of cognitive control and academic achievement in youth. However, such associations, when tested under real-world conditions, are equivocal. The purpose of this study, therefore, was to evaluate longitudinal associations between aerobic capacity (AC), weight status, and academic achievement within a large urban county. Methods Longitudinal data were obtained from a sample of third, fifth, and seventh grade students in schools within an urban county in Georgia. Data on body mass index (BMI) were available from 11,639 students; AC data from 5735 students. Data on both indicators were obtained through the established FitnessGram assessment battery with 2-yr changes calculated using standardized Z scores. Academic achievement data were available from three subjects (math, science, and reading) for third, fifth, and seventh grade students, and 2-yr changes were computed using changes in Z scores for each test. Data were analyzed using generalized logistic models to test associations between change in BMI and AC in relation to changes in academic achievement. Results Positive associations were observed between improvements in weight status and academic achievement for the fifth grade boys and girls ([reading] odds ratio [OR], 1.47; 95% confidence interval [CI], 1.25-1.72; [science] OR, 1.22; 95% CI, 1.04-1.42). Maintaining weight status was associated with improved scores in the third grade ([math] OR, 1.16; 95% CI, 1.012-1.327; [reading] OR, 1.47; 95% CI, 1.25-1.72) and fifth grade cohorts (math OR, 1.20; 95% CI, 1.00.1.43). For AC, no significant associations were found for any age cohort. Conclusions Modest associations between improvements in weight status, AC, and academic achievement are noteworthy, despite the lack of statistical significance for AC. The results provide a robust evaluation of associations between fitness and academic achievement.

Background Acute myeloid leukemia patients receive anthracycline-containing induction chemotherapy. Anthracyclines cause cardiotoxicity; however, there is a paucity of data reflecting the risk of cardiotoxicity in the acute myeloid leukemia population, and risk factors for development of reduced left ventricular ejection fraction are not well established in this population. Methods A retrospective cohort study of adult acute myeloid leukemia patients receiving anthracycline-containing induction chemotherapy between March 2011 and August 2017 was performed. Baseline and all additional cardiac monitoring within one year of induction were collected. Home medications and new medication initiation were determined via the electronic health record and new outpatient prescriptions. Results Of 97 evaluable patients, 25 (25.8%) developed reduced left ventricular ejection fraction and 18 (18.6%) experienced clinical heart failure within one year of induction. The median difference from baseline to lowest left ventricular ejection fraction was −5.0 percentage points, with a range of +10.0 to −52.5. The median time to onset of reduced left ventricular ejection fraction was 27 days, at a median cumulative anthracycline dose of 270 mg/m2. No patient-specific or medication-specific factors were significantly associated with the risk of developing reduced left ventricular ejection fraction. Of 14 patients started on medical management for reduced left ventricular ejection fraction, 10 (71%) responded to therapy. Conclusions In this retrospective analysis, we observed that acute myeloid leukemia patients experienced reduced left ventricular ejection fraction more quickly and at lower doses than previously reported in the solid tumor population. Reduced left ventricular ejection fraction was at least partially reversible in most patients started on medical management. Although no factors were significantly associated with decreased cardiomyopathy risk, future assessment of cardioprotective medications may be warranted.

BackgroundElectroconvulsive therapy (ECT) is the most acutely effective treatment for severe treatment-resistant depression. However, there are concerns about its cognitive side-effects and we cannot yet confidently predict who will experience these. Telomeres are DNA-protein complexes that maintain genomic integrity. In somatic cells, telomeres shorten with each cell division. Telomere length (TL) can thus provide a measure of ‘biological’ aging. TL appears to be reduced in depression, though results are mixed. We sought to test the following hypotheses: (1) that TL would be shorter in patients with depression compared to controls; (2) that TL would be a predictor of response to ECT; and (3) that shorter TL would predict cognitive side-effects following ECT.MethodWe assessed TL in whole blood DNA collected from severely depressed patients (n = 100) recruited as part of the EFFECT-Dep Trial and healthy controls (n = 80) using quantitative real-time polymerase chain reaction. Mood and selected cognitive measures, including global cognition, re-orientation time, and autobiographical memory, were obtained pre-/post-ECT and from controls.ResultsOur results indicate that TL does not differ between patients with depression compared to controls. TL itself was not associated with mood ratings and did not predict the therapeutic response to ECT. Furthermore, shorter baseline TL is not a predictor of cognitive side-effects post-ECT.ConclusionsOverall, TL assessed by PCR does not represent a useful biomarker for predicting the therapeutic outcomes or risk for selected cognitive deficits following ECT.

