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Objectives: To determine the association between closed suction drainage and postoperative infection in patients with tibial plateau or pilon fractures. Secondarily, this study assessed if intrawound vancomycin powder modified the association of closed surgical drains with infection., Methods: Design: Secondary analysis of the Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial (VANCO) trial., Setting: 36 academic trauma centers., Patient Selection Criteria: All patients with high-risk tibia fractures (OTA/AO classification 41B/C or 43B/C) from the VANCO trial were considered. Closed suction drains were placed based on the treating surgeon's discretion. Patients were randomly assigned to received 1-gram intrawound vancomycin powder in the surgical wound at definitive fixation or the standard infection prevention protocol at each center.Outcome Measures and Comparisons: Deep surgical site infection (SSI) within 6 months. Comparisons were made between patients treated with and without drains. Subgroup analysis also examined the effect of drains in patients with and without intrawound vancomycin powder., Results: Of the 978 study patients, 197 (20%) were treated with drains. Deep infection rates did not significantly differ between patients with or without surgical drains (8% versus 8%, p=0.88). However, intrawound vancomycin powder significantly modified the association of surgical drains on deep SSI (interaction p=0.048). Specifically, patients with drains but no vancomycin powder had the highest deep infection rate (13%; 95% CI, 6% to 19%). When vancomycin powder was used in addition to a drain, deep SSI rates were reduced by 10% (95% CI, 2% to 17%, p=0.01)., Conclusions: This study suggests that closed suction drains after operative fixation of high-risk tibia fractures may not be associated with deep infection in general. However, a secondary analysis raises the possibility that drains are associated with reduced deep infection rates if topical vancomycin powder is used but associated with increased infection rates if vancomycin powder is not used., Level of Evidence: Level III., Competing Interests: Potential Conflicts of Interest and Funding Sources: The authors report no actual or potential conflicts of interest. No external funding was received for this work. Work on the original VANCO study was supported by United States Department of Defense CDMRP award # W81XWH-10-2-0134. The original sponsor had no role in the design or conduct of the trial; the collection, management, analysis, or interpretation of this data; or the preparation, review, or approval of this manuscript for submission., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The impact of cannabis on cognitive and psychomotor function is important to understand, given the role of the endocannabinoid system in these critical processes. The literature has shown robust acute negative effects of cannabis on cognition and psychomotor skills during intoxication, and to a lesser degree, persisting effects following short-term abstinence up to 4 weeks. However, whether these decrements resolve after long-term cessation of use remains unclear. We evaluated cognitive and psychomotor function in 31 adults with current cannabis use during unrestricted use (UNR) and after a 3-day abstinence (RES), 23 adults with former cannabis use (> 90 days abstinent; FU), and 58 nonusing controls (CON) using the cognition and motor batteries of the National Institutes of Health Toolbox. Linear mixed models showed no significant differences in cognitive and motor performance between UNR, RES, and FU groups. Group effects emerged such that CON outperformed UNR on the Oral Reading Recognition Test, and CON outperformed both UNR and RES on the Picture Vocabulary Test. In terms of psychomotor function, FU, RES, and UNR performed better than CON on the Grip Strength Test. In this comprehensive examination of cognitive and psychomotor performance in adults with cannabis use with 3 days to > 90 days of abstinence, our results indicated that the cognitive impacts of chronic, heavy cannabis use are observable during short-term abstinence but remit after > 90 days of abstinence. This highlights widespread impacts of cannabis use abstinence across cognitive and psychomotor domains. Future studies are needed to evaluate whether these effects are also observable with use reduction, as opposed to abstinence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Aim: Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. However, the neurobiological mechanisms underpinning Reserve are not fully understood. In this regard, a noradrenergic (NA) theory of cognitive reserve (Robertson, 2013) has proposed that the upregulation of NA system might be a key factor for building reserve and resilience to neurodegeneration because of the neuroprotective role of NA across the brain. PA elicits an enhanced catecholamine response, in particular for NA. By increasing physical commitment, a greater amount of NA is synthetised in response to higher oxygen demand. More physically trained individuals show greater capabilities to carry oxygen resulting in greater Vo 2 max - a measure of oxygen uptake and physical fitness (PF)., Methods: We hypothesized that greater Vo 2 max would be related to greater Locus Coeruleus (LC) MRI signal intensity. In a sample of 41 healthy subjects, we performed Voxel-Based Morphometry analyses, then repeated for the other neuromodulators as a control procedure (Serotonin, Dopamine and Acetylcholine)., Results: As hypothesized, greater Vo 2 max related to greater LC signal intensity, and weaker associations emerged for the other neuromodulators., Conclusion: This newly established link between Vo 2 max and LC-NA system offers further understanding of the neurobiology underpinning Reserve in relationship to PA. While this study supports Robertson's theory proposing the upregulation of the NA system as a possible key factor building Reserve, it also provides ground for increasing LC-NA system resilience to neurodegeneration via Vo 2 max enhancement., (© 2024 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Introduction: Multiplanar mesh plating of patella fractures has become more popular in recent years. It was the goal of this study to compare the biomechanical stability of cannulated screw with anterior tension band to multiplanar mesh plating for fixation of transverse patella fractures in cadaver specimens., Materials and Methods: Eight matched pairs of fresh frozen cadaveric knees were obtained and soft tissues dissected leaving the extensor mechanism, joint capsule, and retinaculum intact. Transverse fractures were created at the mid-portion of the patella. For each pair, one specimen was repaired using cannulated screws with anterior tension band, and the second was repaired using multiplanar mesh plating. Each specimen underwent cyclic extension loading with loads increasing by 1.1 kg after every 50 cycles. Interfragmentary displacement was measured at the end of each interval at both 5° and 45° of knee flexion angle, with fixation failure defined by >2 mm displacement., Results: The specimens fixed with multiplanar mesh plating survived more cycles and higher loads than the specimens fixed with cannulated screws with anterior tension band (p = 0.011 comparing survival plots). After 150 cycles of extension loading, 3 of 8 of the specimens fixed with screws/tension band had failed, whereas none of the mesh plated specimens had failed. After 400 cycles, 7 of 8 of the screws/tension band had failed, whereas half of the mesh plated specimens had failed., Conclusions: While a more technically challenging and expensive technique, mesh plating for patella fractures appears to offer greater durability than traditional cannulated screw with tension banding., Competing Interests: Declaration of competing interest Implants for the study were provided by Johnson & Johnson Depuy Synthes. Additional support provided by National Institute of Biomedical Imaging and Bioengineering award R01EB029207, (Copyright © 2024. Published by Elsevier Ltd.)

Background: Predicting future brain health is a complex endeavor that often requires integrating diverse data sources. The neural patterns and interactions identified through neuroimaging serve as the fundamental basis and early indicators that precede the manifestation of observable behaviors or psychological states., New Method: In this work, we introduce a multimodal predictive modeling approach that leverages an imaging-informed methodology to gain insights into future behavioral outcomes. We employed three methodologies for evaluation: an assessment-only approach using support vector regression (SVR), a neuroimaging-only approach using random forest (RF), and an image-assisted method integrating the static functional network connectivity (sFNC) matrix from resting-state functional magnetic resonance imaging (rs-fMRI) alongside assessments. The image-assisted approach utilized a partially conditional variational autoencoder (PCVAE) to predict brain health constructs in future visits from the behavioral data alone., Results: Our performance evaluation indicates that the image-assisted method excels in handling conditional information to predict brain health constructs in subsequent visits and their longitudinal changes. These results suggest that during the training stage, the PCVAE model effectively captures relevant information from neuroimaging data, thereby potentially improving accuracy in making future predictions using only assessment data., Comparison With Existing Methods: The proposed image-assisted method outperforms traditional assessment-only and neuroimaging-only approaches by effectively integrating neuroimaging data with assessment factors., Conclusion: This study underscores the potential of neuroimaging-informed predictive modeling to advance our comprehension of the complex relationships between cognitive performance and neural connectivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objective: To determine whether intrawound vancomycin changes the bacteriology of surgical site infection pathogens and investigate the emergence of antibiotic-resistant pathogens., Design: Secondary analysis of phase III, prospective, randomized clinical trial., Setting: Thirty-six US trauma centers., Patient Selection Criteria: Patients who became infected after fixation of tibial plateau or pilon fracture., Outcome Measures and Comparisons: Pathogen types and bacterial susceptibilities as determined from routine clinical culture in the operating room., Results: Seventy-four patients were studied who were 67.5% male with a mean age of 48.6 years. A lower proportion of gram-positive cocci was observed in the vancomycin powder compared with the standard-of-care group (3.7% vs. 8.0%, P = 0.01). Methicillin-resistant Staphylococcus aureus infection incidence was comparable in both the vancomycin powder and the standard-of-care groups, but rates of methicillin-susceptible S. aureus infections were lower in the treatment group (1.4% vs. 4.8%, P = 0.01). The incidence of coagulase-negative Staphylococci and gram-negative rod infections were similar in both groups. There was no significant difference in susceptibilities between groups in rates of vancomycin-resistant enterococcus., Conclusions: Topical vancomycin powder decreases the likelihood of gram-positive infections consistent with the biologic activity of vancomycin. Fewer methicillin-susceptible S. aureus and coagulase-negative Staphylococci infections were observed in the group treated with vancomycin powder. An effect of vancomycin powder on methicillin-resistant S. aureus infection risk was not detected given the low incidence in both the intrawound vancomycin and the standard-of-care groups. There was no emergence of gram-negative rod infections or increased resistance patterns observed. Use of topical vancomycin powder does not seem to produce infections in these patients with greater antibiotic resistance than would have occurred without its use., Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dynamic compression plating is a fundamental type of bone fracture fixation used to generate interfragmentary compression. The goal of this study was to investigate the mechanics of the surgical application of these plates, specifically how plate prebend, screw location, fracture gap, and applied torque influence the resulting compressive pressures., Methods: Synthetic bones with transverse fractures were fixed with locking compression plates. One side of the fracture was fixed with locking screws. On the other side of the fracture, a nonlocking screw was inserted eccentrically to induce interfragmentary compression. A pressure mapping sensor within the fracture gap was used to record the resulting pressure distribution. Plate prebends of 0 mm, 1.5 mm, and 3 mm were tested. Three locations of the eccentric screw, four levels of screw torque, and two initial fracture gap conditions also were tested., Findings: With increasing plate prebend, fracture compression pressures shifted significantly toward the far cortex; however, compression force decreased (P < 0.05). The 1.5 mm prebend plate resulted in the greatest contact area. Increasing screw torque generally resulted in greater fracture compression force. The introduction of a 1 mm fracture gap at the far cortex prior to dynamic compression resulted in little or no fracture compression., Interpretation: The model showed that increasing plate prebend results in an increasing shift of fracture compression pressures toward the far cortex; however, this is accompanied by decreases in compressive force. Initial fracture gaps at the far cortex can result in little or no compression., Competing Interests: Declaration of competing interest J.S. Reid is a product development consultant with Depuy Synthes, a product development consultant with Osteocentric, and a stockholder with ROMtech. G.S. Lewis is a co-investigator on research funded by Arthrex Inc. For the remaining authors no conflicts are declared., (Copyright © 2023. Published by Elsevier Ltd.)

