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Operating room (OR) fires are rare but devastating events requiring immediate and effective response. Virtual Reality (VR) simulation training can provide a safe environment for practice of skills in such highly stressful situation. This study assessed interprofessional participants’ ability to respond to VR-simulated OR fire scenarios, attitudes, numbers of attempt of the VR simulation do participants need to successfully respond to OR fires and does prior experience, confidence level, or professional role predict the number of attempts needed to demonstrate safety and pass the simulation. 180 surgical team members volunteered to participate in this study at Beth Israel Deaconess Medical Center, Boston, MA. Each participant completed five VR OR simulation trials; the final two trials incorporated AI assistance. Primary outcomes were performance scores, number of attempts needed to pass, and pre- and post-survey results describing participant confidence and experiences. Differences across professional or training role were assessed using chi-square tests and analyses of variance. Differences in pass rates over time were assessed using repeated measures logistic regression. One hundred eighty participants completed simulation testing; 170 (94.4%) completed surveys. Participants included surgeons (17.2%), anesthesiologists (10.0%), allied health professionals (41.7%), and medical trainees (31.1%). Prior to training, 45.4% of participants reported feeling moderately or very confident in their ability to respond to an OR fire. Eight participants (4.4%) responded safely on the first simulation attempt. Forty-three participants (23.9%) passed by the third attempt (VR only); an additional 97 participants (53.9%) passed within the 4–5th attempt (VR with AI assistance). Providers are unprepared to respond to OR fires. VR-based simulation training provides a practical platform for individuals to improve their knowledge and performance in the management of OR fires with a 79% pass rate in our study. A VR AI approach to teaching this essential skill is innovative, feasible, and effective.

Background Traumatic brain injury (TBI) can precipitate new-onset psychiatric symptoms or worsen existing psychiatric conditions. To elucidate specific mechanisms for this interaction, neuroimaging is often used to study both psychiatric conditions and TBI. This systematic review aims to synthesize the existing literature of neuroimaging findings among patients with anxiety after TBI. Methods We conducted a Preferred Reporting Items for Systematic Review and Meta-Analyses–compliant literature search via PubMed (MEDLINE), PsychINFO, EMBASE, and Scopus databases before May, 2019. We included studies that clearly defined TBI, measured syndromic anxiety as a primary outcome, and statistically analyzed the relationship between neuroimaging findings and anxiety symptoms. Results A total of 5982 articles were retrieved from the systematic search, of which 65 studied anxiety and 13 met eligibility criteria. These studies were published between 2004 and 2017, collectively analyzing 764 participants comprised of 470 patients with TBI and 294 non-TBI controls. Imaging modalities used included magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, electroencephalogram, magnetic resonance spectrometry, and magnetoencephalography. Eight of 13 studies presented at least one significant finding and together reflect a complex set of changes that lead to anxiety in the setting of TBI. The left cingulate gyrus in particular was found to be significant in 2 studies using different imaging modalities. Two studies also revealed perturbances in functional connectivity within the default mode network. Conclusions This is the first systemic review of neuroimaging changes associated with anxiety after TBI, which implicated multiple brain structures and circuits, such as the default mode network. Future research with consistent, rigorous measurements of TBI and syndromic anxiety, as well as attention to control groups, previous TBIs, and time interval between TBI and neuroimaging, are warranted. By understanding neuroimaging correlates of psychiatric symptoms, this work could inform future post-TBI screening and surveillance, preventative efforts, and early interventions to improve neuropsychiatric outcomes.

Background Hospital readmissions and outpatient visits contribute to the significant burden on healthcare systems. Obstructive sleep apnea (OSA) is a chronic medical condition that is associated with cardiovascular comorbidities and other chronic conditions. Inpatient and outpatient healthcare utilization rates in patients with OSA following hospitalization are unclear. Methods This. retrospective case-control cohort study utilized a nationwide database to assess if OSA is associated with higher healthcare utilization post-hospitalization. We compared healthcare utilization among patients with OSA versus without OSA between 2009-2014 after matching for demographic variables, geographic location, hospital environment, reason for admission, and severity of illness during hospitalization. We measured future healthcare utilization by the number of ICU admissions, hospital admissions, emergency room visits, and outpatient visits after being discharged from the index hospitalization. Results Two equal-sized cohorts comprised of 85,912 matched pairs were obtained. The OSA cohort demonstrated significantly higher rates of future ICU admissions, hospital admissions, emergency room visits, and outpatient visits. Matching for comorbid cardiovascular conditions continued to demonstrate higher healthcare utilization in the OSA group. Short-term outcomes during the index hospitalization were relatively similar between groups. Conclusions This retrospective database study demonstrated that OSA may be an independent marker of higher future healthcare utilization. On the other hand, the length of stay during the index hospitalization was not elevated. Prospective studies are needed to confirm these findings and investigate the impact of directing additional resources to inpatients with OSA.

BACKGROUND International Statistical Classification of Disease and Related Health Problems, 10th Revision codes (ICD-10) are used to characterize cohort comorbidities. Recent literature does not demonstrate standardized extraction methods. OBJECTIVE Compare COVID-19 cohort manual-chart-review and ICD-10-based comorbidity data; characterize the accuracy of different methods of extracting ICD-10-code-based comorbidity, including the temporal accuracy with respect to critical time points such as day of admission. METHODS Design: Retrospective cross-sectional study. MEASUREMENTS ICD-10-based-data performance characteristics relative to manual-chart-review. RESULTS Discharge billing diagnoses had a sensitivity of 0.82 (95% Confidence Interval [CI]: 0.79-0.85; comorbidity range 0.35-0.96). The past medical history table had a sensitivity of 0.72 (95% CI: 0.69-0.76; range 0.44-0.87). The active problem list had a sensitivity of 0.67 (95% CI: 0.63-0.71; range 0.47-0.71). On day of admission, the active problem list had a sensitivity of 0.58 (95% CI: 0.54-0.63; range 0.30-0.68) and past medical history table had a sensitivity of 0.48 (95% CI: 0.43-0.53; range 0.30-0.56). CONCLUSIONS AND RELEVANCE ICD-10-based comorbidity data performance varies depending on comorbidity, data source, and time of retrieval; there are notable opportunities for improvement. Future researchers should clearly outline comorbidity data source and validate against manual-chart-review. This article is protected by copyright. All rights reserved.