Summary Background Soluble fibre modulates airway inflammation in animal models. The aim of this study was to investigate the effects of soluble fibre supplementation, with and without a probiotic, on plasma short chain fatty acids (SCFA), airway inflammation, asthma control and gut microbiome in adults with asthma. Methods A randomised, double-blinded, placebo controlled 3-way cross-over trial in 17 subjects with stable asthma at the Hunter Medical Research Institute, Newcastle, Australia. Subjects received 3 × 7 day oral interventions in random order; soluble fibre (inulin 12 g/day), soluble fibre + probiotic (inulin 12 g/day + multi-strain probiotic >25 billion CFU) and placebo. Plasma SCFA, sputum cell counts and inflammatory gene expression, asthma control gut microbiota, adverse events including gastrointestinal symptoms were measured. Findings There was no difference in change in total plasma SCFA levels (μmol/L) in the placebo versus soluble fibre (Δmedian [95% CI] 16·3 [−16·9, 49·5], p = 0·335) or soluble fibre+probiotic (18·7 [−14·5, 51·9], p = 0·325) group. Following the soluble fibre intervention there was an improvement in the asthma control questionnaire (ACQ6) (∆median (IQR) -0·35 (−0·5, −0·13), p = 0·006), sputum %eosinophils decreased (−1.0 (−2·5, 0), p = 0·006) and sputum histone deacetylase 9 (HDAC9) gene expression decreased (−0.49 (−0.83, −0.27) 2-ΔCt, p = .008). Individual bacterial operational taxonomic units changed following both inulin and inulin+probiotic arms. Interpretation Soluble fibre supplementation for 7 days in adults with asthma did not change SCFA levels. Within group analysis showed improvements in airway inflammation, asthma control and gut microbiome composition following inulin supplementation and these changes warrant further investigation, in order to evaluate the potential of soluble fibre as a non-pharmacological addition to asthma management. Fund John Hunter Hospital Charitable Trust.

We present a rare case of Acute Interstitial Nephritis (AIN) that occurred following a re-trial of clozapine in a 56-year-old lady with schizoaffective disorder. On initial trial of clozapine, this patient felt generally unwell with respiratory symptoms. Her inflammatory markers were raised and her renal function showed a mild, transient deterioration which normalised on the day of cessation of clozapine. Two years later, clozapine was re-trialled due the refractory nature of her psychiatric symptoms. She subsequently developed renal failure and AIN was confirmed by renal biopsy. Renal function improved after cessation of clozapine; however, she never fully regained normal renal function.

INTRODUCTION: An intra-neural ganglion cyst of the lateral dorsal cutaneous branch of the sural nerve is rare, with only a few cases reported in the literature. MATERIALS AND METHODS: We carried out a retrospective investigation of patients with an intraneural ganglion cyst of the lateral dorsal cutaneous nerve. RESULTS: We present a case series of four patients with intra-neural ganglion cysts of the lateral dorsal cutaneous nerve, the distal continuation of the sural nerve at the lateral aspect of the foot. CONCLUSION: Intra-neural ganglion cysts of the lateral dorsal cutaneous nerve are rare. They represent a relatively uncommon source of lateral ankle pain, which can easily be diagnosed with ultrasound (US) and magnetic resonance imaging and managed effectively with US-guided aspiration or surgical excision.