The goal of precision brain health is to accurately predict individuals' longitudinal patterns of brain change. We trained a machine learning model to predict changes in a cognitive index of brain health from neurophysiologic metrics. A total of 48 participants (ages 21-65) completed a sensorimotor task during 2 functional magnetic resonance imaging sessions 6 mo apart. Hemodynamic response functions (HRFs) were parameterized using traditional (amplitude, dispersion, latency) and novel (curvature, canonicality) metrics, serving as inputs to a neural network model that predicted gain on indices of brain health (cognitive factor scores) for each participant. The optimal neural network model successfully predicted substantial gain on the cognitive index of brain health with 90% accuracy (determined by 5-fold cross-validation) from 3 HRF parameters: amplitude change, dispersion change, and similarity to a canonical HRF shape at baseline. For individuals with canonical baseline HRFs, substantial gain in the index is overwhelmingly predicted by decreases in HRF amplitude. For individuals with non-canonical baseline HRFs, substantial gain in the index is predicted by congruent changes in both HRF amplitude and dispersion. Our results illustrate that neuroimaging measures can track cognitive indices in healthy states, and that machine learning approaches using novel metrics take important steps toward precision brain health., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To estimate the generalizability of treatment effects observed in the VANCO trial to a broader population of patients with tibial plateau or pilon fractures., Methods: Design and Setting: Clinical trial data from 36 United States trauma centers and Trauma Quality Programs registry data from more than 875 Level I-III trauma centers in the United States and Canada.Patient Selection Criteria: Patients enrolled in the VANCO trial treated with intrawound vancomycin powder from January 2015 to June 2017 and 31,924 VANCO-eligible TQP patients admitted in 2019 with tibial plateau and pilon fractures.Outcome Measure and Comparisons: Deep surgical site infection and gram-positive deep surgical site infection estimated in the TQP sample weighed by the inverse probability of trial participation., Results: The 980 patients in the VANCO trial were highly representative of 31,924 TQP VANCO-eligible patients (Tipton generalizability index 0.96). It was estimated that intrawound vancomycin powder reduced the odds of deep surgical infection by odds ratio (OR) = 0.46 (95% confidence interval [CI] 0.25-0.86) and gram-positive deep surgical infection by OR = 0.39 (95% CI, 0.18-0.84) within the TQP sample of VANCO-eligible patients. For reference, the trial average treatment effects for deep surgical infection and gram-positive deep surgical infection were OR = 0.60 (95% CI, 0.37-0.98) and OR = 0.44 (95% CI, 0.23-0.80), respectively., Conclusions: This generalizability analysis found that the inferences of the VANCO trial generalize and might even underestimate the effects of intrawound vancomycin powder when observed in a wider population of patients with tibial plateau and pilon fractures., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The workplace typically affords one of the longest periods for continued brain health growth. Brain health is defined by the World Health Organization (WHO) as the promotion of optimal brain development, cognitive health, and well-being across the life course, which we expanded to also include connectedness to people and purpose. This work was motivated by prior work showing individuals, outside of an aggregate setting, benefitted from training as measured by significant performance gains on a holistic BrainHealth Index and its factors (i.e., clarity, connectedness, emotional balance). The current research was conducted during the changing remote work practices emerging post-pandemic to test whether a capacity-building training would be associated with significant gains on measures of brain health and components of burnout. The study also tested the influence of utilization of training modules and days in office for individuals to inform workplace practices., Methods: We investigated whether 193 individuals across a firm's sites would improve on measures of brain health and burnout from micro-delivery of online tactical brain health strategies, combined with two individualized coaching sessions, and practical exercises related to work and personal life, over a six-month period. Brain health was measured using an evidenced-based measure (BrainHealth™ Index) with its components (clarity, connectedness, emotional balance) consistent with the WHO definition. Burnout was measured using the Maslach Burnout Inventory Human Services Survey. Days in office were determined by access to digital workplace applications from the firm's network. Regression analyses were used to assess relationships between change in BrainHealth factors and change in components of the Maslach Burnout Inventory., Results: Results at posttest indicated that 75% of the individuals showed gains on a composite BrainHealth Index and across all three composite factors contributing to brain health. Benefits were directly tied to training utilization such that those who completed the core modules showed the greatest gains. The current results also found an association between gains on both the connectedness and emotional balance brain health factors and reduced on burnout components of occupational exhaustion and depersonalization towards one's workplace. We found that fewer days in the office were associated with greater gains in the clarity factor, but not for connectedness and emotional balance., Discussion: These results support the value of a proactive, capacity-building training to benefit all employees to complement the more widespread limited offerings that address a smaller segment who need mental illness assistance programs. The future of work may be informed by corporate investment in focused efforts to boost collective brain capital through a human-centered, capacity-building approach. Efforts are underway to uncover the value of better brain health, i.e., Brainomics© - which includes economic, societal, and individual benefits., Competing Interests: SuC and UN are employed by HKS Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zientz, Spence, Chung, Nanda and Chapman.)