Background Escherichia coli is a major neonatal pathogen and the leading cause of early-onset sepsis in preterm newborns. Maternal E. coli strains are transmitted to the newborn causing invasive neonatal disease. However, there is a lack of data regarding the phenotypic and genotypic characterization of E. coli strains colonizing pregnant women during labor. Methods This prospective study performed at the University of Oklahoma Medical Center (OUHSC) from March 2014 to December 2015, aimed to investigate the colonization rate, and the phylogeny, antibiotic resistance traits, and invasive properties of E. coli strains colonizing the cervix of fifty pregnant women diagnosed with preterm labor (PTL). Molecular analyses including bacterial whole-genome sequencing (WGS), were performed to examine phylogenetic relationships among the colonizing strains and compare them with WGS data of representative invasive neonatal E. coli isolates. Phenotypic and genotypic antibiotic resistance traits were investigated. The bacteria’s ability to invade epithelial cells in vitro was determined. Results We recruited fifty women in PTL. Cervical samples yielded E. coli in 12 % (n=6). The mean gestational age was 32.5 (SD±3.19) weeks. None delivered an infant with E. coli disease. Phenotypic and genotypic antibiotic resistance testing did not overall demonstrate extensive drug resistance traits among the cervical E. coli isolates, however, one isolate was multi-drug resistant. The isolates belonged to five different phylogroups, and WGS analyses assigned each to individual multi-locus sequence types. Single nucleotide polymorphism-based comparisons of cervical E. coli strains with six representative neonatal E. coli bacteremia isolates demonstrated that only half of the cervical E. coli isolates were phylogenetically related to these neonatal invasive strains. Moreover, WGS comparisons showed that each cervical E. coli isolate had distinct genomic regions that were not shared with neonatal E. coli isolates. Cervical and neonatal E. coli isolates that were most closely related at the phylogenetic level had similar invasion capacity into intestinal epithelial cells. In contrast, phylogenetically dissimilar cervical E. coli strains were the least invasive among all isolates. Conclusions This pilot study showed that a minority of women in PTL were colonized in the cervix with E. coli, and colonizing strains were not phylogenetically uniformly representative of E. coli strains that commonly cause invasive disease in newborns. Larger studies are needed to determine the molecular characteristics of E. coli strains colonizing pregnant women associated with an increased risk of neonatal septicemia.

Parkinson's disease (PD) is a neurodegenerative disease that includes motor impairments, such as tremor, bradykinesia, and postural instability. Although eye movement deficits are commonly found in saccade and pursuit tasks, preservation of oculomotor function has also been reported. Here we investigate specific task and stimulus conditions under which oculomotor function in PD is preserved. Sixteen PD patients and 18 healthy, age-matched controls completed a battery of movement tasks that included stationary or moving targets eliciting reactive or deliberate eye movements: pro-saccades, anti-saccades, visually guided pursuit, and rapid go/no-go manual interception. Compared with controls, patients demonstrated systematic impairments in tasks with stationary targets: pro-saccades were hypometric and anti-saccades were incorrectly initiated toward the cued target in ∼35% of trials compared with 14% errors in controls. In patients, task errors were linked to short latency saccades, indicating abnormalities in inhibitory control. However, patients' eye movements in response to dynamic targets were relatively preserved. PD patients were able to track and predict a disappearing moving target and make quick go/no-go decisions as accurately as controls. Patients' interceptive hand movements were slower on average but initiated earlier, indicating adaptive processes to compensate for motor slowing. We conclude that PD patients demonstrate stimulus and task dependency of oculomotor impairments, and we propose that preservation of eye and hand movement function in PD is linked to a separate functional pathway through the superior colliculus-brainstem loop that bypasses the fronto-basal ganglia network. Our results demonstrate that studying oculomotor and hand movement function in PD can support disease diagnosis and further our understanding of disease progression and dynamics.SIGNIFICANCE STATEMENTEye movements are a promising clinical tool to aid in the diagnosis of movement disorders and to monitor disease progression. Although Parkinson's disease (PD) patients show some oculomotor abnormalities, it is not clear whether previously described eye movement impairments are task-specific. We assessed eye movements in PD under different visual (stationary vs moving targets) and movement (reactive vs deliberate) conditions. We demonstrate that PD patients are able to accurately track moving objects but make inaccurate eye movements toward stationary targets. The preservation of eye movements toward dynamic stimuli might enable patients to accurately act on the predicted motion path of the moving target. These results can inform the development of tools for the rehabilitation or maintenance of functional performance.

We report findings from two sensory preconditioning experiments in which rats consumed two flavoured solutions, each with two gustatory components (AX and BY), composed of sweet, bitter, salt, and acid elements. After this pre-exposure, rats were conditioned to X by pairing with lithium chloride. Standard sensory preconditioning was observed: Consumption of flavour A was less than that of B. We found that sensory preconditioning was maintained when X was added to A and B. Both experiments included one group of rats with lesions of the perirhinal cortex, which did not influence sensory preconditioning. We discuss our findings in the light of other sensory preconditioning procedures that involve the perirhinal cortex and conclude that differences in experimental variables invoke different mechanisms of sensory preconditioning, which vary in their requirement of the perirhinal cortex.

BST2/tetherin is a transmembrane protein with antiviral activity; it is synthesized following exposure to interferons, and restricts the release of budding virus particles by tethering them to the host cell membrane. We previously showed that BST2 is induced in primary neurons following measles virus (MV) infection or type I interferon; however, BST2 was dispensable for protection against challenge with neuron-restricted MV. Here, we define the contribution of BST-2 in neuronal MV infection. Surprisingly, and in contrast to its antiviral role in non-neuronal cells, murine BST2 promotes MV infection in brains of permissive mice and in primary neuron cultures. Moreover, BST2 expression was predominantly observed in the non-synaptic fraction of purified neurons. These studies highlight a cell-type dependent role of a well-characterized antiviral protein in enhancing neuronal infection.

Background Schizophrenia is associated with elevated levels of circulating C-reactive protein (CRP) and other inflammatory markers, but it is unclear whether these associations extend to psychotic symptoms occurring in adolescence in the general population. A symptom-based approach may provide important clues for apparent trans-diagnostic effect of inflammation, which is also associated with depression and other psychiatric disorders. Methods Based on data from 2421 participants from the Avon Longitudinal Study of Parents and Children birth cohort, we examined associations of serum CRP levels assessed around age 16 with ten positive and ten negative symptoms of psychosis assessed using questionnaires around age 17, using both individual symptoms and symptom dimension scores as outcomes. Regression models were adjusted for sex, body mass index, depressive symptoms, substance use, and other potential confounders. Results Most prevalent positive symptoms were paranoid ideation (4.8%), visual (4.3%) and auditory (3.5%) hallucinations. Negative symptoms were more strongly correlated with concurrent depressive symptoms (r=0.51; P, Highlights • We examined psychotic symptoms in adolescents from a population-based birth cohort. • Common positive symptoms were paranoid ideation, visual and auditory hallucinations. • Negative symptoms were correlated with depressive and positive symptoms. • CRP was similarly associated with positive and negative symptom dimension scores. • CRP was specifically associated with auditory hallucinations and anhedonia.

Funder: Department of Health (DH); doi: https://doi.org/10.13039/501100000276, Early psychosis is characterised by heterogeneity in illness trajectories, where outcomes remain poor for many. Understanding psychosis symptoms and their relation to illness outcomes, from a novel network perspective, may help to delineate psychopathology within early psychosis and identify pivotal targets for intervention. Using network modelling in first episode psychosis (FEP), this study aimed to identify: (a) key central and bridge symptoms most influential in symptom networks, and (b) examine the structure and stability of the networks at baseline and 12-month follow-up. Data on 1027 participants with FEP were taken from the National EDEN longitudinal study and used to create regularised partial correlation networks using the 'EBICglasso' algorithm for positive, negative, and depressive symptoms at baseline and at 12-months. Centrality and bridge estimations were computed using a permutation-based network comparison test. Depression featured as a central symptom in both the baseline and 12-month networks. Conceptual disorganisation, stereotyped thinking, along with hallucinations and suspiciousness featured as key bridge symptoms across the networks. The network comparison test revealed that the strength and bridge centralities did not differ significantly between the two networks (C = 0.096153; p = 0.22297). However, the network structure and connectedness differed significantly from baseline to follow-up (M = 0.16405, p =