Thioredoxin reductase-1 (TrxR1)-, glutathione reductase (Gsr)-, and Nrf2 transcription factor-driven antioxidant systems form an integrated network that combats potentially carcinogenic oxidative damage yet also protects cancer cells from oxidative death. Here we show that although unchallenged wild-type (WT), TrxR1-null, or Gsr-null mouse livers exhibited similarly low DNA damage indices, these were 100-fold higher in unchallenged TrxR1/Gsr–double-null livers. Notwithstanding, spontaneous cancer rates remained surprisingly low in TrxR1/Gsr-null livers. All genotypes, including TrxR1/Gsr-null, were susceptible to N -diethylnitrosamine (DEN)-induced liver cancer, indicating that loss of these antioxidant systems did not prevent cancer cell survival. Interestingly, however, following DEN treatment, TrxR1-null livers developed threefold fewer tumors compared with WT livers. Disruption of TrxR1 in a marked subset of DEN-initiated cancer cells had no effect on their subsequent contributions to tumors, suggesting that TrxR1-disruption does not affect cancer progression under normal care, but does decrease the frequency of DEN-induced cancer initiation. Consistent with this idea, TrxR1-null livers showed altered basal and DEN-exposed metabolomic profiles compared with WT livers. To examine how oxidative stress influenced cancer progression, we compared DEN-induced cancer malignancy under chronically low oxidative stress (TrxR1-null, standard care) vs. elevated oxidative stress (TrxR1/Gsr-null livers, standard care or phenobarbital-exposed TrxR1-null livers). In both cases, elevated oxidative stress was correlated with significantly increased malignancy. Finally, although TrxR1-null and TrxR1/Gsr-null livers showed strong Nrf2 activity in noncancerous hepatocytes, there was no correlation between malignancy and Nrf2 expression within tumors across genotypes. We conclude that TrxR1, Gsr, Nrf2, and oxidative stress are major determinants of liver cancer but in a complex, context-dependent manner.

Objective To examine the relationship between school lunch timing (before vs after recess) on physical activity (PA) during recess and energy balance and food intake at lunch. Methods A cross-sectional study design was used to examine lunch intake and PA during recess among fourth- and fifth-graders (n = 103) over 5 school days. Lunch and PA were measured using a weighted plate waste technique and accelerometry, respectively. Results Children who received lunch before recess accumulated lower residual energy (ie, energy intake at lunch minus energy expenditure during recess) and consumed a greater proportion of milk servings. No timing effects were observed for other lunch and PA variables. Conclusions and Implications Lunch intake and activity during recess are related to lunch timing policy. Findings warrant further examination using experimental and quasi-experimental studies to better understand the impact of timing on health behaviors.

In June 1962 at the age of 87 years, Sir Winston Churchill (1874–1965) fell over in his hotel room at the Hotel de Paris in Monte Carlo and sustained a fracture to the neck of his left femur. He was flown back to London and the fracture operated on at The Middlesex Hospital by two eminent orthopaedic surgeons, Mr Phillip Newman (1911–1994), Consultant to the The Middlesex Hospital and The Royal National Orthopaedic Hospital, Stanmore, and The Institute of Orthopaedics, London, and Professor Herbert Seddon (1903–1977), Consultant to the The Royal National Orthopaedic Hospital, Stanmore, and Director of The Institute of Orthopaedics under whom Churchill was admitted as a private patient. Churchill’s recovery was complicated by the development of deep vein thrombosis. During his convalescence, Churchill befriended Seddon who recorded his time with him in his private papers. On 21 August, Churchill was discharged to his home at 28 Hyde Park Gate which had been modified during his admission and made a return to public life in November 1962 at a dinner at the dining club he had originally founded, The Other Club.

Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA)-axis is commonly observed in patients with depression. The delayed feedback system that mediates inhibition of HPA-axis activation is regulated by glucocorticoid receptors (GRs) found in stress-responsive areas of the brain. Glucocorticoid-induced leucine zipper (GILZ) is a key molecule in glucocorticoid biology and is thought to mediate the downstream anti-inflammatory effects of GRs. Previous reports suggest that GILZ levels are altered in the blood and brains of patients with, and animal models of, depression. However, no study has yet investigated the effects of antidepressant treatment on GILZ. Therefore, our aim was to examine peripheral blood GILZ mRNA levels in patients with depression (n = 88) compared to age- and sex-matched healthy controls (n = 63), and in patients with depression following treatment with a course of electroconvulsive therapy (ECT). We also assessed the relationship between GILZ and mood and clinical outcomes following ECT. GILZ mRNA levels were assessed using qRT-PCR. GILZ levels were found to be significantly lower in patients with depression compared to controls (p 0.002), and ECT further decreased GILZ levels (p = 0.05). Both of these results survived adjustment for potential covariates. However, we found no association between GILZ and mood scores. Overall, these results suggest that GILZ is involved in the pathophysiology of depression and the peripheral molecular response to ECT.