Background: The cognitive training Strategic Memory Advanced Reasoning Training (SMART) has been shown to improve symptoms of depression, anxiety, and stress when completed using in-person delivery, but mental health outcomes have not yet been studied for online delivery of SMART., Methods: Data was analyzed from 145 generally healthy adults participating in the BrainHealth Project pilot study who had access to 12 weeks of online self-paced SMART and self-reported mental health symptoms on the Depression Anxiety Stress Scale (DASS-21) pre- and post-training. We utilized linear models to examine the change in self-reported symptoms of depression, anxiety, and stress following the 12-week training period and to explore the influence of age, gender, and education on changes in symptomatology. Data from 44 participants who completed a follow-up DASS-21 6 months after completing SMART was used to explore the lasting impact of the training., Results: Improvements in depression, anxiety, and stress symptoms were observed following online SMART, evidenced by a significant decrease in self-reported symptoms on the DASS-21. Improvement in self-reported mental health symptomatology was maintained or continued to improve 6-month post-training. No significant effect of gender was observed, but findings motivate additional exploration of the effects of education and age., Conclusion: Online SMART should be considered a low-cost, high-impact approach for supporting public mental health for generally healthy adults., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Neural-vascular coupling (NVC) is the process by which oxygen and nutrients are delivered to metabolically active neurons by blood vessels. Murine models of NVC disruption have revealed its critical role in healthy neural function. We hypothesized that, in humans, aging exerts detrimental effects upon the integrity of the neural-glial-vascular system that underlies NVC. To test this hypothesis, calibrated functional magnetic resonance imaging (cfMRI) was used to characterize age-related changes in cerebral blood flow (CBF) and oxygen metabolism during visual cortex stimulation. Thirty-three younger and 27 older participants underwent cfMRI scanning during both an attention-controlled visual stimulation task and a hypercapnia paradigm used to calibrate the blood-oxygen-level-dependent signal. Measurement of stimulus-evoked blood flow and oxygen metabolism permitted calculation of the NVC ratio to assess the integrity of neural-vascular communication. Consistent with our hypothesis, we observed monotonic NVC ratio increases with increasing visual stimulation frequency in younger adults but not in older adults. Age-related changes in stimulus-evoked cerebrovascular and neurometabolic signal could not fully explain this disruption; increases in stimulus-evoked neurometabolic activity elicited corresponding increases in stimulus-evoked CBF in younger but not in older adults. These results implicate age-related, demand-dependent failures of the neural-glial-vascular structures that comprise the NVC system., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Computer-assisted hexapod ring fixation systems (HRF) are used for multiple conditions and in very diverse patient populations. This study analyzes perioperative outcomes following HRF application based on patient etiology and clinical presentation., Methods: Data from patients in the Premier Hospital Billing Database between 2007-2019 undergoing HRF application were analyzed for the duration of patients' hospitalizations. Patients were grouped based on etiology: acquired deformity, arthrosis, congenital deformity, deep infection, infected nonunion, fracture, nonunion, and other post-operative complications. Demographics, comorbidities, operating room time (ORT), length of stay (LOS), peri-operative complications, and hospital costs were estimated using generalized linear models. Logistic regression evaluated factors associated with peri-operative complications., Results: One thousand eight hundred eighteen patients (average age: 46.9, standard deviation (SD) (19.6) - 38.9% female) were included in the study, and included 72% fracture cases, 9.6% deep infection, 10.2% deformity (acquired: 5.9%, congenital: 4.3%), 4.2% nonunions, 2% arthrosis and 1.4% other sequelas from prior fractures. Comorbidities varied across diagnosis categories and age, 40% adults and 86% pediatric had no comorbidities. Pediatric cases mostly suffered from obesity (16.1%) and pulmonary disease (10.7%). Complicated diabetes was present in 45.9% of arthropathy and 34.3% of deep infection patients. ORT, LOS and inflation-adjusted hospital costs for all patients averaged 277.7 min (95% Confidence interval (CI): 265.1-290.3), 7.07 days (95% CI: 6.6-7.5) and $41,507 (95%CI: $39,728-$43,285), respectively, but were highest in patients with deep infection (ORT: 369 min (95%CI: $321.0-$433.8); LOS: 14.4 days (95%CI: $13.7-$15.1); Cost: $54,666 (95%CI: $47,960-$63,553)). The probability of having an intraoperative complication averaged 35% (95%CI: 28%-43%) in adult patients with deep infection vs 7% (95%CI: 2%-20%) in pediatric cases treated for congenital deformity. The risk for intraoperative complications was mostly associated with preexisting comorbidities, an Elixhauser > 5 was the most predictive risk factor for complications (odds ratios: 4.53 (95%CI: 1.71-12.00, p = 0.002)., Conclusions: There is important heterogeneity among HRF patients. Adults with HRF for fracture, deep infection and arthrosis are at far greater risk for peri-operative complications vs. patients with deformity, especially pediatric deformity cases, mostly due to existing comorbidities and age. Device-specific HRF clinical studies cannot be generalized beyond their exact patient population., (© 2022. The Author(s).)

Amnestic mild cognitive impairment (aMCI) is marked by episodic memory deficits, which can be used to classify individuals into early MCI (EMCI) and late MCI (LMCI). Although mounting evidence suggests that individuals with aMCI have additional cognitive alterations including deficits in cognitive control, few have examined if EMCI and LMCI differ on processes other than episodic memory. Using a semantic Go/NoGo task, we examined differences in cognitive control between EMCI and LMCI on behavioral (accuracy and reaction time) and neural (scalp-recorded event-related oscillations in theta and alpha band) measures. Although no behavioral differences were observed between the EMCI and LMCI groups, differences in neural oscillations were observed. The LMCI group had higher theta synchronization on Go trials at central electrodes compared to the EMCI group. In addition, the EMCI group showed differences in theta power at central electrodes and alpha power at central and centro-parietal electrodes between Go and NoGo trials, while the LMCI group did not exhibit such differences. These findings suggest that while behavioral differences may not be observable, neural changes underlying cognitive control processes may differentiate EMCI and LMCI stages and may be useful to understand the trajectory of aMCI in future studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Multiplanar external fixation systems that employ software-assisted deformity correction consist of rings connected by angled struts, defined as hexapod ring fixators (HRF). Costs and outcomes associated with the application of HRFs are not well documented. This study was designed to provide a nationwide baseline understanding of the clinical presentation, risks, outcomes and payer costs, and healthcare resource utilization (HCU) of patients requiring application of an HRF, from the day of, and up to 2 years, post-application., Methods: Patients with HRF application ("index") between 2007 and 2019 within the IBM Marketscan® Commercial Claims database were identified and categorized based on diagnosis: acquired deformity, arthropathy, congenital deformity, deep infection, nonunion, fracture, and other post-operative fracture sequelae. Demographics, comorbidities at index, complications post-index, HCU, and payments were analyzed. Payments were estimated using a generalized linear model and were adjusted for inflation to the 2020 consumer price index. Rates of deep infection and amputation were estimated up to 2 years post-index using Poisson regressions, and risk factors for each were estimated using logistic regression models., Results: Six hundred ninety-five patients were included in our study (including 219 fractures, 168 congenital deformities, 68 deep infections, 103 acquired deformities). Comorbidities at index were significantly different across groups: less than 2% pediatrics vs 18% adults had 3 or more comorbidities, < 1% pediatric vs 29% adults had diabetes. Index payments ranged from $39,250-$75,350, with 12-months post-index payments ranging from $14,350 to $43,108. The duration of the HRF application ranged from 96 days to 174 days. Amputation was observed in patients with deep infection (8.9, 95% confidence interval (CI): 3.2-23.9%), nonunion (5.0, 95%CI: 1.6-15.4%) or fracture (2.7, 95%CI: 0.9-7.6%) at index. Complicated diabetes was the main predictor for deep infection (odds ratio (OR): 5.14, 95%CI: 2.50-10.54) and amputation (OR: 5.26, 95%CI: 1.79-15.51)., Conclusions: Findings from this longitudinal analysis demonstrate the significant heterogeneity in patients treated with HRF, and the wide range in treatment intensity, payments, and outcomes. Risks for deep infection and amputation were primarily linked to the presence of complicated diabetes at the time of HRF application, suggesting a need for careful management of comorbid chronic conditions in patients requiring HRF for orthopedic care., (© 2021. The Author(s).)

Introduction: In the surgical fixation of fractures, proper biomechanical stability is key in preventing clinical complications including poor fracture healing, residual deformity, loss of fixation, or implant failure. Stability is largely influenced by treatment decisions made by the surgeon. The interplay of surgeon-controlled variables and their effect on the three-dimensional (3D) biomechanics of a fracture fixation construct are often not intuitive, and current training methods do not facilitate a deep understanding of these interactions., Methods: A simulation software interface, FracSim, was developed. FracSim is built on a large precomputed library of finite element simulations. The software allows a surgeon to make adjustments to a virtual fracture fixation construct/weight-bearing plan and immediately visualize how these changes affect 3D biomechanics, including implant stress and fracture gap strain, important for clinical success. Twenty-one orthopaedic residents completed an instructor-led educational session with FracSim focused on bridge plating. Subjects completed pretests and posttests of knowledge of biomechanical concepts and a questionnaire., Results: Subjects scored a mean of 5.6/10 on the pretest of biomechanical knowledge. Senior residents scored better than junior residents (P = 0.04). After the educational session with FracSim, residents improved their test scores to a mean of 8.0/10, with a significant improvement (P < 0.001). Questionnaire scores indicated that subjects believed that FracSim had realistic implants, constructs, and motions and that training with FracSim was purposeful, desirable, efficient, fun, and useful for enhancing the understanding of fracture fixation biomechanics., Discussion: This new type of simulation software enables interactive visualization of 3D fracture fixation biomechanics. Limitations of this study include lack of a control group undergoing traditional education and lack of a delayed posttest to assess retention. FracSim may provide an effective and engaging way to promote a deeper understanding of biomechanical concepts in the orthopaedic learner., (Copyright © 2021 by the American Academy of Orthopaedic Surgeons.)

Respiration rate (RR) dynamics entrains brain neural networks. RR differences between mild cognitive impairment (MCI) and Alzheimer's disease (AD) in response to oral appliance therapy (OAT) are unknown. This pilot study investigated if RR during stable sleep shows a relationship to pathological severity in subjects with MCI and AD who snore and if RR is influenced following stabilization of the upper airway using OAT. The study cohort was as follows: cognitively normal (CN; n = 14), MCI ( n = 14) and AD ( n = 9); and a sub-population receiving intervention, CN ( n = 5), MCI ( n = 7), AD ( n = 6) subjects. The intervention used was an oral appliance plus a mouth shield (Tx). RR maximum (max) rate (breaths/minute) and RR fluctuation during 2116 stable sleep periods were measured. The Montreal cognitive assessment (MoCA) was administered before and after 4 weeks with Tx. Baseline data showed significantly higher RR fluctuation in CN vs. AD ( p < 0.001) but not between CN vs. MCI ( p = 0.668). Linear mixed model analysis indicated Tx effect ( p = 0.008) for RR max. Tx after 4 weeks lowered the RR-max in MCI ( p = 0.022) and AD ( p < 0.001). Compared with AD RR max, CN ( p < 0.001) and MCI ( p < 0.001) were higher with Tx after 4 weeks. Some MCI and AD subjects improved executive and memory function after 4 weeks of Tx.