Objective COVID-19 has disproportionately affected low-income communities and people of color. Previous studies demonstrated that race/ethnicity and socioeconomic status (SES) are not independently correlated with COVID-19 mortality. The purpose of our study is to determine the effect of race/ethnicity and SES on COVID-19 30-day mortality in a diverse, Philadelphian population. Methods This is a retrospective cohort study in a single center tertiary care hospital in Philadelphia, PA. The study includes adult patients hospitalized with polymerase-chain-reaction-confirmed COVID-19 between March 1st , 2020 and June 6th , 2020. The primary outcome was a composite of COVID-19 death or hospice discharge within 30 days of discharge. The secondary outcome was intensive care unit (ICU) admission. Results The study included 426 patients. 16.7% died, 3.3% were discharged to hospice, and 20.0% were admitted to the ICU. Using multivariable analysis, race/ethnicity was not associated with the primary nor secondary outcome. In Model 4, age greater than 75 (Odds Ratio [OR], 11.01; 95% confidence interval [CI], 1.96 to 61.97) and renal disease (OR 2.78; 95% CI, 1.31 to 5.90) were associated with higher odds of the composite primary outcome. "Very-low-income area" (OR 0.29; 95% CI, 0.12 to 0.71) and BMI 30-35 (OR 0.24; 95% CI, 0.08 to 0.69) were associated with lower odds of the primary outcome. Conclusions When controlling for demographics, SES, and comorbidities, race/ethnicity was not independently associated with the composite primary outcome. Very-low SES, as extrapolated from census-tract-level income data, were associated with lower odds of the composite primary outcome. This article is protected by copyright. All rights reserved.

Citrus canker (CC) is an economically important bacterial disease caused by Xanthomonas citri subsp. citri (Xcc). There is variability in resistance to CC among Citrus species. Previous transcriptomic studies have shown that Xcc downregulates biosynthesis of secondary metabolites at early stages of infection in susceptible citrus. However, in partially resistant calamondin (Citrus × microcarpa), increased secondary metabolite production has been reported post Xcc inoculation. We analyzed the calamondin transcriptome and discovered 3318 and 7740 differentially expressed (DE) genes between Xcc-inoculated and control samples at 2- and 5-days post inoculation (dpi), respectively. Among the DE genes, the phenylpropanoid biosynthesis (PPB) pathway, a major secondary metabolite synthesis pathway, was upregulated at early stages (2 dpi) of Xcc infection. Furthermore, in contrast to previous studies of susceptible Citrus species, pathways related to a resistance response (such as plant-pathogen interaction and MAPK signaling pathway) were upregulated whereas the pathways related to a susceptible response (such as auxin and gibberellin biosynthesis and cell wall degradation) were not significantly upregulated in calamondin. The transcriptomic regulation of plant hormone biosynthesis in calamondin was also different from the susceptible citrus. Thus, PPB may represent the principal biochemical pathway underlying CC resistance.

Introduction There exists substantial variability in the management of pelvic ring injuries among pelvic trauma surgeons. The objective of this study was to perform a comprehensive survey on the management of pelvic ring injuries among an international group of pelvic trauma surgeons to determine areas of agreement and disagreement. Methods A 45-item questionnaire was developed using an online survey platform and distributed to 30 international pelvic trauma surgeons. The survey consisted of general questions on the acute management of pelvic ring injuries and questions regarding 5 cases: Lateral compression (LC) type 1 injury, LC-3, Anterior-posterior compression (APC) type 3 injury, a combined vertical shear (VS) injury through the sacrum, and VS injury through sacroiliac joint. Respondents were shown blinded anteroposterior pelvis radiographs and axial computed tomography (CT) images for each case and asked if the injury needed fixation, the type of fixation, the order of fixation, and postoperative weight-bearing status. The Kappa statistic was calculated to assess agreement between respondents for each question. Results Nineteen out of 30 pelvic trauma surgeons completed the survey. Respondents practiced in Brazil (n = 1), Germany (n = 1), India (n = 1), Italy (n = 1) United Kingdom (n = 1), and the United States (n = 14). Of the 45 questions in this survey, 38 (84%) had minimal to no agreement among the respondents. There was moderate agreement, for performing lumbopelvic fixation when indicated, for anterior and posterior fixation of the LC-3 injury, and on forgoing EUA or stress X-rays for the APC-3 injury. There was strong agreement for open reduction and internal fixation of the anterior pelvic ring in the APC-3 injury and the VS injury through the SI joint. In contrast, LC-1 injury and combined VS pelvic ring injury through the sacrum had no areas of moderate to strong agreement. Discussion This study identified specific areas of pelvic ring injury management with minimal to no agreement among pelvic trauma surgeons. Future research should target these areas with a lack of agreement to decrease practice variability and improve patient outcomes.

OBJECTIVE To compare immediate quality of open reduction of femoral neck fractures by alternative surgical approaches. DESIGN Retrospective cohort study. SETTING Twelve Level 1 North American trauma centers. PATIENTS Eighty adults 18-65 years of age with isolated, displaced, OTA/AO type 31-B2 or -B3 femoral neck fractures treated with internal fixation. INTERVENTION Thirty-two modified Smith-Petersen anterior approaches versus 48 Watson-Jones anterolateral approaches for open reduction performed by fellowship-trained orthopaedic trauma surgeons. MAIN OUTCOME Reduction quality as assessed by 3 senior orthopaedic traumatologists as "acceptable" or "unacceptable" on AP and lateral postoperative radiographs. RESULTS No difference was observed in the rate of acceptable reduction by modified Smith-Petersen (81%) versus Watson-Jones (81%) approach (risk difference null, 95% confidence interval -17.4% to 17.4%, P = 1.00) with 90.4% panel agreement (Fleiss' weighted κ = 0.63, P < 0.01). Stratified analyses did not identify a significant difference in the rate of acceptable reduction between approaches when stratified by Pauwels angle, basicervical or transcervical fracture location, or posterior comminution. The Smith-Petersen approach afforded a better reduction when preoperative skeletal traction was not applied (RR = 1.67 [95% CI 1.10-2.52] vs. RR = 0.87 [95% CI 0.70-1.08], P = 0.006). CONCLUSIONS No difference was observed in the quality of open reduction of displaced femoral neck fractures in young adults when a Watson-Jones anterolateral approach versus a modified Smith-Petersen anterior approach was performed by orthopaedic trauma surgeons. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background Endoprosthetic reconstruction after oncologic resection of bone tumors requires stable fixation between the prosthesis and residual host bone. Compressive osseointegration has been developed as an alternative to traditional stemmed implants to address the challenges and complications of achieving this fixation. Sufficient time has now passed from the advent of compressive implants to allow for an assessment of the intermediate-term and long-term results of this form of fixation. Questions/purposes At a minimum follow-up of 10 years after implantation of a compressive osseointegration device for oncologic reconstruction: (1) What is the risk of periprosthetic fracture, aseptic loosening, or implant breakage resulting in revision surgery for endoprosthesis removal? (2) What is the long-term cortical response at the host-endoprosthesis interface as visualized on plain radiographs? Methods A single-center, retrospective study was performed between 2002 and 2010, in which 110 patients with primary bone sarcoma of the proximal or distal femur were considered for oncologic resection and reconstruction. Patients were considered for a compressive osseointegration endoprosthesis if they were 50 years of age or younger, had not previously received femoral radiation, had no metabolic disease impairing bone healing, were not diagnosed with metastatic disease, and had life expectancy greater than six months. Of the 110 patients, 25 were treated with a compressive osseointegration implant of the proximal or distal femur, and 85 patients were treated with conventional stemmed implants or amputation because of older age, advanced disease, metabolic comorbidities, inability to tolerate a nonweightbearing postoperative period, or in the case of rotationplasty, patient preference. All patients who received this device during the period of study were considered eligible for inclusion in this review. The median (range) age was 18 years (7 to 50), and 13 of 25 patients were men. Five patients died of disease before the minimum follow-up duration of 10 years; two underwent amputation due to local recurrence and three died with the implant in situ, leaving 20 patients for complete analysis. Median follow-up was 144 months, and all 20 surviving patients had a minimum follow-up of 10 years (121 to 230 months). The primary endpoint was reoperation and implant removal for periprosthetic fracture, aseptic loosening, or mechanical breakage of any component of the compressive device in the endoprosthesis. In final analysis, death was considered a competing event to revision surgery, and cumulative incidence was reported after competing-event analysis. A secondary aim was radiographic evaluation of the host-implant interface to assess the long-term cortical response to compressive osseointegration. Results Spindle fracture or loosening was noted in three patients, and the remaining 17 patients maintained the compression device until the final follow-up. The risk of reoperation for aseptic loosening, periprosthetic fracture, or mechanical breakage of the implant using a competing risks estimator was 12% at 10 years (95% CI 0% to 26%). These complications occurred within 29 months of the index surgery; no patients had implant loosening or mechanical breakdown after this initial period. On radiographic assessment, 14 patients demonstrated cortical hypertrophy of the bone-implant interface, six patients had maintenance of the native cortical contour, and no patients had cortical atrophy or narrowing at the implant interface.Conclusion Long-term follow-up in patients with compressive osseointegrative endoprosthetic devices demonstrated no late revisions because of periprosthetic fracture, aseptic loosening, or implant breakage in this cohort with a minimum 10-year follow-up. There was no evidence of late-onset cortical atrophy or stress shielding at the host-implant interface. This study supports the long-term stability of the interface between host bone and the endoprosthesis in compressive osseointegration devices. Level of evidence Level IV, therapeutic study.