The E2F transcription factors are a group of proteins that bind to the promotor region of the adenovirus E2 gene. E2F1, the first family member to be cloned, is linked to functions including cell proliferation and apoptosis, DNA repair, cell senescence and metabolism. We recently performed a deep sequencing study of micro-RNA changes in whole blood following ECT. Two micro-RNAs (miR-126-3p and miR-106a-5p) were identified and gene targeting analysis identified E2F1 as a shared target of these miRNAs. To our knowledge, no studies have examined E2F1 mRNA levels in patients with depression. Peripheral blood E2F1 mRNA levels were therefore examined in patients with depression, compared to healthy controls, and the effects of a course of ECT on peripheral blood E2F1 mRNA was investigated. Depressed patient and healthy control groups were balanced on the basis of age and sex. E2F1 mRNA levels were significantly lower in depressed patients in comparison to controls (p = .009) but did not change with ECT. There was no relationship between baseline E2F1 levels and depression severity, response to treatment, presence of psychosis or polarity of depression. There were no significant correlations between E2F1 levels and mood scores based on the HAM-D24. These results indicate that reduced peripheral blood E2F1 mRNA could be a trait feature of depression.

Introduction Transplant units are exploring strategies to increase the availability of donor kidneys. The use of en-bloc kidney transplantation (EBKT) from paediatric donors represents one potential solution. We present our long-term experience with paediatric EBKT among adult recipients. Methods Twenty-three paediatric to adult EBKTs were performed by the Irish National Kidney Transplant Service between 1990 and 2016. The primary outcome variable was long-term en-bloc allograft survival rate. Secondary outcome variables were incidence of allograft thrombosis, incidence of delayed graft function, overall patient survival and serum creatinine at most recent follow-up. Outcomes were compared to single kidney transplant recipients from the same time period. Results Mean donor age was 1.8 ± 0.97 years (range: 7 months to 3 years). Recipient age was 46 ± 12 years. Mean follow-up was 133 ± 64 months (range: 36–264). Overall graft survival was 100%, 91% and 80% after 1, 5 and 10 years respectively, compared to 92%, 79% and 61% in single kidney transplant recipients ( p = 0.04). There were 5 cases of allograft failure, 3 due to death from unrelated causes. Median time to graft failure was 108 months (range: 36–172). Mean serum creatinine was 72.6 ± 21.6 μmol/l after the follow-up period. There were no cases of graft thrombosis or delayed graft function. Overall survival was 96.4%, 88.0%, 76.23% and 50.5% at 1, 5, 10 and 20 years respectively. Conclusion En-bloc paediatric kidney transplantation is associated with excellent long-term allograft and patient survival and is a feasible strategy for increasing the transplant donor pool in carefully selected recipients.

BackgroundAsthma is the most frequent cause of hospitalisation among children; however, little is known regarding the effects of asthma on immune responses in children.ObjectiveThe present study aimed to evaluate cytokine responses of peripheral blood mononuclear cells (PBMCs), PBMC composition and lung function in children with and without asthma.MethodsUsing a case-control design, we compared 48 children with asthma aged 3-11 years with 14 age-matched healthy controls. PBMC composition and cytokine production including interferon (IFN)-γ, interleukin (IL)-1β, IL-5 and lL-6 following stimulation with rhinovirus-1B (RV1B), house dust mite (HDM) and lipopolysaccharide (LPS) were measured. Lung function was assessed using impulse oscillometry and nitrogen multiple breath washout.ResultsThe frequency of group 2 innate lymphoid cells were significantly higher in asthmatics and PBMCs from asthmatics had deficient IFN-γ production in response to both RV1B and LPS compared with controls (PConclusionOur study indicates that children with asthma have a reduced lung function in concert with impaired immune responses and altered immune cell subsets. Improving our understanding of immune responses to viral and bacterial infection in childhood asthma can help to tailor management of the disease.

Objectives We investigated the predictive value of subset scales and full versions of the Hamilton Rating Scale for Depression (HAMD) for therapeutic outcomes in ECT. Methods This secondary analysis of patients with major depression (N = 136; 63% female; age = 56.7 [SD = 14.8]) from the EFFECT-Dep trial (NCT01907217) examined the predictive value of Evans-6, Toronto-7, Gibbons-8 and Maier-Philip 6 HAMD subset scales and three ‘full’ versions (HAMD-17, HAMD-21 and HAMD-24) on therapeutic outcomes. We also examined early improvement on subset scales and full versions as predictors of response and remission and explored predictive abilities of individual HAMD-24 items. Results The subset scales and full scales lacked sufficient predictive ability for response and remission. Receiver operating characteristic curves identified a lack of discriminative capacity of HAMD subset scales and full versions at baseline to predict response and remission. Only the Maier-Philip-6 was significantly associated with percentage reduction in HAMD-24 scores from baseline to end of ECT course. Early improvement on most of the subset scales and full versions was a sensitive and specific predictor of response and remission. Four of the HAMD-24 items were significantly associated with response and one with remission. Conclusions Limited utility of the HAMD subset scales and full versions in this context highlight a need for more tailored depression rating scales for ECT.