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., Competing Interests: All ICMJE Conflict of Interest Forms for authors and are on file with the publication and can be viewed on request: Joseph T. Patterson: AOTrauma North America: research support. Keisuke Ishii: Naradewa: research support. C. B. Jones: Arizona Orthopaedic Society: board or committee member, Dignity Health: employee, Journal of Bone and Joint Surgery—American: Editorial or governing board, Journal of Orthopaedics and Traumatology: Editorial or governing board, Lippincott: IP royalties, Orthopaedic Trauma Association OTA—grant: Research support, OsteConcentric: Paid consultant, IP royalties, Stryker: Paid consultant; Paid presenter or speaker. R. K. Leighton: AAOS: Board or committee member, Canadian Orthopaedic Association: board or committee member, DePuy, A Johnson & Johnson Company: Other financial or material support; paid presenter or speaker, Etex: paid consultant, Smith & Nephew: other financial or material support; paid presenter or speaker, Stryker: other financial or material support; paid presenter or speaker, Synthes: paid presenter or speaker; research support, Zimmer: paid presenter or speaker. T. Miclau: AO Foundation: board or committee member, Arquos: paid consultant; stock or stock Options, Baxter: research support, Bone Therapeutics: paid consultant, Globus Medical: other financial or material support, Inman Abbott Society: board or committee member, International Combined Orthopaedic Research Societies: board or committee member, International Orthopaedic Trauma Association: board or committee member, KCI: other financial or material support, NXTSENS: paid consultant, Orthopaedic Research Society: board or committee member, Orthopaedic Trauma Association: board or committee member, Osteosynthesis and Trauma Care Foundation: board or committee member, San Francisco General Hospital Foundation: board or committee member, Stryker: other financial or material support, Surrozen: paid consultant, Synthes: paid consultant. B. H. Mullis: Indiana Orthopaedic Society: board or committee member, KCI: paid consultant, Orthopaedic Trauma Association: Board or committee member. W. T. Obremskey: Journal of Bone and Joint Surgery - American: editorial or governing board, Journal of Orthopaedic Trauma: editorial or governing board, Journal of the American Academy of Orthopaedic Surgeons: editorial or governing board, Orthopaedic Trauma Association: board or committee member, Southeastern Fracture Consortium: board or committee member. R. F. Ostrum: Bioventus: paid consultant; paid presenter or speaker, Journal of Orthopaedics and Traumatology: editorial or governing board, SLACK Incorporated: publishing royalties, financial, or material support, Wolters Kluwer Health—Lippincott Williams & Wilkins: Editorial or governing board; publishing royalties, financial, or material support. J. S. Reid: Clinical Orthopaedics and Related Research: editorial or governing board, Journal of Orthopaedics and Traumatology: editorial or governing board, Limb Lengthening and Reconstruction Society: board or committee member, ROM3 now ROMtech: Stock or stock Options, Smith & Nephew: paid consultant, Synthes: paid consultant; research support, Zimmer: research support. Andrew H. Schmidt: ActivOrtho: stock or stock options, Conventus Orthopaedics: stock or stock options, Conventus Orthopedics: paid consultant, Enova Illumination, Inc.: stock or stock options, Epien: stock or stock options, Epix VAN: stock or stock options, JBJS Essential Surgical Techniques: editorial or governing board, Journal of Knee Surgery: editorial or governing board, Journal of Orthopaedic Trauma: editorial or governing board, Abbott Medical: paid consultant (spouse), Thieme, Inc.: publishing royalties, financial or material support, Twin Star Medical: stock or stock options. David C. Teague: Journal of Orthopaedic Trauma: Editorial or governing board, Orthopaedic Trauma Association: board or committee member. P. Tornetta III: Journal of Orthopaedic Trauma: editorial or governing board, Smith & Nephew: IP royalties Wolters Kluwer Health—Lippincott Williams & Wilkins: publishing royalties, financial or material support. S. Morshed: Orthopaedic Trauma Association: board or committee member. The remaining authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Fracture fixation aims to provide stability and promote healing, but remains challenging in unstable and osteoporotic fractures with increased risk of construct failure and nonunion. The first part of this article reviews the clinical motivation behind finite element analysis of fracture fixation, its strengths and weaknesses, how models are developed and validated, and how outputs are typically interpreted. The second part reviews recent modeling studies of the femur and proximal humerus, areas with particular relevance to fragility fractures., Recent Findings: There is some consensus in the literature around how certain modeling aspects are pragmatically formulated, including bone and implant geometries, meshing, material properties, interactions, and loads and boundary conditions. Studies most often focus on predicted implant stress, bone strain surrounding screws, or interfragmentary displacements. However, most models are not rigorously validated. With refined modeling methods, improved validation efforts, and large-scale systematic analyses, finite element analysis is poised to advance the understanding of fracture fixation failure, enable optimization of implant designs, and improve surgical guidance., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: (1) Evaluate intentional temporary limb deformation for closure of soft-tissue defects as a reconstruction strategy in open tibia fractures and (2) analyze the deformity parameters required for such reconstruction., Design: Multicenter retrospective cohort., Setting: Level I trauma center., Patients/participants: Nineteen patients 18 years of age and older at the time of initial trauma, with a Gustilo-Anderson type IIIB or IIIC open tibia fracture treated with hexapod external fixation and intentional bony deformity created to facilitate soft-tissue closure., Intervention: Intentional limb deformation for soft-tissue closure, followed by gradual correction with a hexapod external fixator., Outcome Measurements: Radiographic healing, radiographic assessment of limb alignment, and functional and bony Application of the Method of Ilizarov Group score., Results: The average age was 45.3 (20-70), and 79% of patients were men. The most common mechanism of injury was motor vehicle accidents. The distal 1 of 5 of the tibia was the most common fracture location, with 37% of these involving the articular surface at the plafond. After wound closure, deformity correction was initiated after 30 days on average. Varus and apex posterior were the most common initial deformity required for primary soft-tissue closure. Bony and functional Application of the Method of Ilizarov Group outcomes were good or excellent in 94% of patients., Conclusion: Intentional deformation followed by a gradual correction can be an effective strategy to obtain bone union and soft-tissue coverage in certain open fractures. This technique, in essence, converts these injuries from type IIIB to IIIA. This strategy obviates the need for flap coverage and results in satisfactory outcomes., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Positive psychiatry offers an unique approach to promote brain health and well-being in aging populations. Minimal interventions through behavioral activation to promote wellness are increasingly available using self-guided apps, yet little is known about the effectiveness of app technology or the difference between clinician-supported behavioral activation versus self-guided app methodologies., Objectives: Investigate the difference in users and outcomes between two methods of the Fountain of Health (FoH) positive psychiatry intervention for behavioral activation to promote brain health and well-being: (1) clinician-assisted and (2) independent app use for behavioral self-management., Design and Setting: As part of a larger knowledge translation intervention in positive psychiatry, two specific methods of a behavioral activation intervention were retrospectively compared., Participants: Two subsets of patients were compared; 254 clinician-assisted patients; 333 independent app users., Intervention: A minimal positive psychiatry intervention in frontline care using the FoH health and behavior change clinical tools., Measurements: Main outcomes were changes in psychological (health and resilience, well-being scores) and behavioral indices (goal attainment, items of goal SMART-ness). User profiles (age, sex and completion rates) were also compared., Results: Clinician-assisted patients were more likely to be male, older, and have lower health and resilience scores at baseline. Clinician-assisted patients had notably higher completion rates (99.2% vs. 10.8%). Psychological outcomes (improved health and resilience, and well-being) were similar regardless of intervention method for those who completed the intervention. Behavioral outcomes revealed clinician-assisted patients set goals that better adhered to key goal-setting items., Conclusions: Clinician-patient relationships appear to be an important factor for intervention completion and behavioral outcomes, while further exploration of best practices for intervention completion using health apps in clinical practice is needed. A preliminary goal-setting methodology for effective behavioral activation, to promote brain health and wellness, is given.

Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist., Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections., Design, Setting, and Participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers., Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder., Main Outcomes and Measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence., Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections., Conclusions and Relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin., Trial Registration: ClinicalTrials.gov Identifier: NCT02227446.

Subclinical bacterial infections (biofilms) are strongly implicated in breast augmentation failure due to capsular contracture, and while these infections are generally ascribed to common skin commensals, this remains largely unsubstantiated through robust cultivation independent analyses. To determine capsule biofilm microbial community compositions, we employed amplicon sequencing of the 16S rRNA gene using DNA extracted from breast implant capsule samples. These cultivation independent analyses revealed that capsule associated biofilms are more diverse than canonical single-species infections, but have relatively low diversity (~ <100 species) compared to many host-associated microbial communities. In addition to taxa commonly associated with capsular contracture, the biofilms analyzed comprised a number of taxa that escaped detection in cultivation-dependent work. We have also isolated several key taxa identified through the culture-independent analyses. Together our analyses reveal that capsule biofilms are more diverse than cultivation studies suggest and can be heterogeneous within an individual capsule, between breasts of the same patient, across similar implant types, and over a range in severity of contracture. The complex nature of these communities requires further study across a broader suite of patients in addition to higher resolution analyses including metagenomics to better assess the fundamental role of microorganisms in capsular contracture., Competing Interests: NC and PL are also employed at Skin Works and Vancouver Plastic Surgery, respectively. Skin Works and Vancouver Plastic Surgery provided income for NC and PL as well as matching funds for NSERC engage grant 488438. We have no competing interests and our commercial affiliations do not alter our adherence to PLOS One policies on sharing data and materials.