Laparoscopic sleeve gastrectomy (LSG) may be complicated by postoperative pain, nausea, and vomiting, with consequent increases in length of stay (LOS), decreased patient satisfaction, and higher costs. While enhanced recovery after surgery (ERAS) protocols have been in circulation for many years, there is no standard ERAS protocol for bariatric surgery. Data were collected prospectively and compared to a historical control. All patients undergoing LSG, ages 18 to 75, were included in the pathway; those with preoperative chronic opioid use were excluded from our results. Statistical analysis was performed using t-statistics and chi-squared test. Ninety patients undergoing LSG, performed by a single surgeon, were included in our ERAS group from November 26, 2018, to April 30, 2019, and were compared to a historical control of 570 patients who underwent LSG over the previous 5 years (pre-ERAS). Measured outcomes included discharge opioid prescriptions issued, hospital length of stay, 30-day readmissions, reoperations, morbidity, and mortality. Ten (11%) ERAS patients vs 100% of pre-ERAS patients received opioid prescriptions upon, or after, discharge (p

Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer­tain. We conducted a “meta‐umbrella” systematic synthesis of umbrella reviews, which are systematic reviews of meta‐analyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on non‐purely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of meta‐analyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 meta‐analyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social contacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For non‐organic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or four‐five (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention‐deficit/hyperactivity disorder (ADHD), they were maternal pre‐pregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer’s disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class I‐III risk/protective factors were mostly involved in the early neurodevelopmental period. The evidence‐based atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expanding early intervention and preventive strategies for mental disorders.

Bariatric surgery produces weight loss in part by impacting appetite and eating behavior. Research suggests physical activity (PA) assists with regulation of appetite and eating during non-surgical weight loss, although whether PA carries similar benefits in the context of bariatric surgery is unknown.Evaluate associations of moderate-to-vigorous intensity PA (MVPA) and sedentary time (ST) with appetite sensations (hunger [homeostatic/hedonic], satiety) and eating regulation behaviors (restraint, disinhibition) before and during the initial year following bariatric surgery.Adult bariatric patients received an accelerometer to measure MVPA/ST and a smartphone to complete appetite/eating ratings at four semi-random times daily for 10 days at pre- and 3-, 6-, and 12-months post-surgery. Data were analyzed using generalized linear mixed models.Higher MVPA levels related to more satiety across time (This study is the first to show that MVPA and ST each associate with appetite and eating regulation in daily life before and during post-surgical weight loss. Results, while preliminary and requiring experimental confirmation, highlight potential for targeting bariatric patients' activity behaviors to enhance modulation of appetite, control of food intake, and resistance to overeating.

Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that reduces levels of low-density lipoprotein-cholesterol (LDL-C) in the plasma by inhibition of cholesterol synthesis in hepatic cells, which leads to up-regulation of hepatic LDL receptors. Bempedoic acid is approved as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. In this case study, we describe a patient with HeFH who had a prior excellent response to statin but unable to take the same, and a less than expected response to PCSK9i, in whom initiation of bempedoic acid led to a substantial reduction of LDL-C. Our findings suggest that patients who are quite responsive to statins may also be quite responsive to bempedoic acid, a medication that works in the same biochemical pathway as HMG-CoA reductase inhibitors. Additionally, this medication may be particularly effective at lowering LDL-C among individuals not on background statin therapy.

Background The purpose of the study was to identify genetic variants associated with rotator cuff disease by performing a genome-wide association study (GWAS) for shoulder impingement using the UK Biobank (UKB) cohort and then combining the GWAS data with a prior GWAS for rotator cuff tears. The loci identified by the GWAS and meta-analysis were examined for changes in expression following rotator cuff tearing using RNA sequencing. Methods A GWAS was performed using data from UKB with 3864 cases of shoulder impingement. The summary statistics from shoulder impingement and a prior study on rotator cuff tears were combined in a meta-analysis. Also, the previous association of 2 single-nucleotide polymorphisms (SNPs) with shoulder impingement from a published GWAS using the UKB was tested. Rotator cuff tendon biopsies were obtained from 24 patients with full-thickness rotator cuff tears who underwent arthroscopic rotator cuff repair (cases) and 9 patients who underwent open reduction internal fixation for a proximal humeral fracture (controls). Total RNA was extracted and differential gene expression was measured by RNA sequencing for genes with variants associated with rotator cuff tearing. Results The shoulder impingement GWAS identified 4 new loci: LOC100506457, LSP1P3, LOC100506207, and MIS18BP1/LINC00871. Combining data with a prior GWAS for rotator cuff tears in a meta-analysis resulted in the identification of an additional 7 loci: SLC39A8/UBE2D3, C5orf63, ASTN2, STK24, FRMPD4, ACOT9/SAT1, and LINC00890/ALG13. Many of the identified loci have known biologic functions or prior associations with diseases, suggesting possible biologic pathways leading to rotator cuff disease. RNA sequencing experiments show that expression of STK24 increases whereas expression of SAT1 and UBE2D3 decreases following rotator cuff tearing. Two SNPs previously reported to show an association with shoulder impingement from a prior UKB GWAS were not validated in our study. Conclusion This is the first GWAS for shoulder impingement in which new data from UKB enabled the identification of 4 loci showing a genetic association. A meta-analysis with a prior GWAS for rotator cuff tearing identified an additional 7 loci. The known biologic roles of many of the 11 loci suggest plausible biologic mechanisms underlying the etiology of rotator cuff disease. The risk alleles from each of the genetic loci can be used to assess the risk for rotator cuff disease in individual patients, enabling preventative or restorative actions via personalized medicine.