Adolescence is a period of significant anatomical and functional brain changes, and complex interactions occur between mental health risk factors. The Longitudinal Adolescent Brain Study commenced in 2018, to monitor environmental and psychosocial factors influencing mental health in 500 adolescents, for 5 years. Participants are recruited at age 12 from the community in Australia’s Sunshine Coast region. In this baseline, cross-sectional study of N = 64 participants, we draw on the network perspective, conceptualising mental disorders as causal systems of interacting entities, to propose a Bayesian network (BN) model of lifestyle and psychosocial variables influencing chances of individuals being psychologically well or experiencing psychological distress. Sensitivity analysis of network priors revealed that psychological distress (Kessler-10) was most affected by eating behaviour. Unhealthy eating increased the chance of moderate psychological distress by 600%. Low social connectedness increased the chance of severe psychological disorder by 200%. Certainty for psychological wellness required 33% decrease in unhealthy eating behaviours, 11% decrease in low social connectedness, and 9% reduction in less physical activity. BN can augment clinician judgement in mental disorders as probabilistic decision support systems. The full potential of BN methodology in a complex systems approach to psychopathology has yet to be realised.

The school environment plays an important role in children’s diets and overall health, and policies for universal free school meals have the potential to contribute to positive child health outcomes. This systematic review evaluates studies examining the association between universal free school meals and students’ school meal participation rates, diets, attendance, academic performance, and Body Mass Index (BMI), as well as school finances. The search was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). A search for studies published in economically developed countries published through December 2020 was performed in PubMed, Education Resources Information Center (ERIC), Thomson Reuters’ Web of Science, and Academic Search Ultimate, followed by examining the references in the resultant literature. A total of 47 studies were identified and the Newcastle-Ottawa Scale (NOS) was applied to assess bias. Nearly all studies examining universal free school meals found positive associations with school meal participation. Most studies examining universal free school meals that included free lunch found positive associations with diet quality, food security, and academic performance, however, the findings of studies examining only universal free breakfast were mixed. Research findings were similarly mixed when examining attendance as an outcome. Concerns about adverse outcomes on student BMI were not supported by the literature, in fact, several studies detected a potentially protective effect of universal free school meals on BMI. Research examining the impact of universal free meals on school finances was limited, but suggest that lower-income school districts in the U.S. may have positive financial outcomes from participation in universal free school meal provisions. Additionally, providing free meals to students may be associated with improved household incomes, particularly among lower-income families with children. Further research is needed to examine the financial implications of universal free meals for both school districts and families. Overall, universal free school meals may have multiple benefits for students and countries should consider universal free school meal provisions with strong nutrition guidelines. (PROSPERO registration: CRD42020221782).

Telomerase, the DNA polymerase responsible for maintaining telomere length, has previously been implicated in depression and the response to antidepressant drugs. In this study, we aimed to compare telomerase activity in peripheral blood mononuclear cells between patients with severe depression recruited as part of the KEEP-WELL Trial (Ketamine for Depression Relapse Prevention Following ECT; NCT02414932) and age- and sex-matched healthy volunteers both at baseline/pre-ECT and at follow-up 1 month later for controls or in patients after a course of ECT. We found no differences in telomerase activity between patients with depression (n = 20) compared to healthy controls (n = 33) at baseline/pre-ECT, or between patients treated with ECT compared to controls at follow-up. In patients, telomerase activity was not associated with mood, as assessed by the 24-item Hamilton Rating Scale for Depression, or the duration of the current depressive episode. Additionally, we found no significant relationship between telomerase activity and exposure to recent or childhood adversity in either the patient or control groups. Overall, our results suggest that telomerase activity is not associated with depression, the therapeutic response to ECT, or exposure to adversity.