Introduction: Brain health is neglected in public health, receiving attention after something goes wrong. Neuroplasticity research illustrates that preventive steps strengthen the brain's component systems; however, this information is not widely known. Actionable steps are needed to scale proven population-level interventions. Objectives: This pilot tested two main objectives: (1) the feasibility/ease of use of an online platform to measure brain health, deliver training, and offer virtual coaching to healthy adults and (2) to develop a data driven index of brain health. Methods: 180 participants, ages 18-87, enrolled in this 12-week pilot. Participants took a BrainHealth Index™ (BHI), a composite of assessments encompassing cognition, well-being, daily-life and social, pre-post training. Participants engaged in online training with three coaching sessions. We assessed changes in BHI, effects of training utilization and demographics, contributions of sub-domain measures to the BHI and development of a factor analytic structure of latent BrainHealth constructs. Results: The results indicated that 75% of participants showed at least a 5-point gain on their BHI which did not depend on age, education, or gender. The contribution to these gains were from all sub-domains, including stress, anxiety and resilience, even though training focused largely on cognition. Some individuals improved due to increased resilience and decreased anxiety, whereas others improved due to increased innovation and social engagement. Larger gains depended on module utilization, especially strategy training. An exploratory factor analytic solution to the correlation matrix of online assessments identified three latent constructs. Discussion/Conclusion: This pilot study demonstrated the efficacy of an online platform to assess changes on a composite BrainHealth Index and efficacy in delivering training modules and coaching. We found that adults, college age to late life, were motivated to learn about their brain and engage in virtual-training with coaching to improve their brain health. This effort intends to scale up to thousands, thus the pilot data, tested by an impending imaging pilot, will be utilized in ongoing machine learning (ML) algorithms to develop a precision brain health model. This pilot is a first step in scaling evidence-based brain health protocols to reach individuals and positively affect public health globally., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chapman, Fratantoni, Robertson, D'Esposito, Ling, Zientz, Vernon, Venza, Cook, Tate and Spence.)

Genomic surveillance of viral isolates during the 2013-2016 Ebola virus epidemic in Western Africa, the largest and most devastating filovirus outbreak on record, revealed several novel mutations. The responsible strain, named Makona, carries an A-to-V substitution at position 82 (A82V) in the glycoprotein (GP), which is associated with enhanced infectivity in vitro Here, we investigated the mechanistic basis for this enhancement as well as the interplay between A82V and a T-to-I substitution at residue 544 of GP, which also modulates infectivity in cell culture. We found that both 82V and 544I destabilize GP, with the residue at position 544 impacting overall stability, while 82V specifically destabilizes proteolytically cleaved GP. Both residues also promote faster kinetics of lipid mixing of the viral and host membranes in live cells, individually and in tandem, which correlates with faster times to fusion following colocalization with the viral receptor Niemann-Pick C1 (NPC1). Furthermore, GPs bearing 82V are more sensitive to proteolysis by cathepsin L (CatL), a key host factor for viral entry. Intriguingly, CatL processed 82V variant GPs to a novel product with a molecular weight of approximately 12,000 (12K), which we hypothesize corresponds to a form of GP that is pre-triggered for fusion. We thus propose a model in which 82V promotes more efficient GP processing by CatL, leading to faster viral fusion kinetics and higher levels of infectivity. IMPORTANCE The 2013-2016 outbreak of Ebola virus disease in West Africa demonstrated the potential for previously localized outbreaks to turn into regional, or even global, health emergencies. With over 28,000 cases and 11,000 confirmed deaths, this outbreak was over 50 times as large as any previously recorded. This outbreak also afforded the largest-ever collection of Ebola virus genomic sequence data, allowing new insights into viral transmission and evolution. Viral mutants arising during the outbreak have attracted attention for their potentially altered patterns of infectivity in cell culture, with potential, if unclear, implications for increased viral spread and/or virulence. Here, we report the properties of one such mutation in the viral glycoprotein, A82V, and its interplay with a previously described polymorphism at position 544. We show that mutations at both residues promote infection and fusion activation in cells but that A82V additionally leads to increased infectivity under cathepsin-limited conditions and the generation of a novel glycoprotein cleavage product., (Copyright © 2021 Fels et al.)

Introduction: Research shows that cognitive performance and emotional well-being can be significantly strengthened. A high-performance brain training protocol, Strategic Memory Advanced Reasoning Training (SMART), was developed by cognitive neuroscientists at The University of Texas at Dallas Center for BrainHealth based on 25-plus years of scientific study. Randomized controlled trials with various populations have shown that training and use of nine "SMART" strategies for processing information can improve cognitive performance and psychological health. However, the multi-week intensive training used in the laboratory is not practical for widespread use outside the laboratory. This article examines the efficacy of SMART when translated outside the laboratory to two populations (military/veterans and law enforcement) that received SMART in condensed time frames., Materials and Methods: In two translation studies with healthy military personnel and veterans, 425 participants received between 6 and 10 hours of SMART over 2 days. In a third translation study, 74 healthy police officers received 9 hours of SMART over 3 days. Training was conducted by clinicians who taught the nine "SMART" strategies related to three core areas-strategic attention, integrated reasoning, and innovation-to groups of up to 25 participants. In all three translation studies, cognitive performance and psychological health data were collected before and immediately following the training. In one of the military/veteran studies, psychological health data were also collected 1 and 4 months following the training., Results: In both translations to military personnel and veterans, there were improvements in the complex cognitive domains of integrated reasoning (P < .0001) and innovation (P < .0001) immediately after undergoing SMART. In the translation to police officers, there were improvements in the cognitive domains of innovation (P = .02) and strategic attention (P = .005). Participants in all three translations saw statistically significant improvements in self-reported symptoms of psychological health. The improvements continued among a subset of participants who responded to the later requests for information., Conclusions: The results of translating to these two populations provide evidence supporting the efficacy of SMART delivered in an abbreviated time frame. The improvements in two major domains of cognitive function demonstrate that strategies can be taught and immediately applied by those receiving the training. The immediate psychological health improvements may be transient; however, the continued improvements in psychological health observed in a subset of the participants suggest that benefits may be sustainable even at later intervals., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The neural mechanisms underlying motor impairment in multiple sclerosis (MS) remain unknown. Motor cortex dysfunction is implicated in blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies, but the role of neural-vascular coupling underlying BOLD changes remains unknown. We sought to independently measure the physiologic factors (i.e., cerebral blood flow (ΔCBF), cerebral metabolic rate of oxygen (ΔCMRO 2 ), and flow-metabolism coupling (ΔCBF/ΔCMRO 2 ), utilizing dual-echo calibrated fMRI (cfMRI) during a bilateral finger-tapping task. We utilized cfMRI to measure physiologic responses in 17 healthy volunteers and 32 MS patients (MSP) with and without motor impairment during a thumb-button-press task in thumb-related (task-central) and surrounding primary motor cortex (task-surround) regions of interest (ROIs). We observed significant ΔCBF and ΔCMRO 2 increases in all MSP compared to healthy volunteers in the task-central ROI and increased flow-metabolism coupling (ΔCBF/ΔCMRO 2 ) in the MSP without motor impairment. In the task-surround ROI, we observed decreases in ΔCBF and ΔCMRO 2 in MSP with motor impairment. Additionally, ΔCBF and ΔCMRO 2 responses in the task-surround ROI were associated with motor function and white matter damage in MSP. These results suggest an important role for task-surround recruitment in the primary motor cortex to maintain motor dexterity and its dependence on intact white matter microstructure and neural-vascular coupling.