Older adults show both age-related decreases in resting state functional connectivity and diminished sensorimotor function. Exercise has emerged as an intervention that may mitigate or even reverse these age-related declines. Here we sought to understand whether exercise impacts resting state functional connectivity, and motor acquisition and learning in older adults. Forty-two healthy older adults rested or completed 3 sets of high-intensity interval exercise (3 minutes at 75% maximal power output and 3 minutes light intensity) for a total of 23 minutes, then immediately practiced a complex, implicit motor task with their non-dominant hand across five separate sessions. Participants completed resting stage functional MRI before the first and after the fifth day of practice; they also returned 24-hours and 35-days following their fifth day of practice to complete short- and long-term retention tests to assess motor learning. Independent component analysis of resting state functional MRI revealed increased connectivity in the frontoparietal, the dorsal attentional, and cerebellar networks in the exercise group relative to the rest group. Seed-based analysis showed strengthened connectivity between the limbic system and right cerebellum, and between the right cerebellum and bilateral middle temporal gyri. There was no motor learning advantage for the exercise group; both rest and exercise groups demonstrated motor learning as measured at the short- and long-term retention tests. Our data suggest that exercise paired with a challenging implicit motor learning task in older adults can augment resting state functional connectivity without enhancing behaviour beyond that stimulated by skilled motor practice.

International audience; ABSTRACT Background Blood lipid concentrations display high interindividual variability in response to dietary interventions, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explain a limited fraction of the variability of these complex phenotypes. Objective We aimed to identify combinations of SNPs associated with the variability in LDL cholesterol and triglyceride (TG) concentration changes following 5 dietary interventions. Design In a multicenter randomized crossover trial, 92 participants with elevated waist circumference and low HDL cholesterol concentrations consumed 5 isoenergetic diets for 4 wk: a diet rich in saturated fatty acids (SFAs) from cheese, SFA from butter, monounsaturated fatty acids (MUFAs), n–6 polyunsaturated fatty acids (PUFAs), and a diet higher in carbohydrates (CHO). The association between 22 candidate SNPs in genes involved in lipid and bile acid metabolism and transport and changes in LDL cholesterol and TG concentrations was assessed with univariate statistics followed by partial least squares regression. Results Endpoint LDL cholesterol concentrations were significantly different (cheese: 3.18 ± 0.04, butter: 3.31 ± 0.04, MUFA: 3.00 ± 0.04, PUFA: 2.81 ± 0.04, CHO: 3.11 ± 0.04 mmol/L; P

This study examined maternal characteristics that relate to child anxiety risk in a nonclinical sample. Parity and maternal respiratory sinus arrhythmia (RSA) were examined in relation to maternal overprotective parenting behavior, and then to child anxiety risk. Mothers (n = 151) and their 24-month-old children participated in a laboratory visit in which mothers completed questionnaires about their parenting demographics (i.e., parity), their overprotective parenting behavior, and child anxiety risk. Mothers’ RSA was measured during a 5-min. baseline period. Maternal overprotection was observed during a puppet show episode. Moderated mediation analyses revealed that first-time motherhood indirectly related to increased anxiety risk through greater overprotective parenting when mothers also had high RSA. Results suggest high baseline maternal psychophysiology indicative of regulation serves as a context by which parity relates to maternal overprotection. Engaging in overprotection may require higher, rather than lower, regulatory capabilities. First-time mothers may benefit from psychoeducation around the way in which their parasympathetic regulation relates to their parenting behaviors and contributes to increased child anxiety proneness.

Background Racial disparities among clinical trial participants present a challenge to assess whether trial results can be generalized into patients representing diverse races and ethnicities. The objective of this study was to evaluate the impact of race and ethnicity on treatment response in patients with advanced non‐small cell lung cancer (aNSCLC) treated with programmed cell death‐1 (PD‐1) or programmed cell death‐ligand 1 (PD‐L1) inhibitors through analysis of real‐world data (RWD). Materials and Methods A retrospective cohort study of 11,138 patients with lung cancer treated at hospitals within the Mount Sinai Health System was performed. Patients with confirmed aNSCLC who received anti‐PD‐1/PD‐L1 treatment were analyzed for clinical outcomes. Our cohort included 249 patients with aNSCLC who began nivolumab, pembrolizumab, or atezolizumab treatment between November 2014 and December 2018. Time‐to‐treatment discontinuation (TTD) and overall survival (OS) were the analyzed clinical endpoints. Results After a median follow‐up of 14.8 months, median TTD was 7.8 months (95% confidence interval, 5.4–not estimable [NE]) in 75 African American patients versus 4.6 (2.4–7.2) in 110 White patients (hazard ratio [HR], 0.63). Median OS was not reached (18.4–NE) in African American patients versus 11.6 months (9.7–NE) in White patients (HR, 0.58). Multivariable Cox regression conducted with potential confounders confirmed longer TTD (adjusted HR, 0.65) and OS (adjusted HR, 0.60) in African American versus White patients. Similar real‐world response rate (42.6% vs. 43.5%) and disease control rate (59.6% vs. 56.5%) were observed in the African American and White patient populations. Further investigation revealed the African American patient group had lower incidence (14.7%) of putative hyperprogressive diseases (HPD) upon anti‐PD‐1/PD‐L1 treatment than the White patient group (24.5%). Conclusion Analysis of RWD showed longer TTD and OS in African American patients with aNSCLC treated with anti‐PD‐1/PD‐L1 inhibitors. Lower incidence of putative HPD is a possible reason for the favorable outcomes in this patient population. Implications for Practice There is a significant underrepresentation of minority patients in randomized clinical trials, and this study demonstrates that real‐world data can be used to investigate the impact of race and ethnicity on treatment response. In retrospective analysis of patients with advanced non‐small cell lung cancer treated with programmed cell death‐1 or programmed cell death‐ligand 1 inhibitors, African American patients had significantly longer time‐to‐treatment discontinuation and longer overall survival. Analysis of real‐world data can yield clinical insights and establish a more complete picture of medical interventions in routine clinical practice., Racial disparities in clinical trials affect whether trial results can be generalized for diverse patient populations. This article evaluates real‐world data to assess the impact of race and ethnicity on treatment response in patients with advanced non‐small cell lung cancer treated with PD‐1 or PD‐L1 inhibitors.