Introduction: Prior Go/NoGo studies have localized specific regions and EEG spectra for which traditional approaches have distinguished between Go and NoGo conditions. A more detailed characterization of the spatial distribution and timing of the synchronization of frequency bands would contribute substantially to the clarification of neural mechanisms that underlie performance of the Go/NoGo task., Methods: The present study used a machine learning approach to learn the features that distinguish between ERSPs involved in selection and inhibition in a Go/NoGo task. A single-layer neural network classifier was used to predict task conditions for each subject to characterize ERSPs associated with Go versus NoGo trials., Results: The final classifier accurately identified individual task conditions at an overall rate of 92%, estimated by fivefold cross-validation. The detailed accounting of EEG time-frequency patterns localized to brain regions (i.e., thalamus, pre-SMA, orbitofrontal cortex, and superior parietal cortex) corroborates and also elaborates upon previous findings from fMRI and EEG studies, and expands the information about EEG power changes in multiple frequency bands (i.e., primarily theta power increase, alpha decreases, and beta increases and decreases) within these regions underlying the selection and inhibition processes engaged in the Go and NoGo trials., Conclusion: This time-frequency-based classifier extends previous spatiotemporal findings and provides information about neural mechanisms underlying selection and inhibition processes engaged in Go and NoGo trials, respectively. This neural network classifier can be used to assess time-frequency patterns from an individual subject and thus may offer insight into therapeutic uses of neuromodulation in neural dysfunction., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Cognitive slowing occurs in ~70% of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition. Loss of vascular compliance along the cerebrovascular tree would result in suboptimal vasodilation, neurovascular uncoupling, and cognitive slowing., Objective: To assess vascular compliance along the cerebrovascular tree and its relationship to MS-related cognition., Methods: We tested vascular compliance along the cerebrovascular tree by dividing cerebral cortex into nested layers. MS patients and healthy controls were scanned using a dual-echo functional magnetic resonance imaging (fMRI) sequence while they periodically inhaled room air and hypercapnic gas mixture. Cerebrovascular reactivity was calculated from both cerebral blood flow (arterial) and blood-oxygen-level-dependent signal (venous) increases per unit increase in end-tidal CO 2 ., Results: Arterial cerebrovascular reactivity changes along the cerebrovascular tree were reduced in cognitively slow MS compared to cognitively normal MS and healthy controls. These changes were fit to exponential functions, the decay constant (arterial compliance index; ACI) of which was associated with individual subjects' reaction time and predicted reaction time after controlling for disease processes., Conclusion: Such associations suggest prospects for utility of ACI in predicting future cognitive disturbances, monitoring cognitive deficiencies and therapeutic responses, and implicates neurovascular uncoupling as a mechanism of cognitive slowing in MS.

Background: The human brain has high energy requirements that continuously support healthy neuronal activity and cognition. A disruption in brain energy metabolism (BEM) may contribute to early neuropathological changes such as accumulation of β-amyloid and tau in vulnerable populations. One such population is amnestic mild cognitive impairment (aMCI) where some individuals are at risk for developing dementia, i.e. Alzheimer's disease (AD). Recent advances in imaging technology are providing new avenues to measure BEM accurately using 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7-Tesla. This study investigates whether a methodology using partial volume-coil 31P MRS at 7T over parieto-occipital lobes can accurately quantify high-energy phosphate and membrane phospholipid metabolites in aMCI. A secondary objective was to explore BEM and membrane phospholipid indices' correspondence with cognitive performance in domains of executive function (EF), memory, attention, and visuospatial skills in aMCI, a heterogeneous population., Methods: 19 aMCI participants enrolled in the study completed cognitive assessment and 31P MRS scan. BEM indices were measured using three energy indicators: energy reserve (PCr/t-ATP), energy consumption (intracellular&#95;Pi/t-ATP), and metabolic state (PCr/intracellular&#95;Pi) along with regulatory co-factors of BEM-intracellular Mg 2 + and pH; whereas the ratio of phosphomonoesters (PMEs) to phosphodiesters (PDEs) - membrane phospholipid indicator., Results: 31P MRS scan showed thirteen well-resolved peaks with precise quantification of the phosphorus metabolites at UHF. The higher BEM indices were associated with lower cognitive performance of memory [(energy reserve indicator: CVLT p = 0.004), (metabolic state indicator: CVLT p = 0.007)], executive function [(metabolic state indicator: TOSL ( p = 0.044)], and attention [(pH: selective auditory task, p = 0.044)]. The finding of an inverse relationship observed in the parieto-occipital lobes suggests an association between neuronal energy markers with cognition in aMCI., Conclusion: The significant contribution of this preliminary research was to establish the feasibility of utilizing a methodology at UHF to accurately measure high-energy phosphate and membrane phospholipid metabolites in a population with heterogeneous outcomes. This work offers a novel approach for future work to further elucidate early dementia biomarkers or precursors to the downstream accumulation of amyloid and tau using the combination of MRS-PET imaging modalities in AD., (Copyright © 2020 Das, Ren, Spence, Rackley and Chapman.)

Behavioral studies investigating fundamental cognitive abilities provide evidence that processing speed accounts for large proportions of performance variability between individuals. Processing speed decline is a hallmark feature of the cognitive disruption observed in healthy aging and in demyelinating diseases such as multiple sclerosis (MS), neuromyelitis optica, and Wilson's disease. Despite the wealth of evidence suggesting a central role for processing speed in cognitive decline, the neural mechanisms of this fundamental ability remain unknown. Intact neurovascular coupling, acute localized blood flow increases following neural activity, is essential for optimal neural function. We hypothesized that efficient coupling forms the neural basis of processing speed. Because MS features neural-glial-vascular system disruption, we used it as a model to test this hypothesis. To assess the integrity of the coupling system, we measured blood-oxygen-level-dependent (BOLD) signal in healthy controls (HCs) and MS patients using a 3T MRI scanner while they viewed radial checkerboards that flickered periodically at 8 ​Hz. To assess processing speed and cognitive function, we administered a battery of neuropsychological tests. While MS patients exhibited reduced ΔBOLD with reductions in processing speed, no such relationships were observed in HCs. To further investigate the mechanisms that underlie ΔBOLD-processing speed relationships, we assessed the physiologic components that constitute ΔBOLD signal (i.e., cerebral blood flow, ΔCBF; cerebral metabolic rate of oxygen, ΔCMRO 2 ; neurovascular coupling ratio) in speed-preserved and -impaired MS patients. While ΔCBF and ΔCMRO 2 showed no group-differences, the neurovascular coupling ratio was significantly reduced in speed-impaired MS patients compared to speed-preserved MS patients. Together, these results suggest that neurovascular uncoupling might underlie cognitive slowing in MS and might be the central pathogenic mechanism governing processing speed decline., Competing Interests: Declaration of competing interest DS, KW, MT, DA, YZ, HL, JS, MZ, BR report no disclosures related to the work presented here. DO received advisory and consulting fees from Celgene, EMD Serono, Genentech, Genzyme, and Novartis and research support from Biogen., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

To test the hypothesis that semantic processes are represented in multiple subsystems, we recorded electroencephalogram (EEG) as we elicited object memories using the modified Semantic Object Retrieval Test, during which an object feature, presented as a visual word [VW], an auditory word [AW], or a picture [Pic], was followed by a second feature always presented as a visual word. We performed both hypothesis-driven and data-driven analyses using event-related potentials (ERPs) time locked to the second stimulus. We replicated a previously reported left fronto-temporal ERP effect (750-1000 ms post-stimulus) in the VW task, and also found that this ERP component was only present during object memory retrieval in verbal (VW, AW) as opposed to non-verbal (Pic) stimulus types. We also found a right temporal ERP effect (850-1000 ms post-stimulus) that was present in auditory (AW) but not in visual (VW, Pic) stimulus types. In addition, we found an earlier left temporo-parietal ERP effect between 350 and 700 ms post-stimulus and a later midline parietal ERP effect between 700 and 1100 ms post-stimulus, present in all stimulus types, suggesting common neural mechanisms for object retrieval processes and object activation, respectively. These findings support multiple semantic subsystems that respond to varying stimulus modalities, and argue against an ultimate unitary amodal semantic analysis., (Published by Elsevier B.V.)

Background: Femoral nail bending is a rare complication of intramedullary (IM) fixation of femoral diaphyseal fractures. Published literature regarding this injury pattern has thus far been limited to case reports or case series, thus no universally accepted surgical treatment strategy has been developed., Methods: A systematic review was conducted using the Pubmed/MEDLINE and Scopus/EMBASE databases. A standardized template was used to extract data including author, year of publication, patient demographics, degree of angulation, mechanism of injury, time since initial procedure to reinjury, surgical treatment, and clinical outcomes. A case report from our institution was described as well., Results: 27 cases in 25 reports were included in the qualitative analysis. All of the patients were males, and the ages ranged from 17 to 66 (mean age = 27.8). The degree of deformity ranged from 18 to 85° (mean 35.6), most commonly in a varus or apex anterior orientation. The nail deformities were corrected via one of six general surgical techniques: full transection of the nail, partial sectioning and manual straightening, limited corticotomy or longitudinal bone window, straightening with the assistance of a plate and reduction clamps, closed manipulation, or extraction without the need for manipulation. The fractures were then most commonly treated with revision IM nail., Conclusions: The bent IM nail is a rare and challenging injury to treat. No one technique has been identified as "the gold standard" and each case must be approached with its unique characteristics in mind., Competing Interests: The authors have not conflicts of interest to declare., (© 2020 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Objectives: To determine (1) which factors are associated with the choice to perform an open reduction and (2) by adjusting for these factors, if the choice of reduction method is associated with reoperation., Design: Retrospective cohort study with radiograph and chart review., Setting: Twelve Level 1 North American trauma centers., Patients: Two hundred thirty-four adults 18-65 years of age with an isolated, displaced, OTA/AO type 31-B2 or type 31-B3 femoral neck fracture treated with internal fixation with minimum of 6-month follow-up or reoperation. Exclusion criteria were pathologic fractures, associated femoral head or shaft fractures, and primary arthroplasty., Intervention: Open or closed reduction technique during internal fixation., Main Outcome: Cox proportional hazard of reoperation adjusting for propensity score for open reduction based on injury, demographic, and medical factors. Reduction quality was assessed by 3 senior orthopaedic traumatologists as "acceptable" or "unacceptable" on AP and lateral postoperative radiographs., Results: Median follow-up was 1.5 years. One hundred six (45%) patients underwent open reduction. Reduction quality was not significantly affected by open versus closed approach (71% vs. 69% acceptable, P = 0.378). The propensity to receive an open reduction was associated with study center; younger age; male sex; no history of injection drug use, osteoporosis, or cerebrovascular disease; transcervical fracture location; posterior fracture comminution; and surgery within 12 hours. A total of 35 (33%) versus 28 (22%) reoperations occurred after open versus closed reduction (P = 0.056). Open reduction was associated with a 2.4-fold greater propensity-adjusted hazard of reoperation (95% confidence interval 1.3-4.4, P = 0.004). A total of 35 (15%) patients underwent subsequent total hip arthroplasty or hemiarthroplasty., Conclusions: Open reduction of displaced femoral neck fractures in nonelderly adults is associated with a greater hazard of reoperation without significantly improving reduction. Prospective randomized trials are indicated to confirm a causative effect of open versus closed reduction on outcomes after femoral neck fracture., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Interferon-induced transmembrane protein 3 (IFITM3) is a key interferon effector that broadly prevents infection by diverse viruses. However, the cellular factors that control IFITM3 homeostasis and antiviral activity have not been fully elucidated. Using site-specific photo-crosslinking and quantitative proteomic analysis, here we present the identification and functional characterization of VCP/p97 AAA-ATPase as a primary interaction partner of IFITM3. We show that IFITM3 ubiquitination at lysine 24 is crucial for VCP binding, trafficking, turnover, and engagement with incoming virus particles. Consistently, pharmacological inhibition of VCP/p97 ATPase activity leads to defective IFITM3 lysosomal sorting, turnover, and co-trafficking with virus particles. Our results showcase the utility of site-specific protein photo-crosslinking in mammalian cells and reveal VCP/p97 as a key cellular factor involved in IFITM3 trafficking and homeostasis., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Post-traumatic stress disorder (PTSD) is a debilitating condition that may develop after experiencing a traumatic event. Combat exposure increases an individual's chance of developing PTSD, making veterans especially susceptible to the disorder. PTSD is characterized by dysregulated emotional networks, memory deficits, and a hyperattentive response to perceived threatening stimuli. Recently, there have been a number of imaging studies that show structural and functional abnormalities associated with PTSD; however, there have been few studies utilizing electroencephalography (EEG). The goal of this study was to characterize **EEG brain dynamics in individuals with PTSD, in order to better understand the neurophysiological underpinnings of some of the salient features of PTSD, such as threat-processing bias. Veterans of Operation Enduring Freedom/Iraqi Freedom completed an implicit visual threat semantic memory recognition task with stimuli that varied on both category (animals, items, nature, and people) and feature (threatening and nonthreatening) membership, including trauma-related stimuli. Combat veterans with PTSD had slower reaction times for the threatening stimuli relative to the combat veterans without PTSD (VETC). There were trauma-specific effects in frontal regions, with theta band EEG power reductions for the threatening combat scenes in the PTSD patients compared to the VETC group. Additionally, a moderate negative correlation was observed between trauma-specific frontal theta power and hyperarousal symptoms as measured by clinically administered PTSD scale. These findings complement and extend current models of cortico-limbic dysfunction in PTSD. The moderate negative correlation between frontal theta power and hyperarousal endorsements suggests the utility of these measures as therapeutic markers of symptomatology in PTSD patients., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Chronic verbal retrieval deficits have been noted in traumatic brain injury (TBI), but no U.S. Food and Drug Administration-approved interventions are available. The present study investigated whether 10 sessions of 20 min of 1 mA anodal high-definition transcranial direct current stimulation (HD-tDCS) targeting pre-supplementary motor area/dorsal anterior cingulate cortex (preSMA/dACC) compared with sham HD-tDCS would improve verbal retrieval deficits in TBI patients. Improvements in verbal retrieval processes were observed up to 8 weeks post-treatment. Thus, potential dysfunction to verbal retrieval circuitry in TBI appears amenable to remediation through electromodulation with HD tDCS to the preSMA/dACC. Although further studies clarifying mechanisms by which tDCS brought about these improvements will likely inform refinements in the application of this therapeutic technique, the findings suggest the efficacy of using HD-tDCS to target other systems vulnerable to TBI to improve functioning.

Proximal femur fracture fixation with intramedullary nailing relies on stability at the fracture site and integrity of the fixation construct to achieve union. The biomechanics that dictate fracture site stability and implant stress depend on fracture type as well as implant features such as nail length, nail diameter, presence of distal fixation screws, and material composition of the implant. When deciding how to fix a fracture, surgeons have choices in these implant-related design variables. This study models all combinations of a range of implant variables for nine standard AO/OTA proximal femur fractures using finite element analysis. Under simulated maximum load during gait, the maximum stress in the implant and screws as well as interfragmentary motions at the fracture site in the axial and shear directions were computed. The results were separated by fracture type to show the influence of each design variable on measured biomechanical outcomes. Filling the reamed canal with the largest fitting nail diameter reduced axial and shear interfragmentary motion for all fracture types. Nail length was less predictive of shear interfragmentary motion for most simulated fracture types than other construct variables. Furthermore, gapping at the fracture site predisposed the construct to higher implant stresses and larger interfragmentary motions. Clinical significance: Biomechanical outcomes from this computational study can aid in surgical decision-making for optimizing hip fracture fixation with IM nailing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2358-2366, 2019., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Ebola virus (EBOV) causes highly lethal disease outbreaks against which no FDA-approved countermeasures are available. Although many host factors exploited by EBOV for cell entry have been identified, including host cell surface phosphatidylserine receptors, endosomal cysteine proteases, and the lysosomal cholesterol trafficking protein NPC1, key questions remain. Specifically, late entry steps culminating in viral membrane fusion remain enigmatic. Here, we investigated a set of glycoprotein (GP) mutants previously hypothesized to be entry defective and identified one mutation, R64A, that abolished infection with no apparent impact on GP expression, folding, or viral incorporation. R64A profoundly thermostabilized EBOV GP and rendered it highly resistant to proteolysis in vitro Forward-genetics and cell entry studies strongly suggested that R64A's effects on GP thermostability and proteolysis arrest viral entry at least at two distinct steps: the first upstream of NPC1 binding and the second at a late entry step downstream of fusion activation. Concordantly, toremifene, a small-molecule entry inhibitor previously shown to bind and destabilize GP, may selectively enhance the infectivity of viral particles bearing GP(R64A) at subinhibitory concentrations. R64A provides a valuable tool to further define the interplay between GP stability, proteolysis, and viral membrane fusion; to explore the rational design of stability-modulating antivirals; and to spur the development of next-generation Ebola virus vaccines with improved stability. IMPORTANCE Ebola virus is a medically relevant virus responsible for outbreaks of severe disease in western and central Africa, with mortality rates reaching as high as 90%. Despite considerable effort, there are currently no FDA-approved therapeutics or targeted interventions available, highlighting the need of development in this area. Host-cell invasion represents an attractive target for antivirals, and several drug candidates have been identified; however, our limited understanding of the complex viral entry process challenges the development of such entry-targeting drugs. Here, we report on a glycoprotein mutation that abrogates viral entry and provides insights into the final steps of this process. In addition, the hyperstabilized phenotype of this mutant makes it useful as a tool in the discovery and design of stability-modulating antivirals and next-generation vaccines against Ebola virus., (Copyright © 2019 Fels et al.)

Reproductive success in the eight founder strains of the Collaborative Cross (CC) was measured using a diallel-mating scheme. Over a 48-month period we generated 4,448 litters, and provided 24,782 weaned pups for use in 16 different published experiments. We identified factors that affect the average litter size in a cross by estimating the overall contribution of parent-of-origin, heterosis, inbred, and epistatic effects using a Bayesian zero-truncated overdispersed Poisson mixed model. The phenotypic variance of litter size has a substantial contribution (82%) from unexplained and environmental sources, but no detectable effect of seasonality. Most of the explained variance was due to additive effects (9.2%) and parental sex (maternal vs. paternal strain; 5.8%), with epistasis accounting for 3.4%. Within the parental effects, the effect of the dam's strain explained more than the sire's strain (13.2% vs. 1.8%), and the dam's strain effects account for 74.2% of total variation explained. Dams from strains C57BL/6J and NOD/ShiLtJ increased the expected litter size by a mean of 1.66 and 1.79 pups, whereas dams from strains WSB/EiJ, PWK/PhJ, and CAST/EiJ reduced expected litter size by a mean of 1.51, 0.81, and 0.90 pups. Finally, there was no strong evidence for strain-specific effects on sex ratio distortion. Overall, these results demonstrate that strains vary substantially in their reproductive ability depending on their genetic background, and that litter size is largely determined by dam's strain rather than sire's strain effects, as expected. This analysis adds to our understanding of factors that influence litter size in mammals, and also helps to explain breeding successes and failures in the extinct lines and surviving CC strains., (Copyright © 2019 Shorter et al.)