High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment for chemosensitive relapsed classical Hodgkin lymphoma, although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR classical Hodgkin lymphoma patients treated with HDC/ASCT at our institution between 01/01/2005 and 12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring more than one salvage line, or positron emission tomography (PET)-positive disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (n=146), busulphan/melphalan (BuMel) (n=38), gemcitabine( Gem)/BuMel (n=189) and vorinostat/Gem/BuMel (n=128). The Gem/BuMel and vorinostat/Gem/BuMel cohorts had more HRR criteria and more patients with PET-positive disease at ASCT. Treatment with brentuximab vedotin (BV) or anti-PD1 prior to ASCT, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). The median follow-up is 50 months (range, 6-186). Outcomes improved over time, with 2-year progressionfree survival (PFS)/overall survival (OS) rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016- 2019) (P

Background Probiotics have been demonstrated to ameliorate clinical signs of gastrointestinal diseases in dogs in various studies. However, the effect of probiotics in a healthy population, as well as factors contributing individualized responses, remain largely unknown. This trial examined gut microbiota (GM) and health outcomes in household dogs after synbiotic (SN) supplementation containing probiotics and inulin (a prebiotic). Healthy dogs were randomized to receive SN (50 mg/d inulin and 20 billion total CFU/d of L. reuteri, P. acidilactici, E. faecium, L. acidophilus, B. animalis, L. fermentum, L. rhamnosus) or placebo (PL) for 4 weeks. Owners completed a health survey and collected stool samples for GM profiling (shotgun metagenomic sequencing) at baseline and week 4 in both groups, and at week 6 in the SN group. Results A significant shift (p n = 24), but not PL group (n = 19), at week 4 relative to baseline. Forty-five bacterial species, 43 (96%) of which were Lactobacillales, showed an increase in the relative abundances (≥2 fold change, adjusted p E. coli also decreased at week 4 in the SN group (2.8-fold, adjusted p Proteobacteria and lower Lactobacillales responded more robustly to supplementation in terms of the change in β-diversity. Dogs fed SN tended to have lower diarrhea incidence (0% vs 16%, p = 0.08). Conclusions SN supplement had a short-term impact on the gut microbiota in healthy household dogs as characterized by shotgun metagenomic sequencing. Findings warrant further investigation with longer duration and populations at risk of gastrointestinal diseases. The magnitude of response to the supplement was associated with microbial profile at baseline. To our knowledge, this is the first study documenting such association and may provide a basis for personalized nutrition in companion dogs.

Islet transplantation is an emerging treatment for type 1 diabetes which offers the prospect of physiological control of blood glucose and reductions in acute hypoglycaemic episodes. However, current protocols are limited by a rapid decline in islet functional viability during the isolation process, culture period, and post‐transplantation. Much of this can be attributed to the deleterious effects of hypoxic and cytokine stressors on β cells. One experimental strategy to improve the functional viability of islets is coculture or cotransplantation with mesenchymal stromal cells (MSCs). Numerous studies have shown that MSCs have the capacity to improve islet survival and insulin secretory function, and the mechanisms of these effects are becoming increasingly well understood. In this review, we will focus on recent studies demonstrating the capacity for MSCs to protect islets from hypoxia‐ and cytokine‐induced stress. Islets exposed to acute hypoxia (1%‐2% O2) or to inflammatory cytokines (including IFN‐γ, TNF‐α, and IL‐B) in vitro undergo apoptosis and a rapid decline in glucose‐stimulated insulin secretion. Coculture of islets with MSCs, or with MSC‐conditioned medium, protects from these deleterious effects, primarily with secreted factors. These protective effects are distinct from the immunomodulatory and structural support MSCs provide when cotransplanted with islets. Recent studies suggest that MSCs may support secretory function by the physical transfer of functional mitochondria, particularly to metabolically compromised β cells. Understanding how MSCs respond to stressed islets will facilitate the development of MSC secretome based, cell‐free approaches to supporting islet graft function during transplantation by protecting or repairing β cells., The functional viability of pancreatic islets rapidly declines during isolation, culture, and post‐transplantation. Transplantation stressors can be modeled in vitro by exposing islets to acute hypoxia or inflammatory cytokines. This review covers research demonstrating that coculture of islets with mesenchymal stromal cells (MSCs), or with MSC‐conditioned medium, protects from these deleterious effects, primarily by MSC‐secreted factors, and the clinical implications of this.

Background The association between sexual and physical abuse and subsequent depression is well-established, but the associations with specific depressive symptoms and sex differences remain relatively understudied. We investigated the associations of sexual and physical abuse with depressive symptoms in men and women in a large population cohort. Methods Observational study based on 151,396 UK Biobank participants. Exposures included self-reported experiences of childhood physical abuse and sexual abuse. Mid-life outcomes included current depressive symptoms score, individual depressive symptoms, and lifetime depression. We used logistic regression to test associations of childhood sexual/physical abuse with depressive outcomes. Results Recalled childhood sexual and physical abuse were both associated with current depressive symptoms score in adults. Results for individual symptoms-based analyses suggest that sexual and physical abuse are associated with all depressive symptoms, particularly suicidal behaviours. The associations between lifetime depression and sexual/physical abuse were not fully explained by current depressive symptoms score, indicating that these findings may not be fully attributable to recall bias. There was no indication of differential risk for specific depressive symptoms among men and women. Conclusions Sexual and physical abuse are robust risk factors for depression/depressive symptoms regardless of sex. Higher risk of suicidal behaviours associated with childhood sexual/physical abuse are of particular concern. Longitudinal research into sex-specific associations for individual depressive symptoms is required.

BackgroundNonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents.MethodsComputerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance. Participants were adolescents aged 15 to 17 with (n = 50) and without (n = 190) NSSI history, sampled from the ROOTS project which recruited adolescents from secondary schools in Cambridgeshire, UK. NSSI was categorized as sporadic (1-3 instances per year) or repetitive (4 or more instances per year). Analyses were carried out in a series of linear and negative binomial regressions, controlling for age, gender, intelligence, and recent depressive symptoms.ResultsAdolescents with lifetime NSSI, and repetitive NSSI specifically, made significantly more perseverative errors on the Probabilistic Reversal Task and exhibited significantly lower quality of decision making on the Cambridge Gambling Task compared to no-NSSI controls. Those with sporadic NSSI did not significantly differ from no-NSSI controls on task performance. NSSI was not associated with behavioral measures of impulsivity.ConclusionsRepetitive NSSI is associated with increased behavioral compulsivity and disadvantageous decision making, but not with behavioral impulsivity. Future research should continue to investigate how neurocognitive phenotypes contribute to the onset and maintenance of NSSI, and determine whether compulsivity and addictive features of NSSI are potential targets for treatment.

BACKGROUND Graduate medical education is being transformed from a time-based training model to a competency-based training model. While the application of ultrasound in the perioperative arena has become an expected skill set for anesthesiologists, clinical exposure during training is intermittent and nongraduated without a structured program. We developed a formal structured perioperative ultrasound program to efficiently train first-year clinical anesthesia (CA-1) residents and evaluated its effectiveness quantitatively in the form of a proficiency index. METHODS In this prospective study, a multimodal perioperative ultrasound training program spread over 3 months was designed by experts at an accredited anesthesiology residency program to train the CA-1 residents. The training model was based on self-learning through web-based modules and instructor-based learning by performing perioperative ultrasound techniques on simulators and live models. The effectiveness of the program was evaluated by comparing the CA-1 residents who completed the training to graduating third-year clinical anesthesia (CA-3) residents who underwent the traditional ultrasound training in the residency program using a designed index called a "proficiency index." The proficiency index was composed of scores on a cognitive knowledge test (20%) and scores on an objective structured clinical examination (OSCE) to evaluate the workflow understanding (40%) and psychomotor skills (40%). RESULTS Sixteen CA-1 residents successfully completed the perioperative ultrasound training program and the subsequent evaluation with the proficiency index. The total duration of training was 60 hours of self-based learning and instructor-based learning. There was a significant improvement observed in the cognitive knowledge test scores for the CA-1 residents after the training program (pretest: 71% [0.141 ± 0.019]; posttest: 83% [0.165 ± 0.041]; P < .001). At the end of the program, the CA-1 residents achieved an average proficiency index that was not significantly different from the average proficiency index of graduating CA-3 residents who underwent traditional ultrasound training (CA-1: 0.803 ± 0.049; CA-3: 0.823 ± 0.063, P = .307). CONCLUSIONS Our results suggest that the implementation of a formal, structured curriculum allows CA-1 residents to achieve a level of proficiency in perioperative ultrasound applications before clinical exposure.

Background Human milk oligosaccharides (HMOs) are complex glycans that are highly abundant in human milk. While over 150 HMOs have been identified, it is unknown how individual HMOs change in concentration over 24 months of lactation. Objectives To understand how HMO concentrations change over 24 months of lactation. Methods Breast milk samples were collected from participants in a longitudinal cohort study of Hispanic mother-infant pairs at 1, 6, 12, 18, and 24 months postpartum. Concentrations of 19 of the most abundant HMOs were measured using HPLC. Because the parent study is ongoing and not all participants have finished all time points yet, the sample sizes ranged per time point (n = 207 at 1 month; n = 109 at 6 months; n = 83 at 12 months; n = 59 at 18 months; and n = 28 at 24 months). Approximately 88% of participants were classified as HMO secretors-a genetic factor that affects concentrations of HMOs such as 2'fucosyllactose (2'FL) and lacto-N-fucopentaose I-while the remaining 12% were classified as nonsecretors. Mixed models were used to examine changes in HMO concentrations and relative abundances over the course of lactation. Results The majority of HMOs significantly decreased in concentration over the course of lactation. The exceptions were 2'FL, sialyl-lacto-N-tetraose b, and disialyl-lacto-N-tetraose, which did not change with time, and 3-fucosyllactose (3FL) and 3'-sialyllactose (3'SL), which significantly increased. The concentration of 3FL increased 10-fold, from 195 (IQR 138-415) μg/mL at 1 month to 1930 (1100-2630) μg/mL at 24 months, while 3'SL increased 2-fold, from 277 (198-377) μg/mL to 568 (448-708) μg/mL over the same time period. Conclusions These results indicate that HMOs do not decrease in concentration uniformly across lactation. In particular, 3FL and 3'SL increased over the course of lactation in this cohort. Future studies are required to fully understand the functions of these HMOs.

Objectives To determine the factors associated with successful union and eradication of infection in the setting of staged procedures to treat obviously infected nonunions of long bones. We hypothesize that patients with positive intraoperative cultures obtained at the time of definitive surgery for infected nonunions are more likely to have persistent nonunion than those with negative cultures. Design Multicenter retrospective review. Setting Eight academic Level 1 trauma centers. Patients/participants Patients who underwent staged management for obviously infected nonunion of a long bone. Main outcome measurements For each patient, initial fracture management, management of retained implants, number of debridements, grafting, bacteriology, antibiotic course, bone defect management, soft-tissue coverage, and definitive surgery performed were reviewed. Results A total of 134 patients were treated with staged procedures for obviously infected nonunion of a long bone (mean age 49 years, 60% open fractures, and mean follow-up 22 months). During definitive procedures, 120 patients had intraoperative cultures taken with 43% having positive cultures. For culture-positive patients, 41 patients achieved eventual union and 10 had persistent nonunion. Of 69 culture-negative patients, 66 achieved eventual union and 3 had persistent nonunion. The number of patients with union versus persistent nonunion was statistically significant between culture-positive and culture-negative groups (P = 0.015). Conclusions Management of infected nonunion in long bones with staged treatments before definitive fixation are beneficial but ultimately less effective when performed in the setting of positive bacterial cultures at the time of definitive management. Level of evidence Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

STUDY OBJECTIVE To compare the Fundamentals of Laparoscopic Surgery (FLS) exam scores between obstetrics and gynecology (OBGYN) and general surgery (GS) providers. DESIGN This is a retrospective cohort study at a single institution from July 2007 to May 2018. Categorical and continuous variables were analyzed with χ2 test, t test, and Wilcoxon rank sum test. SETTING Beth Israel Deaconess Medical Center (BIDMC), Boston, MA, a tertiary care academic medical center. PATIENTS All providers who took the FLS exam at the Carl J. Shapiro Simulation and Skills Center at BIDMC. INTERVENTIONS FLS certification. MEASUREMENTS AND MAIN RESULTS A total of 205 BIDMC trainees and faculty took the FLS exam between July 2007 and May 2018, of which 176 were identified to be OBGYN or GS providers. The FLS certification pass rate was high for both specialties (97.0% OBGYN vs 96.1% sGS, p = .76). When comparing all providers, no significant difference was found in the mean manual skill test scores between surgical specialties (594.9 OBGYN vs 601.0 GS, p = .59); whereas, a significant difference was noted in the mean cognitive scores, with GS providers scoring higher than OBGYN providers (533.8 OBGYN vs 583.4 GS, p

Two cases of primary distal femur osteosarcoma with subsequent metastasis to the abdomen are presented. In both cases, the development of abdominal metastasis was quickly followed by patient decline and death. A review of the literature was performed, assessing the presentation and survival of patients with osteosarcoma metastasized to the abdomen. As illustrated by the current cases and the literature review, abdominal metastasis in osteosarcoma is often a late manifestation and terminal prognostic indicator. Nonetheless, early detection and prompt intervention of this less common site of disease metastasis may improve patient care and palliative therapy.

Sarcoma comprises a group of malignancies that includes over 100 individual disease entities. Type-specific genetic events initiate each tumor, occurring within a specific cellular context or circumstance. All sarcomas share a relationship with mesenchymal tissues of origin. Conceptual models for each specific route towards sarcomagenesis have developed over the years as clinical, cellular, and increasingly molecular observations have advanced hypotheses to be tested in the forward or reverse direction in experimental systems, often genetically engineered model organisms. This review considers the history of these discoveries in the context of technologies available at the time each was made and provides a comprehensive summary of the current knowledge of sarcoma genetics, including characteristic translocations, oncogene activation and loss of tumor suppressor gene events, and their putative cells of origin. Also considered are the interrelatedness of molecular clinical observations and genetic experiments in model systems to move this field of knowledge forward, as well as their implications for diagnostic and therapeutic paradigms for sarcoma. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Excessive consumption of sugar and other unhealthy dietary factors during early life developmental periods yields changes in the gut microbiome as well as neurocognitive impairments. However, it is unclear whether these two outcomes are functionally connected. Here we explore whether excessive early life consumption of added sugars negatively impacts memory function via the gut microbiome. Rats were given free access to a sugar-sweetened beverage (SSB) during the adolescent stage of development. Memory function and anxiety-like behavior were assessed during adulthood and gut bacterial and brain transcriptome analyses were conducted. Taxa-specific microbial enrichment experiments examined the functional relationship between sugar-induced microbiome changes and neurocognitive and brain transcriptome outcomes. Chronic early life sugar consumption impaired adult hippocampal-dependent memory function without affecting body weight or anxiety-like behavior. Adolescent SSB consumption during adolescence also altered the gut microbiome, including elevated abundance of two species in the genus Parabacteroides (P. distasonis and P. johnsonii) that were negatively correlated with hippocampal function. Transferred enrichment of these specific bacterial taxa in adolescent rats impaired hippocampal-dependent memory during adulthood. Hippocampus transcriptome analyses revealed that early life sugar consumption altered gene expression in intracellular kinase and synaptic neurotransmitter signaling pathways, whereas Parabacteroides microbial enrichment altered gene expression in pathways associated with metabolic function, neurodegenerative disease, and dopaminergic signaling. Collectively these results identify a role for microbiota “dysbiosis” in mediating the detrimental effects of early life unhealthy dietary factors on hippocampal-dependent memory function.