The hemodynamic response function (HRF), a model of brain blood-flow changes in response to neural activity, reflects communication between neurons and the vasculature that supplies these neurons in part by means of glial cell intermediaries (e.g., astrocytes). Intact neural-vascular communication might play a central role in optimal cognitive performance. This hypothesis can be tested by comparing healthy individuals to those with known white-matter damage and impaired performance, as seen in Multiple Sclerosis (MS). Glial cell intermediaries facilitate the ability of neurons to adequately convey metabolic needs to cerebral vasculature for sufficient oxygen and nutrient perfusion. In this study, we isolated measurements of the HRF that could quantify the extent to which white-matter affects neural-vascular coupling and cognitive performance. HRFs were modeled from multiple brain regions during multiple cognitive tasks using piecewise cubic spline functions, an approach that minimized assumptions regarding HRF shape that may not be valid for diseased populations, and were characterized using two shape metrics (peak amplitude and time-to-peak). Peak amplitude was reduced, and time-to-peak was longer, in MS patients relative to healthy controls. Faster time-to-peak was predicted by faster reaction time, suggesting an important role for vasodilatory speed in the physiology underlying processing speed. These results support the hypothesis that intact neural-glial-vascular communication underlies optimal neural and cognitive functioning., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Transcranial direct current stimulation (tDCS), a non-invasive stimulation, represents a potential intervention to enhance cognition across clinical populations including Alzheimer's disease and mild cognitive impairment (MCI). This randomized clinical trial in MCI investigated the effects of anodal tDCS (a-tDCS) delivered to left inferior frontal gyrus (IFG) combined with gist-reasoning training (SMART) versus sham tDCS (s-tDCS) plus SMART on measures of cognitive and neural changes in resting cerebral blood flow (rCBF). We were also interested in SMART effects on cognitive performance regardless of the tDCS group., Methods: Twenty-two MCI participants, who completed the baseline cognitive assessment (T1), were randomized into one of two groups: a-tDCS + SMART and s-tDCS + SMART. Of which, 20 participants completed resting pCASL MRI scan to measure rCBF. Eight SMART sessions were administered over 4 weeks with a-tDCS or s-tDCS stimulation for 20 min before each session. Participants were assessed immediately (T2) and 3-months after training (T3)., Results: Significant group × time interactions showed cognitive gains at T2 in executive function (EF) measure of inhibition [DKEFS- Color word ( p = 0.047)], innovation [TOSL ( p = 0.01)] and on episodic memory [TOSL ( p = 0.048)] in s-tDCS + SMART but not in a-tDCS + SMART group. Nonetheless, the gains did not persist for 3 months (T3) after the training. A voxel-based analysis showed significant increase in regional rCBF in the right middle frontal cortex (MFC) (cluster-wise p = 0.05, k = 1,168 mm 3 ) in a-tDCS + SMART compared to s-tDCS + SMART. No significant relationship was observed between the increased CBF with cognition. Irrespective of group, the combined MCI showed gains at T2 in EF of conceptual reasoning [DKEFS card sort ( p = 0.033)] and category fluency [COWAT ( p = 0.055)], along with gains at T3 in EF of verbal fluency [COWAT ( p = 0.009)]., Conclusion: One intriguing finding is a-tDCS to left IFG plus SMART increased blood flow to right MFC, however, the stimulation seemingly blocked cognitive benefits of SMART on EF (inhibition and innovation) and episodic memory compared to s-tDCS + SMART group. Although the sample size is small, this paper contributes to growing evidence that cognitive training provides a way to significantly enhance cognitive performance in adults showing memory loss, where the role of a-tDCS in augmenting these effects need further study.

Functional magnetic resonance imaging (fMRI) has been used to infer age-differences in neural activity from the hemodynamic response function (HRF) that characterizes the blood-oxygen-level-dependent (BOLD) signal over time. BOLD literature in healthy aging lacks consensus in age-related HRF changes, the nature of those changes, and their implications for measurement of age differences in brain function. Between-study discrepancies could be due to small sample sizes, analysis techniques, and/or physiologic mechanisms. We hypothesize that, with large sample sizes and minimal analysis assumptions, age-related changes in HRF parameters could reflect alterations in one or more components of the neural-vascular coupling system. To assess HRF changes in healthy aging, we analyzed the large population-derived dataset from the Cambridge Center for Aging and Neuroscience (CamCAN) study (Shafto et al., 2014). During scanning, 74 younger (18-30 years of age) and 173 older participants (54-74 years of age) viewed two checkerboards to the left and right of a central fixation point, simultaneously heard a binaural tone, and responded via right index finger button-press. To assess differences in the shape of the HRF between younger and older groups, HRFs were estimated using FMRIB's Linear Optimal Basis Sets (FLOBS) to minimize a priori shape assumptions. Group mean HRFs were different between younger and older groups in auditory, visual, and motor cortices. Specifically, we observed increased time-to-peak and decreased peak amplitude in older compared to younger adults in auditory, visual, and motor cortices. Changes in the shape and timing of the HRF in healthy aging, in the absence of performance differences, support our hypothesis of age-related changes in the neural-vascular coupling system beyond neural activity alone. More precise interpretations of HRF age-differences can be formulated once these physiologic factors are disentangled and measured separately., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) have emerged as important innate immune effectors that prevent diverse virus infections in vertebrates. However, the cellular mechanisms and live-cell imaging of these small membrane proteins have been challenging to evaluate during viral entry of mammalian cells. Using CRISPR-Cas9-mediated IFITM-mutant cell lines, we demonstrate that human IFITM1, IFITM2 and IFITM3 act cooperatively and function in a dose-dependent fashion in interferon-stimulated cells. Through site-specific fluorophore tagging and live-cell imaging studies, we show that IFITM3 is on endocytic vesicles that fuse with incoming virus particles and enhances the trafficking of this pathogenic cargo to lysosomes. IFITM3 trafficking is specific to restricted viruses, requires S-palmitoylation and is abrogated with loss-of-function mutants. The site-specific protein labeling and live-cell imaging approaches described here should facilitate the functional analysis of host factors involved in pathogen restriction as well as their mechanisms of regulation.

Our team previously reported event-related potential (ERP) and hyperarousal patterns from a study of one construction battalion of the U.S. Naval Reserve who served during the 1991 Persian Gulf War. We sought to replicate these findings in a sample that was more representative of the entire Gulf War-era veteran population, including male and female participants from four branches of the military. We collected ERP data from 40 veterans meeting Haley criteria for Gulf War syndromes 1-3 and from 22 matched Gulf War veteran controls while they performed an auditory oddball task. Reports of hyperarousal from the ill veterans were significantly greater than those from the control veterans, and P1 amplitudes in Syndromes 2 and 3 were significantly higher than P1 amplitudes in Syndrome 1, replicating our previous findings. Many of the contributors to the generation of the P1 potential are also involved in the regulation of arousal and are modulated by cholinergic and dopaminergic systems-two systems whose dysfunction has been implicated in Gulf War illness. These differences among the three syndrome groups where their means were on either side of controls is a replication of our previous ERP study and is consistent with previous imaging studies of this population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To investigate differences in inhibitory control and processing speed over the life span, participants in 7- to 8-, 10- to 11-, 12- to 15-, 18- to 25-, and 54- to 80-year-old age cohorts completed a Go/No-Go task requiring varying levels of semantic categorization. Discriminant function analysis of correct rejection rates (CRRs), hit rates (HRs), and reaction times (RTs) revealed a function on which CRR loaded positively and RT loaded negatively, across categorization levels. Scores increased from youngest to the younger adult cohort and decreased for the older adult cohort. On a second function, CRR and RT loaded positively and HR loaded negatively across categorization levels. Scores were highest for the older adult cohort and higher for the youngest cohort than for the younger adult cohort. The results suggest change along 2 dimensions might underlie cognitive development: (a) combined increased inhibitory control and processing speed and (b) combined increased speed and decreased biased responding for better inhibitory control. In addition, 2 dimensions might underlie senescence: (a) combined decreased inhibitory control and processing speed and (b) combined decreased speed and increased biased responding for better inhibitory control. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Factors that contribute to overcoming decision-making biases in later life pose an important investigational question given the increasing older adult population. Limited empirical evidence exists and the literature remains equivocal of whether increasing age is associated with elevated susceptibility to decision-making biases such as framing effects. Research into the individual differences contributing to decision-making ability may offer better understanding of the influence of age in decision-making ability. Changes in cognition underlying decision-making have been shown with increased age and may contribute to individual variability in decision-making abilities. This study had three aims; (1) to understand the influence of age on susceptibility to decision-making biases as measured by framing effects across a large, continuous age range; (2) to examine influence of cognitive abilities that change with age; and (3) to understand the influence of individual factors such as gender and education on susceptibility to framing effects. 200 individuals (28-79 years of age) were tested on a large battery of cognitive measures in the domains of executive function, memory and complex attention. Findings from this study demonstrated that cognitive abilities such as strategic control and delayed memory better predicted susceptibility to framing biases than age. The current findings demonstrate that age may not be as influential a factor in decision-making as cognitive ability and cognitive reserve. These findings motivate future studies to better characterize cognitive ability to determine decision-making susceptibilities in aging populations.