BACKGROUND: Gastrointestinal symptoms (GIS) are common after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). However, little is known about frequencies of GIS and their co-occurrence with risky eating behaviors. OBJECTIVES: Compare RYGB and SG on GIS and risky eating behaviors, and test associations between GIS and behaviors. SETTING: Two university hospitals in Northeastern United States. METHODS: RYGB (n = 18) and SG (n = 53) patients completed smartphone-based ecological momentary assessment of GIS and risky eating behaviors at 4 semi-random times daily for 10 days preoperatively and at 3, 6, and 12 months postoperatively. Study objectives were evaluated using generalized linear mixed-effects models. RESULTS: All available data from each assessment were included in the analysis: participant attrition was 18%, 30%, and 38% at 3, 6, and 12 months. All GIS were reduced at 12 months postoperative. Bloating decreased consistently whereas cramping, dehydration, and dumping first increased at 3 to 6 months then decreased to 12 months. Diarrhea, nausea, reflux, and vomiting decreased to 12 months for RYGB, but first increased at 3 to 6 months then decreased to 12 months for SG. Consumption of carbonated and sugar-sweetened beverages, fatty meats, and sweets decreased to 6 months then rebounded at 12 months. Eating past the first sign of fullness, drinking liquids with meals, not starting meals with protein, and fried foods consumption decreased to 6 months and then rebounded for RYGB only at 12 months. Alcohol consumption did not change. Sweets consumption and eating past the first sign of fullness were most consistently associated with GIS for both RYGB and SG patients. CONCLUSION: GIS and risky eating behaviors improved postoperatively, although patterns of change were variable and occasionally differed between RYGB and SG. Pending replication, patients may benefit from intervention to limit risky behaviors that are tailored to their surgery type. (Surg Obes Relat Dis 2021;17:475–483.) 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

The etiology of rotator cuff tearing is likely multifactorial, including a potential genetic predisposition. The purpose of the study was to identify genetic variants associated with rotator cuff tearing utilizing the UK Biobank (UKB) cohort, confirm variants using a separate genetic database, and evaluate tissue expression of genes with associated variants following rotator cuff tearing using RNA sequencing.Genome-wide association study (GWAS): A GWAS was performed using data from UKB with 5701 cases of rotator cuff injury. RNA sequencing analyses: rotator cuff biopsies were obtained from 24 patients with full-thickness rotator cuff tears who underwent arthroscopic rotator cuff repair (cases) and 9 patients who underwent open reduction internal fixation for a proximal humerus fracture (controls). Total RNA was extracted and differential gene expression was measured by RNAseq for genes with variants associated with rotator cuff tearing.The results of the UKB GWAS identified 3 loci that reached genome-wide statistical significance: 2 loci on chromosome 7 in GLCCI1 (rs4725069; P = 5.0E-09) and THSD7A (rs575224171; P = 5.3E-09), and 1 locus on chromosome 2 in ZNF804A (rs775583810; P = 3.9E-09). The association with rotator cuff injury of the GLCCI1 single-nucleotide polymorphism (SNP; rs4725069) was confirmed in the Kaiser Permanente Research Bank cohort (P = .008). Twenty previously reported SNPs in 12 genes were evaluated using summary statistics from the UKB GWAS, which confirmed 3 SNPs in TNC with rotator cuff injury (rs1138545, rs72758637, and rs7021589; all P.0024). Of 17 genes with variants associated with rotator cuff injury (14 previously from literature plus 3 new genes from current UKB GWAS), TIMP2, Col5A1, TGFBR1, and TNC were upregulated (P.001 for all) and THSD7A was downregulated (P = .005) in tears vs. controls in the RNA sequencing data set.The UKB GWAS has identified 3 novel loci associated with rotator cuff tearing (ZNF804A, GLCCI1, THSD7A). Expression of the THSD7A gene was significantly downregulated in rotator cuff tears vs. controls supporting a potential functional role. Three previously reported SNPs in the TNC gene were validated in the UKB GWAS, supporting a role for this gene in rotator cuff tearing. Finally, TIMP2, Col5A1, TGFBR1, and TNC genes were found to have significantly upregulated tissue expression in cases vs. controls supporting a biologic role in tearing for these genes.

Executive cognitive functioning (ECF) and trait impulsivity have long been implicated in risky drinking and alcohol-related problems. However, research on these constructs has developed independently. The present study tested whether two subdomains of adolescent ECF (updating and response inhibition) and adolescent trait impulsivity, considered separately and together, predicted young-adult risky drinking and alcohol-related problems. Data came from the Adolescent/Adult Family Development Project-a longitudinal study of the intergenerational transmission of alcohol use. Alcohol-naive youth ages 11-17 (N = 249) completed three tasks tapping ECF subdomains of updating (letter-number sequencing, matrix span task) and inhibition (immediate memory task) and a self-reported measure of trait impulsivity (UPPS-P). Approximately 7 years later (ages 18-25), participants reported on their drinking behavior (maximum drinks in a day, heavy episodic drinking, alcohol-related problems). We tested whether adolescent ECF and trait impulsivity predicted young-adult drinking outcomes, separately and together. Results showed that poorer adolescent ECF (a latent factor) predicted more maximum drinks in a day (Incidence Rate Ratios [IRR] = 1.27, p = .001) but not young-adult heavy episodic drinking and alcohol-related problems. In contrast, adolescent trait impulsivity predicted all three outcomes: maximum drinks in a day (IRR = 1.34, p < .001), heavy episodic drinking (β = 0.27, p < .001), and alcohol-related problems in young adulthood (IRR = 1.60, p = .001). Results were similar when adolescent ECF and trait impulsivity were considered together in the same model. Findings suggest that adolescent trait impulsivity is a robust predictor of young-adult risky drinking and alcohol-related problems. Adolescent ECF, and specifically response inhibition, may add predictive value over and above trait impulsivity for some alcohol outcomes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

This study was funded by the Medical Research Council, the European Community’s Seventh Framework Program grant [agreement HEALTH-F2-2009-241909 (Project EU-GEI)], São Paulo Research Foundation (grant 2012/0417-0), the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London, the NIHR BRC at University College London and the Wellcome Trust (grant 101272/Z/12/Z)., Tripoli, G., Quattrone, D., Ferraro, L., Gayer-Anderson, C., Rodriguez, V., La Cascia, C., La Barbera, D., Sartorio, C., Seminerio, F., Tarricone, I., Berardi, D., Szöke, A., Arango, C., Tortelli, A., Llorca, P.-M., De Haan, L., Velthorst, E., Bobes, J., Bernardo, M., Sanjuán, J., Santos, J.L., Arrojo, M., Del-Ben, C.M., Menezes, P.R., Selten, J.-P., Jones, P.B., Jongsma, H.E., Kirkbride, J.B., Lasalvia, A., Tosato, S., Richards, A., O'donovan, M., Rutten, B.P.F., Os, J.V., Morgan, C., Sham, P.C., Murray, R.M., Murray, G.K., Di Forti, M.